The excipient news blog - shared with the Linkedin pharma excipients group! Pharmaceutical excipients (inactive ingredients) play a major role in development and production of pharmaceutical dosage forms - we publish up to date information on all aspects of excipients.

Excipienttalk - Latest news on pharmaceutical excipients

Recent advances in the design of polymeric microneedles for transdermal drug delivery and biosensing

Microneedles is an efficient and minimally-invasive approach of transdermal drug delivery and extraction of skin interstitial fluid. Compared to solid microneedles made of silicon, metals and ceramics, polymeric microneedles have attracted extensive attentions due to their excellent biocompatibility, biodegradability and nontoxicity. They are ease to fabricate in large scale and load drugs with high amounts. More importantly, polymers with different degradation profiles, swelling properties, and responses to biological/physical stimulis can be employed to fabricate polymeric microneedles with different mechanical properties and performance. This review provides the guideline of the selection of polymers and the corresponding fabrication methods for the polymeric microneedles while summarizing their recent application in drug delivery and fluid extraction. It should be noted that although polymeric microneedles can achieve efficient transdermal delivery of drugs, their wide applications were limited by their unsatisfactory transdermal therapeutic efficiency. Delivery of nanomedicines that incorporates drugs into functional nanoparticles/capsules can address this problem and thus may be an interesting direction in the future.

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Structure, functionality and applications of debranched starch: A review

Background

Starchy products have been widely used in the food, paper, textile, plastic, cosmetics, adhesives, and pharmaceutical industries. To meet specific requirements of their applications, different modification techniques, such as physical, chemical, and enzymatic methods, have been employed to enhance or inhibit their inherent properties or to endow specific properties of starch.

 

Scope and approach

Debranched starch (DBS), modified by pullulanase or isoamylase, acquires remarkable new properties and functionality, as a result of the generation of linear short chains released from amylopectin. In this review, the structure, functionality, and applications of DBS are discussed. The effects of debranching on the granule morphology, molecular composition, crystalline and helical structures are considered. Functionality, like gelatinization, hydrogel formation, and in vitro digestibility, is discussed. This paper also highlights promising applications of DBS, e.g., as tableting excipients, fat replacer, and as coating materials for ready-to-eat cereals.

 

Key findings and conclusions

DBS is an excellent functional material, with promising applications attributed to its gel forming and recrystallization properties. Linear short chains released from amylopectin during debranching endow DBS with increased mobility and facilitate molecule alignment and aggregation, leading to the formation of gel networks and crystalline structures. A combination of gel network and crystalline structure controls the formation of SDS/RS. The applications of DBS as tableting excipients, fat replacer, and coating materials for ready-to-eat cereals are mainly attributed to its gelling properties. Molecular inclusion drives the formation of inclusion complexes, self-assembling spheroids, and DBS-based nanoparticles.

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Formulation and Evaluation of Bosentan Solid Dispersion

Aim: The therapeutic efficiency of a formulation will depend on various crucial parameters such as solubility of the drug, stability of the compound, excipients used in the formulation of finished dosage form, and the manufacturing technology used for the fabrication of finished dosage form. This research work is an attempt to enhance the solubility and dissolution rate by fabricating solid dispersion (SD) of the bosentan using hydrophilic polymers, soluplus, and kollidon VA 64. SDs of different drug: Polymer ratios were prepared using both the polymers separately (1:1, 1:2, 1:3, and 1:4). The SDs obtained were characterized by differential scanning calorimetry and X-ray powder diffraction analysis. Material and Methods: Bosentan, soluplus, and kollidon VA 64 were the important materials and hot-melt extrusion (HME) is the equipment used for manufacturing of SD. Results and Discussion: The studies shown that the crystalline drug was successfully converted to amorphous form by fabricating SD using HME. The SDs were further evaluated by performing dissolution studies, and a comparison was made between the pure drug and the SDs. The SD showing better release profile in water as dissolution medium was further evaluated. SD2 shown marked increase in the dissolution rate when compared with the pure drug dissolution. Conclusion: SD fabricated using soluplus as a polymer shown better release profile when compared with SDs fabricated with kollidon VA 64.

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Formulation and Evaluation of Immediate Release Telmisartan Tablets using Hydrophilic Polymers

Aim: Telmisartan is an anti-hypertensive drug under the class of angiotensin II receptor blocker. The aim is to formulate and evaluated immediate release telmisartan tablets using hydrophilic polymers. Materials and Method: The hydrophilic polymers are polyethylene glycol 4000 (PEG-4000) and PEG-6000. Solid dispersion is prepared with polymers with different ratios 1:0.5, 1:1, 1:2 and formulated into tablets. Formulations were characterized for drug content studies, drug release studies, and drug-polymer interactions using Fourier transform infrared spectroscopy (FTIR) spectrum. Results and Discussions: Formulation containing 1:2 ratio of drug: PEG-6000 showed the best release with a cumulative release of 99.67% as compared to 74.36% for the PEG- 4000. The FTIR studies showed that there is no interaction between the drug and polymer. Conclusion: Based evaluation of different parameters it was concluded that formulation of immediate release tablets of telmisartan was successfully done and F6 shows 100% at 60 min.

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An innovative method for the preparation of high API-loaded hollow spherical granules for use in controlled-release formulation

Abstract

The aim of this study was to prepare controlled-release (CR) granules with suitable particle strength, flowability, particle size distribution (PSD) and density characteristics for blending with other excipients. We also wanted these CR granules to contain large quantities of active pharmaceutical ingredient (API). A high shear mixer was used to mix an API with various polymers at various feed ratios, and the resulting granulated materials were sprayed with solvent. The wet granules were dried using a fluidized bed dryer to give CR granules. The API content of the granules was determined to be 95%wt. The granules were found to be spherical in shape with smooth surfaces by scanning electron microscopy. The inner structure of each granule was determined to be hollow by X-ray computed tomography, highlighting the unusual mechanism of this granulation process. The PSD of the granules was found to be dependent on that of the constituent polymer, and a narrow PSD was obtained by adjusting the PSD of the polymer. The dissolution profile of the granules was also dependent on the constituent polymer. Taken together, these results show that we have successfully developed a new manufacturing technology for the simple and low-cost preparation of ideal CR granules.

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Modeling and analysis of dissolution of paracetamol/Eudragit® formulations

Abstract

In this work, amorphous paracetamol/Eudragit® formulations for four Eudragit® (polymeric excipients) were prepared by spray drying technique. The simultaneous dissolution kinetics of paracetamol and Eudragit® from these formulations were measured as function of pH in vitro using a rotating disk system (USP II). Paracetamol dissolution mechanisms were analyzed by comparing the dissolution rates of paracetamol and excipient. It was found that a controlled paracetamol dissolution was achieved from Eudragit® L 100-55 and Eudragit® E PO formulations at pH 5.0, 6.5, and 7.2. Furthermore, a controlled paracetamol dissolution was also achieved from Eudragit® L 100 formulations at pH 6.51 and 7.27 as well as from Eudragit® S 100 formulations at pH 7.27. Paracetamol dissolution rates were controlled by both paracetamol and excipient from Eudragit® L 100 and S 100 formulations at other pH values. Moreover, a chemical-potential-gradient model combined with PC-SAFT was used to model the dissolution kinetics of PARA from these formulations in good accordance with the experimental data.

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Correlation between calculated molecular descriptors of excipient amino acids and experimentally observed thermal stability of lysozyme

Abstract

A quantitative structure-property relationship (QSPR) between protein stability and the physicochemical properties of excipients was investigated to enable a more rational choice of stabilizing excipients than prior knowledge. The thermal transition temperature and aggregation time were determined for lysozyme in combination with 13 different amino acids using high throughput fluorescence spectroscopy and kinetic static light scattering measurements. On the theoretical side, around 200 2D and 3D molecular descriptors were calculated based on the amino acids’ chemical structure. Multivariate data analysis was applied to correlate the descriptors with the experimental results. It was possible to identify descriptors, i.e. amino acids properties, with a positive influence on either transition temperature or aggregation onset time, or both. A high number of hydrogen bond acceptor moieties was the most prominent stabilizing factor for both responses, whereas hydrophilic surface properties and high molecular mass density mostly had a positive influence on the unfolding temperature. A high partition coefficient (logP(o/w)) was identified as the most prominent destabilizing factor for both responses. The QSPR shows good correlation between calculated molecular descriptors and the measured stabilizing effect of amino acids on lysozyme.

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Budenheim site GMP certified for phosphate excipients

Chemische Fabrik Budenheim site receives EXCiPACT GMP Certification as pharmaceutical excipient suppliers

 

Speciality products and phosphates company, Budenheim, has received an GMP/GDP Certificate for pharmaceutical excipients produced at its Chemische Fabrik site in Germany.

The certificate demonstrates that the site manufactures pharmaceutical excipients according to the EXCiPACT Good Manufacturing Practices (GMP) and Good Distribution Practices (GDP) Certification Standards.

Its scope covers manufacturing, testing, storage and distribution of sodium, magnesium and calcium phosphates for use as pharmaceutical excipients.

The certificate was granted by SGS, one of EXCIPACT’s internationally recognised Certification Bodies.

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Physicochemical Characterization and Dissolution Study of Solid Dispersion Tablet of Azithromycin

Aim: To increase the solubility of azithromycin by formulating solid dispersion (SD) and then SD tablets (SDT) were prepared from the best formulation of SDs. Material and Methods: SDs were prepared using polyethylene glycol 6000 and β-cyclodextrin (β-CD) by solvent evaporation method. To investigate drug-excipient interaction and for selection of suitable excipient for formulation differential scanning calorimetry study was done, and each excipient was selected for formulation development only if it showed compatible results. Results and Discussion: Tablets were prepared by direct compression technique using hydroxypropylmethylcellulose (HPMC)-K 100 and guar gum in different concentrations. SDs were evaluated for drug content, in vitro dissolution profiles, and developed SDT were evaluated for various pharmaceutical characteristics, viz., hardness, friability, weight variation, thickness, drug content, and in vitro drug release. Conclusion: Study indicates that among various formulations SDT of azithromycin: β-CD (1:2) complexes prepared using HPMC and guar gum in 1:4 combination showed maximum drug release.

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Vapour-phase method in the synthesis of polymer-ibuprofen sodium-silica gel composites

Abstract

The study discusses the synthesis of polymer-silica composites comprising water soluble drug (ibuprofen sodium, IBS). The polymers selected for this study were poly(TRIM) and poly(HEMA-co-TRIM) produced in the form of permanently porous beads via the suspension-emulsion polymerization method. The acid and base set ternary composites were prepared by the saturation of the solid dispersions of drug (poly(TRIM)-IBS and/or poly(HEMA-co-TRIM)-IBS) with TEOS, and followed by their exposition to the vapour mixture of water and ammonia, or water and hydrochloric acid, at autogenous pressure. The conducted analyses reveal that the internal structure and total porosity of the resulting composites strongly depend on the catalyst which was used for silica precursor gelation. The parameters characterizing the porosity of both of the acid set composites are much lower than the parameters of the base set composites. Moreover, the basic catalyst supplied in the vapour phase does not affect the ibuprofen sodium molecules, whereas the acid one causes transformation of the ibuprofen sodium into the sodium chloride and a derivative of propanoic acid, which is poorly water soluble. The release profiles of ibuprofen sodium from composites demonstrate that there are differences in the rate and efficiency of drug desorption from them. They are mainly affected by the chemical character of the polymeric carrier but are also associated with the restricted swelling of the composites in the buffer solution after precipitation of silica gel.

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pH responsive controlled release of anti-cancer hydrophobic drugs from sodium alginate and hydroxyapatite bi-coated iron oxide nanoparticles

Abstract

Developing a drug carrier system which could perform targeted and controlled release over a period of time is utmost concern in the pharmaceutical industry. This is more relevant when designing drug carriers for poorly water soluble drug molecules such as curcumin and 6-gingerol. Development of a drug carrier system which could overcome these limitations and perform controlled and targeted drug delivery is beneficial. This study describes a promising approach for the design of novel pH sensitive sodium alginate, hydroxyapatite bilayer coated iron oxide nanoparticle composite (IONP/HAp-NaAlg) via the co-precipitation approach. This system consists of a magnetic core for targeting and a NaAlg/ HAp coating on the surface to accommodate the drug molecules. The nanocomposite was characterized using FT-IR spectroscopy, X-ray diffraction, scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis. The loading efficiency and loading capacity of curcumin and 6-gingerol were examined. The in-vitro drug releasing behavior of curcumin and 6-gingerol was studied at pH 7.4 and pH 5.3 over a period of seven days at 37 °C. The mechanism of drug release from the nanocomposite of each situation was studied using kinetic models and the results implied that, the release is typically via diffusion and a higher release was observed at pH 5.3. This bilayer coated system can be recognized as a potential drug delivery system for the purpose of curcumin and 6-gingerol release in targeted and controlled manner to treat diseases such as cancer.

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The application prospects and development trends of orally disintegrating tablets to dogs

ABSTRACT:

Orally disintegrating tablets (ODTs) disintegrate rapidly in the mouth in seconds when placed at the tongue. The introduction of ODTs for dogs can address many needs, ranging from convenient dosing for dogs with dysphagia to extending life cycle of drugs. Now, different technologies are widely combined for developing ODTs. The combination makes ODTs have more properties, obtaining orally disintegrating sustained release tablets or orally disintegrating enteric tablets or enhancing the dissolution rate and bioavailability of poorly water-soluble drugs and so on. The aim of this article is to give a comprehensive prospect to the application of ODTs to dogs, including ideal properties of drugs, indications of ODTs, considerations in developing ODTs and development trends of ODTs for dogs.

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Biogrund Film Coating Excellence - Newsletter Spring 2017

Highlights on

  • HME Cleaner Plus (GMP) - Easy cleaning of hot melt extrusion
  • BonuCel® - Rapid success with an easy-to-use hypromellose for pharmaceutical, food & personal care applications
  • Coating & Tabletting Workshop @ BIOGRUND
  • Vitafoods Europe, Geneva, 9 - 11 May 2017
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Formulation approaches to pediatric oral drug delivery: benefits and limitations of current platforms

Abstract

 

Introduction: Most conventional drug delivery systems are not acceptable for pediatric patients as they differ in their developmental status and dosing requirements from other subsets of the population. Technology platforms are required to aid the development of age-appropriate medicines to maximize patient acceptability while maintaining safety, efficacy, accessibility and affordability.

Areas covered: The current approaches and novel developments in the field of age-appropriate drug delivery for pediatric patients are critically discussed including patient-centric formulations, administration devices and packaging systems.

Expert opinion: Despite the incentives provided by recent regulatory modifications and the efforts of formulation scientists, there is still a need for implementation of pharmaceutical technologies that enable the manufacture of licensed age-appropriate formulations. Harmonization of endeavors from regulators, industry and academia by sharing learning associated with data obtained from pediatric investigation plans, product development pathways and scientific projects would be the way forward to speed up bench-to-market age appropriate formulation development. A collaborative approach will benefit not only pediatrics, but other patient populations such as geriatrics would also benefit from an accelerated patient-centric approach to drug delivery.

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Rational excipient selection for co-amorphous formulations

ABSTRACT

Introduction: For almost two decades there has been intense debate about whether the amorphous solid state form could resolve the solubility problems and subsequent bioavailability issues of many small molecule drugs. Since the amorphous form is a high energy and unstable state of solid matter, any material in that form requires stabilization.

Areas covered: This review examines the technologies being exploited to stabilize the amorphous state in co-amorphous formulations. The review emphasizes the importance of the appropriate selection criteria of stabilizing excipient and focuses on the mechanisms of stabilization.

Expert opinion: An extensive literature review has revealed that the current research seeking to achieve stabilization of an amorphous form tends to be conducted on a case-by-case basis. This kind of approach is very inefficient since it can rarely be transferred to other cases. The greatest weakness in the selection of stabilizing excipient for co-amorphous formulations is that modern computational tools have rarely been utilized as a predictive tool in the selection of the excipient. It is evident that more research needs to be done to study larger datasets with modern in silico tools, chemometrics and advanced statistical tools to achieve a more predictive, and systematic approach for the screening of stabilizing excipients to be incorporated into co-amorphous formulations.

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Dry powder inhalation: past, present and future

Abstract

 

Introduction: Early dry powder inhalers (DPIs) were designed for low drug doses in asthma and COPD therapy. Nearly all concepts contained carrier-based formulations and lacked efficient dispersion principles. Therefore, particle engineering and powder processing are increasingly applied to achieve acceptable lung deposition with these poorly designed inhalers.

 

Areas covered: The consequences of the choices made for early DPI development with respect of efficacy, production costs and safety and the tremendous amount of energy put into understanding and controlling the dispersion performance of adhesive mixtures are discussed. Also newly developed particle manufacturing and powder formulation processes are presented as well as the challenges, objectives, and new tools available for future DPI design.

 

Expert opinion: Improved inhaler design is desired to make DPIs for future applications cost-effective and safe. With an increasing interest in high dose drug delivery, vaccination and systemic delivery via the lungs, innovative formulation technologies alone may not be sufficient. Safety is served by increasing patient adherence to the therapy, minimizing the use of unnecessary excipients and designing simple and self-intuitive inhalers, which give good feedback to the patient about the inhalation maneuver. For some applications, like vaccination and delivery of hygroscopic formulations, disposable inhalers may be preferred.

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Physical modification and characterization of starch using pregelatinization and co- process of various tubers from Yogyakarta as an excipient

Abstract. Starch is an economical excipient that is used in oral dosage form. It has poor compressibility and flowability. Pregelatinization and co-process as a physical modification technique have been conducted widely; nevertheless, the single modification shows a limitation. This study aims to assess and characterize the starch result of the modification of various tubers by a combination of modification methods. The starches from various tubers were extracted by sedimentation. Starch pregelatinization was conducted by manufacturing a starch suspension and was heated at 55oC for 70 minutes, and then it was mixed using concentrations HPMC k15 of 2, 3, and 4% (w/w) of the starch weight. The evaluations that were conducted are general identification, amylose concentration, physical properties, and physicochemical identification. The obtained starch of the extraction was 10-18% of the fresh tubers, with the concentration of amylose around 21-37%. The shape and particle size of the starch affected the amylose concentration. The starch modification showed an improvement of the granules physical properties by addition of HPMC. The amylose concentration of yam starch was 37.60% and showed the optimum modification result in the addition of HPMC 4%. There were no changes in the physicochemical properties of the result of IR and X-ray diffraction analysis. The melting point of yam starch-HPMC 4% was 151.24oC with reduction of the maximum weight at 328.52oC. This study indicated that the yam starch has the highest amylose concentration with optimum granules result of the modification in addition of HPMC 4% that could be used as an alternative excipient.

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Critical Material Attributes of Strip Films Loaded With Poorly Water-Soluble Drug Nanoparticles: II. Impact of Polymer Molecular Weigh

Abstract

Recent work established polymer strip films as a robust platform for delivery of poorly water-soluble drug particles. However, a simple means of manipulating rate of drug release from films with minimal impact on film mechanical properties has yet to be demonstrated. This study explores the impact of film-forming polymer molecular weight (MW) and concentration on properties of polymer films loaded with poorly water-soluble drug nanoparticles. Nanoparticles of griseofulvin, a model Biopharmaceutics Classification System class II drug, were prepared in aqueous suspension via wet stirred media milling. Aqueous solutions of 3 viscosity grades of hydroxypropyl methylcellulose (14, 21, and 88 kDa) at 3 viscosity levels (∼9500, ∼12,000, and ∼22,000 cP) were mixed with drug suspension, cast, and dried to produce films containing griseofulvin nanoparticles. Few differences in film tensile strength or elongation at break were observed between films within each viscosity level regardless of polymer MW despite requiring up to double the time to achieve 100% drug release. This suggests film-forming polymer MW can be used to manipulate drug release with little impact on film mechanical properties by matching polymer solution viscosity. In addition, changing polymer MW and concentration had no negative impact on drug content uniformity or nanoparticle redispersibility.

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Formulation and evaluation of nasal in situ gel of phenylephrine hydrochloride

Abstract

In situ gel drug delivery systems are in solution form before administration but once administered, undergo gelation in situ, to form a gel. In the present study nasal in situ gel of Phenylephrine hydrochloride was prepared for the treatment of nasal infections to provide sustained release of drug and to attain site specific action. Carbopol 934 was used as a pH triggered polymer and Poloxamer 188 was used as thermo sensitive agent. Different formulations were prepared by varying the concentrations of Carbopol 934 and Poloxamer 188 polymers in combination with Hydroxylpropyl Methylcellulose (HPMC), HPMC E5LV, HPMC E15LV, and HPMC E50 LV as viscosity enhancing agents. These formulations were evaluated for parameters like drug excipient compatibility, pH, drug content, gelation temperature, viscosity, in vitro drug release, mucoadhesion, ex vivo permeation and stability studies. FTIR study revealed that there was no interaction between drug and polymer. pH of all the formulations were found to be in the range of 5.4-6.2 and the drug content for all the prepared formulations was found to be in the range of 94%-99%. The results of in vitro drug release and mucoadhesive strength indicated that the optimized formulation F15 and F18 is the most successful formulations of the study, exhibited a sustained drug release of in 77.8% in 6 hours and 70.8% in 8 hours with a mucoadhesive strength of 3124.64 and 3167.76 dyne/cm2. From the results it is concluded that Phenylephrine hydrochloride nasal in situ gel produces prolonged and site specific drug delivery for the treatment of respiratory tract infections especially for sinusitis and bronchitis.

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Formulation and Evaluation of Oro-Dispersible Tablets Using Modified Polysaccharides

Abstract: Orodispersible tablets (ODT) of levocetirizine was prepared using natural polysaccharides ipomoea batatas starch, amorphophallus campanulatus starch and their modified form by direct compression method and evaluated for their superdisintegrant activity. Levocetirizine dihydrochloride was used as a model drug. The prepared formulations were compared with synthetic superdisintegrants such as crosspovidone and diluent Ludiflash for disintegration and other ODT parameters. FTIR study indicated no interaction between drug and excipients. Precompression parameters, studied for all the formulations were found to be satisfactory. Different concentrations of 2.5%, 5, 7.5% and 10% of modified and unmodified forms of both starches were studied for the improvement in the ODT parameters. The formulations LISN (10%), LISM (10%) (LIS-levocetirizine dihydrochloride+ ipomoea batatas starch; N-Natural; M-Modified) and LASN (10%), LASM (10%) (LAS-levocetirizine dihydrochloride+amorphophallus campanulatus starch; N-Natural; M- modified) of both the starches showed better DT than lower concentrations. Synthetic superdisintegrant crosspovidone was compared with formulations of natural superdisintegrants. The formulation containing crospovidone 5% concentration showed better DT of 32 seconds compared to natural superdisintegrants, and was used for further comparison of modified polysaccharides. The tablets prepared with Ludiflash as diluent without crospovidone, showed no significant difference in disintegration time. The formulation LASMLU (LAS-Levocetirizine dihydrochloride + amorphophallus campanulatus starch; M-Modified; Lu-Ludiflash) showed 95% of drug release compared to other formulations. The release profile of 10% of modified amorphophallus campanulatus starch LASM or Ludiflash (LASMLU) formulations did not show any significant difference in release profile. Hence in conclusion starch citrate, a new modified starch at 10% or at 5% concentration with crosspovidone with or without Ludiflash as diluent can be used as superdisintegrant for the preparation of orodispersible tablets.

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Work plan for the CHMP Excipients Drafting Group (ExcpDG) for the revision of the guideline "Excipients in the label and package leaflet of medicinal products f

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Managing the delicate balance between Purchasing Strategy and Quality Requirements

ABSTRACT: he current political environment, social climate, and economic challenges are creating enormous pricing pressures on the finished drug products marketed by the pharmaceutical industry regardless of branded formulation or a generic product.  These extraordinary pricing pressures are applying greater pressure on the profitability of finished drug products.  The need to maintain the profitability of the finished drug product is in turn driving the purchasing or sourcing strategy for lower cost active pharmaceutical ingredients (APIs) and excipients.  The drive for lower cost raw materials is creating the need to maintain a delicate balance between the Purchasing Strategy and the Quality Requirements during the supplier selection process.  The maintenance of the balance between the Purchasing Strategy and the Quality Requirements requires the use of quality risk management tools and a holistic approach to supplier qualification.

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Excipient Learning Lab by IPEC-AMERICAS

IPEC-Americas Excipient Learning Lab; THE Authority and Resource for Education and Training in Pharmaceutical Excipients.

 

Below are different types of education and training being offered:

 

Public Workshops

In person Excipient GMP training held in major US cities!

 

On Site Training Workshops

Experienced and knowledgeable trainers will come to your facility (or designated location) at a time and date to suit your schedule. Training topics include Excipient GMP or other topics critical to your business!

 

eLearning 

Attendees may register and pay online for self-paced courses, view the course, complete learning evaluations, and receive a certificate of completion once they have successfully finished the course and evaluations.

 

Webinars

IPEC-Americas offers web based training modules on topics critical to manufacturers and users of pharmaceutical excipients/ingredients. Sessions are facilitated by industry professionals and include Q&A time, as well as access to the presentations upon course completion.

 

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Silica from Rice as New Drug Delivery Systems

Abstract

The pharmaceutical industry has seen an increased need of carriers or excipients design that allows the controlled release of a drug in the human body. The main role of an excipient is to carry the drug for its administration under therapeutic index. Among the new generation of excipients, the ordered mesoporous silica (MS) presents several advantages, such as excellent biocompatibility, good adsorption capacity, and precise control in the drug delivery. However, the high cost of synthesis of mesoporous silica restricts its use to industrial applications; therefore, a low-cost procedure is necessary for widespread use. Biogenic silica from rice husk (SiO2-rice) could be a new choice as a drug delivery system. This silica is obtained from an acid leaching of rice husk followed by calcinations processes at low temperatures; these conditions produce silica with good adsorption properties, similar to those of MS. In consequence, the excipient behavior of SiO2-rice was assessed using folic acid as the model drug, displaying an 18.5% of absorption in the SiO2-rice pores, while MS absorbed around 19%. The drug release profiles were similar for both the silicas, suggesting that SiO2-rice could be a low-cost, similar yield excipient for drugs similar to folic acid.

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APV/IPEC Europe Excipient Conference 2017

19.09. - 20.09.2017 | Berlin, Deutschland

An update on regulatory and application developments

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9th Conference of the European Paediatric Formulation Initiative

19 TO 21 SEPTEMBER 2017 IN WARSAW, POLAND

The 9th EuPFI conference series is the ideal forum to learn, grow and to be inspired on the development of age appropriate dosage forms.

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Preparation and In Vitro Evaluation of an Anti-bacterial In Situ Ophthalmic Gel

Abstract:

Background: Conventional dosage forms of neomycin sulphate suffer from different drawbacks like spillage, poor penetration, low bioavailability, etc. In situ ophthalmic gel can overcome these problems by improving bioavailability, decreasing spillage and diminish the need for recurrent application. Thus, the aim of the present work was to prepare and evaluate in situ ophthalmic gel of neomycin sulphate for sustained ocular delivery. 

Method: Two polymers, sodium alginate (0.2-0.7%) and HPMC K4M, were used in different concentrations for the preparation of neomycin sulphate insitu gel. The prepared gel was subjected for rheological study, in vitro gelation, drug release study, antimicrobial study by disk diffusion method and others. 

Result: All formulations were found to be transparent and clear; pH of the formulations was within 6.8 to 6.9; drug content was found within 92-98% in all optimized in situ gelling systems. Viscosity of all formulations decreased as the shear rate increased, which indicated the character of pseudoplastic fluid. Optimized formulations F6 (0.5% Sodium alginate and HPMC K4M 1.5%), F7 (0.3% Sodium alginate and HPMC K4M 1.7%) and F8 (0.4% sodium alginate and HPMC K4M 2%) were liquid before instillation to the eye and underwent rapid gelation upon instillation to the eye. In vitro release through diffusion cell using cellophane membrane for 8 hours revealed sustained release of the drug from sodium alginate polymeric network over 6 hours. Study of antimicrobial efficacy using Pseudomonas aeruginosa for 24 hours showed all formulations to have effective antimicrobial action. Stability study for 6 months had revealed no changes in visual appearance, clarity, pH and % drug content. 

Conclusion: Hence, from the above results we can conclude that in situ ophthalmic gels of neomycin sulphate can be a good option for the treatment of various bacterial eye infections.

 

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Birch Bark Dry Extract by Supercritical Fluid Technology: Extract Characterisation and Use for Stabilisation of Semisolid Systems

Abstract: Triterpene compounds like betulin, betulinic acid, erythrodiol, oleanolic acid and lupeol are known for many pharmacological effects. All these substances are found in the outer bark of birch. Apart from its pharmacological effects, birch bark extract can be used to stabilise semisolid systems. Normally, birch bark extract is produced for this purpose by extraction with organic solvents. Employing supercritical fluid technology, our aim was to develop a birch bark dry extract suitable for stabilisation of lipophilic gels with improved properties while avoiding the use of toxic solvents. With supercritical carbon dioxide, three different particle formation methods from supercritical solutions have been tested. First, particle deposition was performed from a supercritical solution in an expansion chamber. Second, the Rapid Expansion of Supercritical Solutions (RESS) method was used for particle generation. Third, a modified RESS-procedure, forming the particles directly into the thereby gelated liquid, was developed. All three methods gave yields from 1% to 5.8%, depending on the techniques employed. The triterpene composition of the three extracts was comparable: all three gave more stable oleogels compared to the use of an extract obtained by organic solvent extraction. Characterizing the rheological behaviour of these gels, a faster gelling effect was seen together with a lower concentration of the extract required for the gel formation with the supercritical fluid (SCF)-extracts. This confirms the superiority of the supercritical fluid produced extracts with regard to the oleogel forming properties.

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Formulation and characterization of mucoadhesive controlled release matrix tablets of captopril

Abstract

The purpose of this study is to characterize controlled release matrix tablets of captopril and to find out the physicochemical properties that have an effect on the mucoadhesion process. The hydrophilic matrix tablets contain captopril, microcrystalline cellulose, barium sulfate, ascorbic acid, ethylcellulose N100, hydroxypropylmethylcellulose K15M, talc, magnesium stearate and colloidal silicon dioxide. The physicochemical properties of the formulations have been characterized using confocal microscopy, contact angle, and scanning electron microscopy. The potential mucoadhesion capabilities of the formulations were assessed measuring the surface free energy, the polar and dispersive forces, the spreading coefficients, the surface roughness, and the network structure of the hydrophilic matrix tablets. The results show that when the concentration of HPMC K15M increases, the spreading coefficients of polymer over mucus and mucus over polymer are more positive, thus increasing the contact between the matrix tablets with the mucus layer. The formulation that contains 15% of HPMC K15M is the formulation that presents a greater swelling capacity, a greater increase in surface roughness, and larger pores within the matrix. This formulation has a higher chain mobility and more free macromolecular chains able to diffuse in the mucus layer. Therefore, this formulation has the greatest potential mucoadhesion capability.

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Interdependence of Dosage Form Microstructure and Performance

Our understanding of quality in pharmaceutical production has evolved significantly over the past decade. The quality-by-design initiative has proved to be a catalyst for those working in the pharmaceutical science community to reconsider established quality testing protocols and focus research on the effect of processing steps on the quality of dosage forms. With clear progress being made in the implementation of continuous processing into industrial practice there has also been a realisation that pharmaceutical engineering and materials sciences need to be better integrated into existing practice. Traditionally, the pharmaceutical development process, the regulatory process and the testing requirements outlined in the pharmacopeias place a strong emphasis on chemical purity and drug content as well as the safety and efficacy of the medicines. It is this context that has dominated the perception of quality in our community and with which we are all familiar. However, it has become increasingly clear that in order to achieve stable manufacturing processes that result in consistent product quality it is now critical to understand the physical characteristics of drug products in far greater detail than is currently the status quo. The microstructure, that is the physical structure at microscopic scale, determines a significant range of critical quality attributes of a dosage form, given their nature as complex multi-particulate mixtures of drug and excipients.

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Establishing a Formalized Risk Assessment for Excipients

by: Frithjof Holtz, Merck KGaA, Darmstadt, Germany | Dec 06, 2016

 

Excipients serve a critical role in the production of final dosage forms for drug products and biologics. They facilitate the manufacturing process (e.g., anticaking agents) and protect, support, and enhance stability. They may also improve bioavailability. In addition, excipients help maintain the safety, or function, of the product during storage and use.

 

No longer characterized as inert accompaniments to an active pharmaceutical ingredient (API), excipients are the target of an intensified push for more stringent quality management, placing new requirements on both suppliers and users. Regulating excipient quality, however, is no small task. The global market is expected to exceed $5 billion by 2020—with a growth rate of 6.0% from 2014 to 2020 (1). Thousands of different excipients are available, and only a small percentage of them are manufactured solely for pharmaceutical use.

 

For many years, there have been clearly defined GMP requirements for APIs, including EU GMP Part II, 21 CFR Part 11 and ICH Q7: Good Manufacturing Practice for Active Pharmaceutical Ingredients. But, until recently, well-defined and stringent GMP requirements for excipients did not exist.

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SUDEEP PHARMA’S INDIAN SITE RECEIVES EXCiPACT GMP CERTIFICATION AS PHARMACEUTICAL EXCIPIENT SUPPLIERS

Brussels, 21 March 2017 - News Release EXCiPACT

 

EXCiPACT asbl is delighted to announce that the Sudeep Pharma Private Ltd’s Vadodara site in India has recently been awarded an EXCiPACT GMP Certificate from SGS, one of EXCIPACT’s internationally-recognised Certification Bodies.

 

The Certificate demonstrates that the Sudeep Pharma Pvt. Ltd. site in Vadodara, Gujarat, India, manufactures pharmaceutical excipients according to the EXCiPACT Good Manufacturing Practice (GMP) Certification Standard. Its scope covers manufacture of different grades of Di basic calcium phosphate, Tri basic calcium phosphate and calcium carbonate for use as pharmaceutical excipients. For full details of all sites that have been EXCiPACT certified to date in 14 Countries (Canada, China, Belgium, France, Germany, The Netherlands, India, Israel, Saudi Arabia, Singapore, Spain, Switzerland, UK and USA), see http://www.excipact.org/certification/certificates/

 

Both SGS and their auditors had to undergo a rigorous assessment process in order to be EXCiPACT Registered. This required the successful completion of the EXCiPACT Training Programme and post-course examination followed by an independently witnessed audit to verify that their competency was to the required standard. SGS also had to have their auditor’s report verified by an independent certification board prior to issuing the certificate.

EU and U.S. pharmaceutical regulations require drug manufacturers to conduct either their own or commission 3rd party physical audits of all their starting material suppliers to demonstrate GMP and/or GDP compliance thus increasing the audit burden. Using GMP and GDP standards designed for excipients, the independent, high quality 3rd Party EXCiPACT Certification Scheme is already helping excipient users and suppliers to reduce their audit burden, save costs and assure quality.

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OCULAR DRUG DELIVERY – STATE-OF-THE-ART AND NEW CONCEPTS - Featured Article in APV Drug Delivery Focus Group Newsletter – 1/2016

By Lutz Franzen and Florian Unger; Formulation Development, Bayer Pharma AG

 

1. General Overview

On 20th and 21st of June 2016 the International Association for Pharmaceutical Technology (APV) hosted a “high-toned seminar” on ocular drug delivery. At the venue in Berlin an audience from academic and industrial research listened to a comprehensive mix of overview talks and case studies. In the following article we give a brief introduction to the topic of ocular drug delivery and summarize the key findings presented at the seminar.

Arto Urrti from Helsinki University opened with an introductory talk on “Ocular anatomy, physiology, pharmacokinetics & pK modeling“. Pascal Furrer from the University of Geneva followed with a comprehensive overview on ocular dosage forms and the accompanying regulatory requirements.

From a drug delivery perspective the eye can be separated in two parts, the anterior and the posterior segment. The anterior segment includes the cornea, aqueous humor, iris, lens and the conjunctival tissue. The posterior segment is comprised of the vitreous humor surrounded by the choroid, the retina including the macular and adjoining vasculature. In order to account for the anatomical differences a distinction between treatments of diseases in the anterior and pos- terior segment has to be made.

Featured Article in APV Drug Delivery Focus Group Newsletter – 1/2016 | December

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The 5th international Symposium on "Phospholipids in Pharmaceutical Research"

September 18/19, 2017 in Heidelberg, Germany

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Continuous Manufacturing & Excipients CMAs @ Highlights of IPEC Europe Forum 2017

 

Highlights of IPEC Europe Forum 2017

IPEC Europe's annual Excipient Forum took place on 2 February in Monte Carlo, providing the usual high-quality insights into the commercial, regulatory and scientific issues affecting both suppliers and users of pharmaceutical excipients. Marking the occasion of its 25th Anniversary, the programme allowed for reflection on past accomplishments and how this may direct future efforts.  

Susanne Keitel, director of the European Directorate for the Quality of Medicines and Healthcare (EDQM), updated delegates on a diverse range of topics, including ongoing efforts to reform the Pharmacopoeial Discussion Group (PDG) procedure which despite improvements in recent years is still slow and not fully understood.

Changes under consideration include a reduction in the number of steps within the PDG procedure, involving more experts, more often and considering bilateral rather than trilateral harmonisation efforts where there are ‘roadblocks’. Participation with interested parties could also be improved, for example by contributing methods, specifications and batch data earlier in the harmonisation process, taking part in collaborative studies and providing comments at the public enquiry stage.

Tackling the evolving regulatory requirements for excipients in China, IPEC China chair and manager of Colorcon’s regulatory operations in China  Colin Li, explained the changes introduced since the China Food and Drug Administration (CFDA) updated its excipients regulation in August 2016, and published detailed dossier requirements the following November. The new rules state that both domestic and imported excipients will be handled by the Centre of Drug Evaluation (CDE) under the same approval system, whereas previously they were reviewed separately. It is imperative that excipient considerations are included in the drug development process for new products to avoid any possible approval delays.  

He went on to say that guidance on change management for excipients has not yet been published. Possible upcoming developments to look out for include drug master files, the growing importance of the Chinese Pharmacopoeia (ChP) in the regulation of excipients and the possibility that imported drugs – currently exempted from these excipient registration rules - will in time fall under the same requirements as domestically-produced medicines. Excipients manufactured outside of China could be included in inspection programmes, based on risk.

Continuous manufacturing of pharmaceuticals has received a lot of attention in recent years. One of the challenges often cited in switching from batch production is traceability, which can be used to find the root cause of quality issues and facilitate the withdrawal or recall of products. Katia Jambart, head of global quality management system at Roquette, described a method for handling traceability and batch records in continuous processing, noting that it relies on three pillars – documentation, identification and testing.

Companies should carefully document the traceability process, identify products at each step using a unique batch number and material name, and carry out upstream and downstream testing in accordance with a risk analysis. The result is an 'approximate' traceability covering the whole manufacturing and supply chain, she said.

Staying on the theme of continuous manufacturing, Chris Vervaet, head of the Laboratory of Pharmaceutical Technology in the Faculty of Pharmaceutical Sciences at Ghent University in Belgium, gave a presentation on the critical material attributes (CMA) for excipients deployed in continuous processing.

Drawing from case studies involving microcrystalline cellulose (MCC) and hypromellose (HPMC), he presented studies exploring whether the impact of CMAs during continuous manufacturing is similar to batch processing, and whether specific CMAs are more critical during continuous manufacturing compared to batch processing. He concluded that CMAs not relevant during batch processing can be vital during continuous processing, while CMAs can have different impact during continuous manufacturing.

Eckart Kraemer – who chairs IPEC Europe's GDP committee – introduced delegates to the changes incorporated into the soon-to-be-published 2017 IPEC GDP guide for Pharmaceutical Excipients, which will replace the 2006 edition. The revised version offers practical guidance and examples, targeting excipients to complement the World Health Organization (WHO) Good Trade and Distribution practice (GTDP) guide for Starting Materials.

Among the changes and additions in the GTDP guide that need to be taken into account were the incorporation of a risk-management approach to GDP, a greater emphasis on supplier management to ensure authenticity and traceability of the supply chain, and elements designed to ensure the independence of the quality unit. It also advises greater use of preventive actions, including verification of the effectiveness of the distribution system.

Continuing in the same vein, Astrid Stockrahm-Uhling of DFE Pharma, who led the taskforce for the revision of IPEC's Quality Agreement guide, gave a review of the new version which is currently at the final draft stage. The guide covers quality agreements between excipient suppliers, distributors and customers and includes a template with ‘how to’ notes, to help reduce the time needed to draw up such agreements.

New topics added to the 2017 templates cover tamper-evidence features, reworking and reprocessing, and returned excipients, and there are new sections for the customer on ensuring the excipient is appropriate for its intended use and quality control testing of incoming materials. Where an intermediate party may be involved in excipient supply, the use of a Manufacturer’s Quality Statement’ is proposed as an alternative to three-way agreements.   

Rounding off the trio of new guide presentations, Kevin McGlue of Colorcon gave an update on behalf of the GMP guide revision taskforce, which has been working on an update to the 2006 IPEC-Pharmaceutical Quality Group GMP guide edition since mid-2015. The revised version has so far been aligned to the EXCiPACT certification standard and brings in newer concepts such as risk assessment and, having been approved by the IPEC Federation, will soon be published as an IPEC Federation-PQG document.

The work will not stop there, however, as the plan is to further revise it to fully align with ISO 9001:2015 and expand it to include more 'how to' guidance on GMP implementation. The guide sits alongside EXCiPACT and the NSF/IPEC/ANSI 363-2014 and is designed to help producers who are just starting with GMP or as an alternative to certification.

Kicking off the afternoon session, Åsa Pettersson - process engineer expert at AstraZeneca (AZ) – tackled the topic of excipient qualification, giving the pharmaceutical manufacturer's viewpoint when it comes to evaluating new excipients as well as handling changes to the supply of or problems surfacing with established materials.

Pettersson described how AZ handles the excipient life cycle from the screening, pre-project and project stages through to 'business as usual' supply. Once again risk management is the watchword, she noted, along with reliable two-way communication. Uniform excipient quality is critical to the manufacturability and quality of the finished product, and physical characteristics must be taken into account, not only the specification.

Peter Brun of HWI Development took on the topic of modern methods for excipient characterisation/distribution in solid dosage forms, discussing how new technologies such as X-ray micro tomography (XMT), scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM-EDX) and Raman spectroscopy can be valuable tools to understand product properties and tackle quality issues.

Such methods provide "nearly forensic precision" and can provide full understanding of internal structures and defects in most drug dosage forms. It is also possible to fulfil Quality-by-Design (QbD) requirements using these techniques in combination with drug development, variation and optimization programmes.

Data integrity panel

The afternoon rounded off with a panel discussion on the hot topic of data integrity, which is already a major compliance issue for active pharmaceutical ingredients (APIs) and is increasingly in scope for excipients even if the regulatory landscape does not specifically apply to them.

Setting the scene, Tracy Moore, senior GMDP inspector at the UK Medicines and Healthcare products Regulatory Agency (MHRA), told delegates that data integrity is defined as the extent to which all data are complete, consistent and accurate throughout the data lifecycle. Regulators have has been paying more attention to this since 2013 and it is anticipated that changes will come in the inspection approach taken by authorities.

"International inspection findings have identified data integrity as a priority area of focus," she said, pointing to cases in which certificates of analysis (CoA) and GMP certificates have been wilfully falsified, along with other examples of 'tidying' of data by materials suppliers. Companies should design systems and a culture that reduce the chances of any data integrity failures, particularly as there is a migration from paper to electronic records, while regulators and industry must "remain vigilant".

Anne-Catherine Bildstein of Novartis picked up the baton to provide the perspective of the excipient user, acknowledging that it can be difficult for companies to get data integrity right because of performance and business pressure, lack of awareness or capability and inadequate processes and technology.

Data integrity is still not fully integrated into the pharma industry culture, she said, but this can be remedied by raising awareness with communication, training and sharing of information, and making sure technical aspects such as user logins and audit trails are enabled and monitored.

Iain Moore of Croda delivered the point-of-view of the excipient supplier, noting that there should be no fundamental gaps in data integrity principles if producers are following the IPEC-PQG GMP guide. The question is whether this has been applied to data, beyond electronic and paper records, and it will be good practice to do a check on the activities listed in regulatory guidance documents that have been published by the FDA, MHRA and EMA.

A gap analysis could be conducted with questions such as: are records reviewed for completeness; are forms reconciled; and are audit record retention practices audited?, he suggested. It may be an opportunity to check fundamental IT security measures, for example whether logins and passwords are shared, whether records can be edited or deleted, and if leaving workers are systematically removed from the system.

More details of a survey which was conducted to provide some perspectives on data integrity in the excipient community are included in this edition of Excipients Insights.  

Please contact the IPEC Europe Secretariat for any questions related to the IPEC Europe Forum 2017.

 

Link: Excipients Inside January / February 2017

 

Extended release of flurbiprofen from tromethamine-buffered HPMC hydrophilic matrix tablets

Abstract

The pH-dependent solubility of a drug can lead to pH-dependent drug release from hydrophilic matrix tablets. Adding buffer salts to the formulation to attempt to mitigate this can impair matrix hydration and negatively impact drug release. An evaluation of the buffering of hydrophilic matrix tablets containing a pH-dependent solubility weak acid drug (flurbiprofen), identified as possessing a deleterious effect on hydroxypropyl methylcellulose (HPMC) solubility, swelling and gelation, with respect to drug dissolution and the characteristics of the hydrophilic matrix gel layer in the presence of tromethamine as a buffer was undertaken. The inclusion of tromethamine as an alkalizing agent afforded pH-independent flurbiprofen release from matrices based on both HPMC 2910 (E series) and 2208 (K series), while concomitantly decreasing the apparent critical effect on dissolution mediated by this drug with respect to the early pseudo-gel layer formation and functionality. Drug release profiles were unaffected by matrix pH-changes resulting from loss of tromethamine over time, suggesting that HPMC inhibited precipitation of drug from supersaturated solution in the hydrated matrix. We propose that facilitation of diffusion-based release of potentially deleterious drugs in hydrophilic matrices may be achieved through judicious selection of a buffering species.

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Roquette Announces Commitment to Provide New Product Offerings

New product offerings are low endotoxin, multi-compendial-grade materials for cell culture and biologic drug formulations. These products extend Roquette's commitment to helping customers save and sustain patients’ lives.

 

"As a long-time leader in excipients and active ingredients for the pharmaceutical market, Roquette is proud to be part of this major therapeutic progress and is excited to introduce several new products in the US, Europe, and Asia," said Paul Smaltz, VP of Global Business Unit Pharma.

 

"We have three new brands coming to the market under the names LYCADEX BioPharma dextrose, PEARLITOL BioPharma mannitol, and NEOSORB BioPharma sorbitol with a plan to continue adding to the portfolio," added Kelsey Achenbach, Pharma Marketing Director. "Customers now have an alternative option with a partner who is an established manufacturer and has sole custody of the supply chain when it comes to materials for biopharmaceuticals."

 

This investment reaffirms the company's strategic initiatives to develop specialties for Pharma, Food, Nutrition, and Health markets to accelerate global growth. The BioPharma market launch addresses the growing customer demand for biologic drugs worldwide. These protein-based drugs can be game-changing by having the ability to put rheumatoid arthritis into remission and transform many cancers into treatable conditions.

 

A family owned Group serving customers globally, Roquette is a leader in specialty food ingredients and pharmaceutical excipients. The products and solutions developed by the Group deliver proven technological, nutritional, and health benefits precisely tailored to the pharma, nutrition, food, and selected industry markets. Roquette's offer is produced from plant-based raw materials such as corn, wheat, potatoes, and peas. Since its foundation over 80 years ago, the Group's growth has been based on innovation, a passion for the job, and a commitment to achieve. Roquette operates in over 100 countries, has a turnover of around 3.3 billion euros, and currently employs more than 8,000 people worldwide. For more information, visit http://www.roquette.com.

 

See more at: http://drug-dev.com/Main/Current-News/1853.aspx#sthash.38JkpZcq.dpuf

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Additives and "Impurities" in Excipients - IPEC Webinar

Wednesday, June 14, 2017 - 11:00am to 1:00pm

This webinar will discuss additives and “impurities” as they relate to excipients, including concomitant components, why they’re important to excipient function, and regulatory implications of these various entities (e.g., USP General Chapters).

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ROLE OF EXCIPIENTS IN DEVELOPMENT OF TOPICAL DOSAGE FORMS

Abstract

Topical route is the largest and easily accessible administration site for the different therapeutic entities. Although, physicochemical properties of drugs and biological barriers are limiting factors for getting therapeutic outcomes. Several approaches including excipients have been utilized to overcome drawbacks associated with this route.  This review gives an overview of different excipient on the basis of their application in topical delivery of drugs.

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Testing PAT under realistic conditions

Determining the drying endpoint in fluidized bed processes

Whatever the process, whether conti or batch: Process Analytical Technology (PAT) and parametric release are currently the hottest topics in pharmaceutical technology. One example of PAT is determining the drying endpoint in fluidized bed processes. The installation of online moisture sensors makes a whole lot of sense.

Fluid Bed Systems

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Pharmaceutical Lyophilisation Summit

Berlin - 27 - 28 April, 2017

This premier event provides the appropriate platform to discuss and network with peers involved in pharmaceutical manufacturing, R&D, quality control, engineering, and container development.

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20th Microencapsulation Industrial Convention

Nantes, France - April 10-13, 2017

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Characterization of orally disintegrating films: A feasibility study using an electronic taste sensor and a flow-through cell

Abstract

In the early development stage of orally disintegrating films (ODFs), suitable evaluation methods must be used. The aim of this study was to demonstrate the feasibility of using an electronic taste sensor and a flow-through cell for ODFs. A pullulan film loaded with donepezil hydrochloride (DH) was designed, as a model ODF. The film was prepared using the solution/solvent casting method. First, the dissolution profiles were compared by using a paddle method (PD) and a flow-through cell method (FT) under three flow rates. Dissolution tests using both methods were carried out successfully. Secondly, the bitterness of ODFs was determined by a new system combining a flow-through cell apparatus and an electronic taste sensor apparatus. The results indicated that the FT method can collect eluate for the bitterness test. They also suggested that these methods are useful for evaluating ODFs. The sensor output was strongly correlated with the dissolution behavior at the initial stage of administration. This new system with a flow-through cell and an electronic taste sensor could be used to evaluate the palatability of ODFs and to improve film formulation.

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Carobomer Based Controlled Release Designs of Atorvastatin Calcium Tablets Evaluated Using Quality by Design (QbD) Approach

ABSTRACT

The study carried out here was focused on developing conventional monolithic controlled release matrix tablet of Atorvastatin calcium using carbomer as release controlling polymer. This system ensures the drug release at the alkaline pH region where the drug has got maximum solubility. Further the study was concentrated on comparing the impact of gelling agent polyvinyl pyrrolidone on drug release. Quality by design tools were considered during formulation development and the polymer concentrations were optimized adopting the statistical tool, design of experiments (DoE). The optimized formulation of present study exhibited desired controlled drug release characteristics in the alkaline pH conditions and at acidic environment the drug dissolution was minimal as intended.

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Physicochemical characterization and compatibility study of roflumilast with various pharmaceutical excipients

Abstract

Roflumilast (RFL), a newly approved and highly selective phosphodiesterase 4 inhibitor for the treatment of severe chronic obstructive pulmonary disease, associated with chronic bronchitis and a history of numerous exacerbations. The main objective of this work was to evaluate the simultaneous (TG/DSC) thermoanalytical characterization and compatibility of roflumilast with the widely used excipients for solid dosage form employing differential scanning calorimetry (DSC), thermogravimetric analysis (TG), optical microscopy, isothermal stress testing (IST) by HPLC and liquid chromatography–mass spectrometer techniques with Fourier transform infrared spectroscopy (FT-IR) as a complimentary technique to contribute in the interpretation of results. The selected excipients were pregelatinized starch (PS), magnesium stearate, croscarmellose sodium (CCS), microcrystalline cellulose (MCC) and sodium starch glycolate (SSG). The DSC curve showed a sharp endothermic melting peak at 160.43 °C for roflumilast. On the basis of the DSC results, some interactions were found with RFL–CCS, RFL–MCC, RFL–SSG and RFL–PS. However, during IST studies less than 2% change in roflumilast content was observed in all stressed physical mixtures except RFL–SSG (<14%) which showed incompatibility with roflumilast. These results would be suitable for formulation development of the film-coated tablets of roflumilast.

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Evaluation of Analytical and Sampling Errors in the Prediction of the Active Pharmaceutical Ingredient Concentration in Blends From a Continuous Manufacturing P

Abstract

Purpose

A near-infrared (NIR) spectroscopic method was developed for real time analysis of the active pharmaceutical ingredient (API) in blends from a continuous manufacturing process. The sampling and analytical errors of these determinations were estimated through variographic analysis.

Methods

Thirty-three calibration blends were prepared in laboratory scale equipment with a concentration range spanning from 70 to 130% of API target concentration. The NIR calibration model was validated using three independent validation sets (prepared in laboratory and pilot plant facilities and in the CM equipment). Real-time NIR spectra were obtained with an interface where three NIR spectrometers monitored the CM process. A variographic study was performed with the NIR predictions of drug concentration in blends.

Results

A total of 1800 NIR spectra were obtained throughout a CM run that lasted 2.5 h. Two NIR spectrometers (M1 and M2) monitored the CM run while located in positions b-1 and b-3 of the sensing interface. These two positions yielded very similar results. The average NIR predictions for blends were 101.67% LC for the first run using spectrometer M1 and 103.60% LC with M2. The second run provided an average NIR prediction of 101.19% LC with M1 and 103.16% LC with M2. The average drug concentration in tablets was 100.63% LC for the first run and 100.42% LC for the second run. Variograms showed a low sill and a flat, stable variogram demonstrating good mixing of the blend.

Conclusion

The CM process provided tablets with excellent content uniformity. The sampling and analytical errors and the true process variation were easily discerned through variographic analysis.

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Supercritical antisolvent co-precipitation of rifampicin and ethyl cellulose

Abstract

Rifampicin-loaded submicron-sized particles were prepared through supercritical anti-solvent process using ethyl cellulose as polymeric encapsulating excipient. Ethyl acetate and a mixture of ethyl acetate/dimethyl sulfoxide (70/30 and 85/15) were used as solvents for both drug and polymeric excipient. When ethyl acetate was used, rifampicin was crystallized separately without being embedded within the ethyl cellulose matrix while by using the ethyl acetate/dimethyl sulfoxide mixture, reduced crystallinity of the active ingredient was observed and a simultaneous precipitation of ethyl cellulose and drug was achieved. The effect of solvent/CO2 molar ratio and polymer/drug mass ratio on the co-precipitates morphology and drug loading was investigated. Using the solvent mixture, co-precipitates with particle sizes ranging between 190 and 230 nm were obtained with drug loading and drug precipitation yield from respectively 8.5 to 38.5 and 42.4 to 77.2% when decreasing the ethyl cellulose/rifampicin ratio. Results show that the solvent nature and the initial drug concentrations affect morphology and drug precipitation yield of the formulations. In vitro dissolution studies revealed that the release profile of rifampicin was sustained when co-precipitation was carried out with the solvent mixture. It was demonstrated that the drug to polymer ratio influenced amorphous content of the SAS co-precipitates. Differential scanning calorimetry thermograms and infrared spectra revealed that there is neither interaction between rifampicin and the polymer nor degradation of rifampicin during co-precipitation. In addition, stability stress tests on SAS co-precipitates were carried out at 75% relative humidity and room temperature in order to evaluate their physical stability. SAS co-precipitates were X-ray amorphous and remained stable after 6 months of storage. The SAS co-precipitation process using a mixture of ethyl acetate/dimethyl sulfoxide demonstrates that this strategy can be successful for controlling rifampicin delivery.

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Cyclosporine A delivery to the eye: a comprehensive review of academic and industrial efforts

Abstract

Local ocular delivery of cyclosporine A (CsA) is the preferred method for CsA delivery as a treatment for ocular inflammatory diseases such as uveitis, corneal healing, vernal keratoconjunctivitis and dry eye disease. However, due to the large molecular weight and hydrophobic nature of CsA and the natural protective mechanisms of the eye, achieving therapeutic levels of CsA in ocular tissues can be difficult. This review gives a comprehensive overview of the current products available to clinicians as well as emerging drug delivery solutions that have been developed at both the academic and industry levels.

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Orodispersible Films: Towards Drug Delivery in Special Populations

Abstract

Orodispersible films (ODF) hold promise as a novel delivery method, with the potential to deliver tailored therapies to different patient populations. Together with the current trends and potential therapeutic areas such technology can address, some of the unmet needs in terms of quality aspects and manufacturing of conventional and novel (printed) ODF are discussed. Overall, this article aims to stimulate further research to fill the current knowledge gap between manufacturing and administration requirements of ODF targeting specific patient subpopulations such as geriatrics.

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Surface area, volume and shape descriptors as a novel tool for polymer lead design and discovery

Abstract

In recent years, the demand and interest for functionalized polymers have increased for drug delivery purposes. Because of the increased interest, methods that can be used to predict physical and chemical properties of polymers prior to synthesis would be of high value for the design and development of novel polymer structures. Through use of molecular descriptors and Principal Component Analysis, this study explores the possibilities of using in silico methods for polymer design and characterization for property prediction. The results presented in this paper suggest that it is possible to produce a model, which can successfully distinguish between a set of both structurally similar and different polymers based on their surface properties.

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A systematic study of molecular interactions of anionic drugs with a dimethylaminoethyl methacrylate copolymer regarding solubility enhancement.

Abstract

The methacrylate-copolymer Eudragit® EPO (EPO) has raised interest in solubility enhancement of anionic drugs. Effects on aqueous drug solubility at rather low polymer concentrations are barely known despite of their importance upon dissolution and dilution of oral dosage forms. We provide evidence for substantial enhancement (factor 4-230) of aqueous solubility of poorly water-soluble anionic drugs induced by low (0.1-5% (w/w)) concentration of EPO for a panel of seven acidic crystalline drugs. Diffusion data (determined by 1H nuclear magnetic resonance spectroscopy) indicate that the solubility increasing effect monitored by quantitative ultra-pressure liquid chromatography was caused primarily by molecular API polymer interactions in the bulk liquid phase. Residual solid API remained unaltered as tested by X-ray powder diffraction. The solubility enhancement (SE) revealed a significant rank correlation (rSpearman= -0.83) with rDiffAPI, where SE and rDiffAPI are defined ratios of solubility and diffusion coefficient in the presence and absence of EPO. SE decreased in the order of indomethacin, mefenamic acid, warfarin, piroxicam, furosemide, bezafibrate, and tolbutamide. The solubilizing effect was attributed to both ionic and hydrophobic interactions between drugs and EPO. The excellent solubilizing properties of EPO are highly promising for pharmaceutical development and the dataset provides first steps towards an understanding of drug-excipient interaction mechanisms.

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Bridging Justifications: Supporting the Safety of Excipients in Generic Drug Products (Presentation)

Outline

• Excipient safety review in generic drug applications

• Bridging justifications for excipients in generic drugs – What is their utility?

   – What are important factors to consider?

• Case Studies

  – Excipient grade, dose, duration, route of administration, patient population

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Colon-targeted delivery of solubilized bisacodyl by doubly enteric-coated multiple-unit tablet

Abstract

A doubly enteric-coated multiple-unit tablet (DET) of bisacodyl (BD) was formulated to selectively deliver the stimulant laxative to the large intestine. Solubilized BD in surfactants was adsorbed into the porous carrier and primarily coated with different combinations of pH-sensitive polymers (Eudragit S and Eudragit L) and time-dependent release polymer (Eudragit RS). BD-loaded granules were compressed into tablets and coated again with pH-sensitive polymers (Eudragit S:Eudragit L = 1:1). The multiple-unit tablet was optimized with respect to the granular coating compositions (Eudragit S:Eudragit L:Eudragit RS = 5:1:4) and coating level (12.5%), and coating level on the tablet (25%), by evaluating in vitro release profile in continuous dissolution medium. Drug release from the optimized tablet was effectively retarded in the simulated gastric and small intestinal fluids (below 7%), but profound drug liberation was attained in the colonic fluid (over 50%). On the other hand, drug release from the marketed product (Dulcolax®, Boehringer Ingelheim Pharma), a reference drug, in the gastric and small intestinal fluids was reached to 30%, while that in the colonic fluid was only 7%. In an in vivo efficacy study in loperamide-induced constipated rabbits, a remarkable recovery in fecal secretion was observed in the DET-treated group 24 h post-dosing, compared to vehicle-treated (p < 0.05) and the marketed product-treated groups (p < 0.05). Moreover, pharmacokinetic evaluation in the constipated rabbits revealed that the DET system significantly lowered the systemic exposure compared with the marketed product (p < 0.05), by hindering drug release in the upper intestine, a preferential absorption site. Therefore, the novel colon-targeted delivery system may be an alternative for boosting pharmacological responses in the colon, while diminishing the intestinal irritation and/or systemic adverse effect of the stimulant laxative.

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Formulation of hydrophobic peptides for skin delivery via coated microneedles

Abstract

Microneedles (MNs) have been investigated as a minimally-invasive delivery technology for a range of active pharmaceutical ingredients (APIs). Various formulations and methods for coating the surface of MNs with therapeutics have been proposed and exemplified, predominantly for hydrophilic drugs and particulates. The development of effective MN delivery formulations for hydrophobic drugs is more challenging with dosing restrictions and the use of organic solvents impacting on both the bioactivity and the kinetics of drug release. In this study we propose a novel formulation that is suitable for MN coating of hydrophobic auto-antigen peptides currently being investigated for antigen specific immunotherapy (ASI) of type 1 diabetes. The formulation, comprising three co-solvents (water, 2-methyl-2-butanol and acetic acid) and polyvinylalcohol 2000 (PVA2000) can dissolve both hydrophilic and hydrophobic peptide auto-antigens at relatively high, and clinically relevant, concentrations (25 mg/ml or 12.5 mg/ml). The drug:excipient ratio is restricted to 10:1 w/w to maximise dose whilst ensuring that the dry-coated payload does not significantly impact on MN skin penetration performance. The coating formulation and process does not adversely affect the biological activity of the peptide. The delivery efficiency of the coated peptide into skin is influenced by a number of parameters. Electropolishing the metal MN surface increases delivery efficiency from 2.0 ± 1.0% to 59.9 ± 6.7%. An increased mass of peptide formulation per needle, from 0.37 μg to 2 μg peptide dose, resulted in a thicker coating and a 20% reduction in the efficiency of skin delivery. Other important performance parameters for coated MNs include the role of excipients in assisting dissolution from the MNs, the intrinsic hydrophobicity of the peptide and the species of skin model used in laboratory studies. This study therefore both exemplifies the potential of a novel formulation for coating hydrophobic and hydrophilic peptides onto MN devices and provides new insight into the factors that influence delivery efficiency from coated MNs. Importantly, the results provide guidance for identifying critical attributes of the formulation, coating process and delivery device, that confer reproducible and effective delivery from coated MNs, and thus contribute to the requirements of the regulators appraising these devices.

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Advances and development in transdermal drug delivery system-A Review

Abstract

It is one of the best pharmaceutical dosage forms for those patients, they cannot take medicaments orally. Transdermal drug delivery system (TDDS) established itself as an integral part of novel drug delivery systems (NDDS). On the application of Transdermal patches, the delivery of the drug across dermis gives the systemic effect. TDDS is costly alternative to conventional formulation. It is also important due to its unique advantage. Controlled absorption, more uniform plasma levels, improved bioavailability, reduced side effects, painless and simple application and flexibility of terminating drug administration by simply removing the patch from the skin are some of the potential advantages of transdermal drug delivery. Development of controlled release transdermal dosage form is a complex process involving extensive efforts. This review article describes the methods of preparation of different types of transdermal patches. In addition, the various methods of evaluation of transdermal dosage form and Advance Development in TDDS have also been reviewed.

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Formulation and PEGylation optimization of the therapeutic PEGylated phenylalanine ammonia lyase for the treatment of phenylketonuria

Abstract

Phenylketonuria (PKU) is a genetic metabolic disease in which the decrease or loss of phenylalanine hydroxylase (PAH) activity results in elevated, neurotoxic levels of phenylalanine (Phe). Due to many obstacles, PAH enzyme replacement therapy is not currently an option. Treatment of PKU with an alternative enzyme, phenylalanine ammonia lyase (PAL), was first proposed in the 1970s. However, issues regarding immunogenicity, enzyme production and mode of delivery needed to be overcome. Through the evaluation of PAL enzymes from multiple species, three potential PAL enzymes from yeast and cyanobacteria were chosen for evaluation of their therapeutic potential. The addition of polyethylene glycol (PEG, MW = 20,000), at a particular ratio to modify the protein surface, attenuated immunogenicity in an animal model of PKU. All three PEGylated PAL candidates showed efficacy in a mouse model of PKU (BTBR Pahenu2) upon subcutaneous injection. However, only PEGylated Anabaena variabilis (Av) PAL-treated mice demonstrated sustained low Phe levels with weekly injection and was the only PAL evaluated that maintained full enzymatic activity upon PEGylation. A PEGylated recombinant double mutant version of AvPAL (Cys503Ser/Cys565Ser), rAvPAL-PEG, was selected for drug development based on its positive pharmacodynamic profile and favorable expression titers. PEGylation was shown to be critical for rAvPAL-PEG efficacy as under PEGylated rAvPAL had a lower pharmacodynamic effect. rAvPAL and rAvPAL-PEG had poor stability at 4°C. L-Phe and trans-cinnamate were identified as activity stabilizing excipients. rAvPAL-PEG is currently in Phase 3 clinical trials to assess efficacy in PKU patients.

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EC Unveils Revised Guideline on Pharmaceutical Excipients

The European Commission on Tuesday opened for public comment a revised guideline concerning the list of excipients, defined as any constituents of a medicinal product other than the active substance and the packaging material, which must be included on the labeling of medicines, as well as the way in which these excipients must be indicated. 

 

The guideline’s revision, which the EC says reflects developments since 2003, includes a list of excipients which should be stated on the label and outlines the information for those which must appear on the package leaflet.

 

See more at: http://www.raps.org/Regulatory-Focus/News/2017/02/28/26976/EC-Unveils-Revised-Guideline-on-Pharmaceutical-Excipients/#sthash.ZxqdezZc.dpuf

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CARBAGAS DOMDIDIER SITE IN SWITZERLAND RECEIVES EXCiPACT GMP CERTIFICATION AS PHARMACEUTICAL EXCIPIENT SUPPLIERS

Brussels, 14 March 2017

EXCiPACT asbl is delighted to announce that the Carbagas Domdidier site has recently been awarded an EXCiPACT Certificate from AJA, one of EXCIPACT’s internationally-recognised Certification Bodies.

 

The Certificate demonstrates that the Carbagas site in Domdidier, Switzerland, manufactures pharmaceutical excipients according to the EXCiPACT Good Manufacturing Practice (GMP) Certification Standard. Its scope covers manufacturing (filling) of pharmaceutical grade gases (nitrogen, oxygen, argon, carbon dioxide) in cylinders and bundles. For full details of all sites that have been EXCiPACT certified to date in 14 Countries (Canada, China, Belgium, France, Germany, The Netherlands, India, Israel, Saudi Arabia, Singapore, Spain, Switzerland, UK and USA), see htttp://www.excipact.org/certification/certificates/

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Insight into a Novel Strategy for the Design of Tablet Formulations Intended for Direct Compression

Abstract

In a recent study, it was demonstrated that improving flow of a model poorly flowing and poorly compactable drug substance, acetaminophen, via dry-coating while using fine excipients may promote direct compression. To validate this novel strategy, particularly for high drug loading formulations, this study investigates the effect of microcrystalline cellulose (MCC) particle size and dry-coating on powder tabletability and flowability. It was determined that blends containing fine-sized MCC (20 μm) resulted in the highest tablet tensile strength and best tabletability since it provides higher inter-particle contact area compared to coarser-sized MCC. While tabletability can be improved by using fine MCC, flowability is poor but can be improved via dry-coating, a process which coats glidants (nano-sized silica) onto particle surfaces. In order to retain the tabletability, which was adversely impacted dues to the presence of glidant in the blend, while simultaneously enhancing flowability via dry-coating, separately blending the drug substance with glidant is shown to be the best method of processing. The combined use of fine excipients and selective dry-coating offers a novel and advantageous formulation strategy in comparison to the conventional use of coarse excipients such as Avicel PH 102 that have been designed and marketed for direct compression.

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Multifractal and mechanical analysis of amorphous solid dispersions

Abstract

The formulation of lipophilic and hydrophobic compounds is a challenge for the pharmaceutical industry and it requires the development of complex formulations. Our first aim was to investigate hot-melt extrudate microstructures by means of multifractal analysis using scanning electron microscopy imaging. Since the microstructure can affect solid dosage form performance such as mechanical properties, a second objective was to study the influence of the type of adsorbent and of the presence of an amorphous compound on extrudate hardness. β-Carotene (BC) was chosen as poorly water-soluble model compound. Formulations containing a polymer, a lipid and two different silica based inorganic carriers were produced by hot-melt extrusion. Based on scanning electron microscopy/energy dispersive X-ray spectroscopy, the obtained images were analyzed using multifractal formalism. The breaking force of the strands was assessed by a three point bending test. Multifractal analysis and three point bending results showed that the nature of interparticle interactions in the inorganic carrier as well as the presence of amorphous BC had an influence on the microstructure and thus on the mechanical performance. The use of multifractal analysis and the study of the mechanical properties were complementary to better characterize and understand complex formulations obtained by hot-melt extrusion.

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Prosopis alba exudate gum as novel excipient for fish oil encapsulation in polyelectrolyte bead system

Abstract

In this work, a bottom-up approach based on the study of polyelectrolyte interactions was performed in order to evaluate the effect of Prosopis alba exudate gum as novel excipient for fish oil encapsulation in composed calcium-alginate-chitosan beads. Emulsion and beads properties such as oil distribution, encapsulation efficiency, yield, microstructure and thermo-oxidative protection were evaluated. Alginate and gum exert a synergistic effect on emulsion stability properties, which conducted to better oil distribution in the beads and higher encapsulation efficiencies (98%) and yield (89%). The positive effect of including the gum as wall material was observed in terms of a higher oil retention capacity of the alginate beads, improved oxidative thermal stability and better microstructural features. Present results are promising and allowed considering P. alba gum as a novel non-conventional polyelectrolyte for improving Ca-alginate beads microstructure and stability with the added benefit of taking advantage of an available resource currently untapped.

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Pharmacokinetics and correlation between in vitro release and in vivo absorption of bio-adhesive pellets of panax notoginseng saponins

Abstract

The present study was designed to prepare and compare bio-adhesive pellets of panax notoginseng saponins (PNS) with hydroxy propyl methyl cellulose (HPMC), chitosan, and chitosan : carbomer, explore the influence of different bio-adhesive materials on pharmacokinetics behaviors of PNSbio-adhesive pellets, and evaluate the correlation between in vivo absorption and in vitro release (IVIVC). In order to predict the in vivo concentration-time profile by the in vitro release data of bio-adhesive pellets, the release experiment was performed using the rotating basket method in pH 6.8 phosphate buffer. The PNS concentrations in rat plasma were analyzed by HPLC-MS-MS method and the relative bioavailability and other pharmacokinetic parameters were estimated using Kinetica4.4 pharmacokinetic software. Numerical deconvolution method was used to evaluate IVIVC. Our results indicated that, compared with ordinary pellets, PNS bio-adhesive pellets showed increased oral bioavailability by 1.45 to 3.20 times, increased Cmax, and extended MRT. What's more, the release behavior of drug in HPMC pellets was shown to follow a Fickian diffusion mechanism, a synergetic function of diffusion and skeleton corrosion. The in vitro release and the in vivo biological activity had a good correlation, demonstrating that the PNS bio-adhesive pellets had a better sustained release. Numerical deconvolution technique showed the advantage in evaluation of IVIVC for self-designed bio-adhesive pellets with HPMC. In conclusion, the in vitro release data of bio-adhesive pellets with HPMC can predict its concentration-time profile in vivo.

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Swelling and mass transport properties of nanocellulose-HPMC composite films

Abstract

Composite films were sprayed from mixtures of water soluble hydroxypropyl methylcellulose (HPMC) and either nanofibrillated cellulose (NFC) or cellulose nanocrystals (CNC). Fiber diameter was similar for both nanocelluloses but fiber length was several μm for NFC and about 200 nm for CNC. Films were characterized for morphology, swelling, mass loss and transport properties. NFC-HPMC films swelled less than CNC-HPMC films; with a HPMC content of 20 wt% NFC-HPMC and CNC-HPMC films presented swelling of 7 and 75 g/g, respectively. The swelling strongly influenced water transport across the films, with slower transport for CNC-based materials compared to NFC-based materials. The properties of NFC-based films were comparable to previous results using microfibrillated cellulose (MFC) with heterogeneous structural content and fiber lengths of ~ 10 μm. The findings have implications for using nanocellulose to modulate material properties in wet-state applications, with effects being in strong contrast when using as a hardening filler in dry materials.

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Stability of pharmaceutical salts in solid oral dosage forms

Using pharmaceutical salts in solid dosage forms can raise stability concerns, especially salt dissociation which can adversely affect the product performance. Therefore, a thorough understanding of the salt instability encountered in solid state formulations is imperative to ensure the product quality. The present article uses the fundamental theory of acid base, ionic equilibrium, relationship of pH and solubility as a starting point to illustrate and interpret the salt formation and salt disproportionation in pharmaceutical systems. The criteria of selecting the optimal salt form and the underlying theory of salt formation and disproportionation are reviewed in detail. Factors influencing salt stability in solid dosage forms are scrutinized and discussed with the case studies. In addition, both commonly used and innovative strategies for preventing salt dissociations in formulation, on storage, and during manufacturing will be suggested herein. This article will provide formulation scientists and manufacturing engineers an insight into the mechanisms of salt disproportionation and salt formation, which can help them avoid and solve the instability issues of pharmaceutical salts in the product design.

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Delivering the Promise of Continuous Secondary Manufacturing

• Drivers for continuous secondary OSD
• Technical barriers for implementation
• TSG case study ( residence time distribution and process
   understanding examples)
• Proposed focus areas for future platform evolution

The pharmaceutical industry is under tremendous pressure to change. For manufacturing and product development, industry is striving to deliver :


• Enhanced product quality, quality assurance and process robustness
• Small flexible manufacturing footprint at low cost and environmental impact
• Minimised development and technical transfer costs and resources.

This has driven a move towards continuous OSD manufacturing. This presentation will review drivers for change, some of the technical barriers to implementation with reference to a TSG case study. It will conclude with a perspective on areas for focus in the future.
Richard Elkes
R&D continuous secondary OSD engineering lead
GSK

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Introduction to VPA (vaporized peracetic acid) sterilization; A new path to innovation and Efficiency

Traditional sterilization methods, such as ethylene oxide (EO), gamma radiation can leave behind dangerous carcinogenic residuals or even damage and degrade a product’s materials or packaging. REVOX has developed a room-temperature sterilization process that uses Vaporized Peracetic Acid (VPA) to gently sterilize all surfaces of a product within its package. This patented technology has excellent penetration capabilities, and leaves behind no residuals. VPA breaks down into relatively harmless, naturally occurring substances: water, oxygen, and carbon dioxide. The safety and easy installation of the REVOX VPA system provides manufacturers the ability to add efficient in-line sterilization to their manufacturing process. VPA has been verified safe and effective for use on over 100 materials, including thermoplastics, adhesives, bio-absorbables, metals, and more, and has been approved as the sterilization method on a FDA 501(k) approved Class II medical device. VPA sterilization makes it possible for manufacturers to safely disinfect products without exposing them to high temperatures, moisture, radiation, or hazardous chemical byproducts. Learn more about VPA, its applications, and how it can work for you.
Mason Schwartz
Inventor of REVOX VPA technology & Director of R&D and Operations
REVOX Sterilization Solutions

 

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TA Associates Announces Investment in Ideal Cures

March 14, 2017 12:00 AM Eastern Daylight Time

BOSTON & MUMBAI, India--()--TA Associates, a leading global growth private equity firm, today announced it has completed an investment in Ideal Cures Private Limited, a supplier of ready-to-use coating products and excipients for tablets and capsules to the pharmaceutical and allied industries. Financial terms of the transaction were not disclosed.

 

Founded in 1999 in India, Ideal Cures’ products are used to provide aesthetic coatings as well as functional coatings for tablets and capsules. Aesthetic sugar or film coatings allow for swallowability and taste masking. They also aid brand recognition, authentication and differentiation. Functional coatings serve a number of purposes ranging from moisture, oxygen and light protection of drugs to controlling drug delivery to a specific part of the gastrointestinal tract. Ideal Cures also produces specialty excipients such as neutral pellets, cooling compounds, taste masking agents, controlled release polymer blends and pharma acrylic polymers. Ideal Cures has three manufacturing plants located in Vasai, Jammu and Khambat; and two state-of-the-art R&D facilities in Mumbai and Vasai. Another plant is under construction in Sikkim.

“We believe that Ideal Cures has a robust business strategy, and over the last few years has emerged as a provider of high quality products and services in the tablet coating space, with a vast and diversified customer base globally,” said Dhiraj Poddar, Country Head of India, TA Associates Advisory Private Limited, who will join the Ideal Cures Board of Directors. “Ideal Cures has worked diligently to innovate solutions that meet the needs of the pharmaceutical and allied industries, building exceptional manufacturing, research and development, and technical services capabilities to rapidly expand their operations. We are thrilled to have the opportunity to partner with Ideal Cures and we look forward to helping their experienced team to drive growth.”

TA Associates believes that the trend is to outsource the production of ready-to-use, fully-formulated coatings, which is being driven most notably by companies seeking innovative solutions that reduce processing time and a company’s carbon foot print such as Ideal Cures provides.

“To be a preferred global supplier of coatings and excipients, we have made it our mission over the course of our more than 15-year history to provide our customers with pioneering research and development, excellent technical support and good manufacturing practices,” said Suresh Pareek, Founder and Managing Director of Ideal Cures. “We are confident that TA Associates’ experience of investing in the healthcare sector will provide the financial and operational expertise to help us expand upon our solutions. We are pleased to welcome TA’s investment and look forward to benefitting from this partnership.”

“Ideal Cures’ business, which is focused on innovation, best-in-class products, state-of-the art facilities and a well-trained and committed professional workforce, continues to evolve,” said Kamlesh Oza, President – Global Business Development at Ideal Cures. “With the advent of TA Associates coming on board, Ideal Cures aims to leverage TA’s networking and other corporate development capabilities to accelerate growth in not only some of the fastest growing regions, like South Asia, but also in well established markets around the world.”

“We believe that the film coating industry is a unique, yet evolving sector that has strong potential for growth globally,” said Naveen A. Wadhera, a Managing Director at TA Associates. “We expect that there are significant opportunities for expansion and are eager to help Ideal Cures further develop and enhance its brand and internal capabilities. We are delighted that Ideal Cures has chosen to partner with TA and look forward to helping them execute on their strategic vision.”

K Law served as legal counsel to Ideal Cures and DSK Legal served as legal counsel to TA Associates. TA Associates Advisory Private Limited provided advisory services on the investment.

About Ideal Cures
Ideal Cures is a leading manufacturer and exporter of pharmaceutical excipients and ready-to-use coating systems for solid oral dosage forms. Through its network of customers and partners spanning across more than 40 countries, the company provides tailor-made solutions and products for the pharmaceutical, nutraceutical, herbal and ayurvedic industries. Ideal Cures has EXCiPACT™ certified cGMP manufacturing plants located in Vasai, Jammu and Khambat and R&D facilities in Mumbai and Vasai. The product portfolio comprises of INSTACOAT® ready-to-use film coating systems, INSTANUTE® coating technology for nutraceuticals and dietary supplements, ECOPOL® range of Pharma Acrylic Polymer’s, ECOCOOL® brand of cooling compounds, ESPHERES® range of sugar, microcrystalline cellulose, silicon dioxide, calcium carbonate and tartaric acid spheres. More information about Ideal Cures can be found at www.idealcures.com.

About TA Associates
TA Associates is one of the largest and most experienced global growth private equity firms. The firm has invested in more than 480 companies around the world and has raised $24 billion in capital. With offices in Boston, Menlo Park, London, Mumbai and Hong Kong, TA Associates leads buyouts and minority recapitalizations of profitable growth companies in the business services, consumer, financial services, healthcare and technology industries. More information about TA Associates can be found at www.ta.com.

 

Contacts

For Ideal Cures:
Ideal Cures
Suresh Pareek, +91 22 42688 711
pareeksuresh@idealcures.com
or
For TA Associates:
TA Associates
Marcia O’Carroll, 617-574-6796
mocarroll@ta.com
or
BackBay Communications
Stephen Fishleigh, +44 203-475-7552
stephen.fishleigh@backbaycommunications.com
or
Zachary Tramonti, 617-391-0797
zachary.tramonti@backbaycommunications.com

 

Mesoporous Silica: A Drug Delivery Platform for Solubility Enhancement

Grace will present a detailed discussion of the mechanisms of silica for solubility enhancement for BCS class II drugs. We will introduce effective methods of particle engineering of compendial silicon dioxide to create stable amorphous dispersions.Specific discussion will include:

  • Case studies demonstrating technology efficacy
  • Practical considerations for scale up and formulation development
  • Benefits of this technology for transfer to clinical trials

Additionally, Grace will demonstrate the value creation of using compendial silicon dioxide for drug delivery.

Fred Monsuur
Global Excipients Commercial Development Manager
Grace

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Using Nanotechnology to Improve Excipients - IPEC Webinar Mar 15, 2017

Nanotechnology, the science of the very small, is rapidly evolving. It enables exciting improvements in many applications, and excipients are no exception! 

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A retrospective and observational analysis of harmful excipients in medicines for hospitalised neonates in Latvia

Background Medicines used in neonates contain different excipients, which may not be safe in this age group.

Objective To analyse the frequency at which hospitalised neonates are exposed to harmful excipients (HEs) and to identify substitution possibilities for medicines containing HEs.

Materials and methods Retrospective, observational study at a university paediatric hospital from 1 September 2015 till 29 February 2016. All hospitalised neonates who received a prescription for medicines containing an HE were included. Neonates were divided into four groups according to gestational age (<28 weeks; 28 to <32 weeks; 32 to <37 weeks and ≥37 weeks). The following excipients were analysed: parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride. Excipients were identified from the Summaries of Product Characteristics.

Results 296 (102(34.5%) preterm) neonates included in the study received 1472 prescriptions for 106 medicines. The most often used formulations were intravenous (48/106; 45.3%) and oral solid formulations (20; 18.9%). The total number of different excipients was 169. In total, 29/106 (27.4%) medicines contained at least one HE. In total 82/102 (80.4%) preterm and 118/194 (60.8%) term neonates received medications with at least one HE. Substitution was possible for 9/29 (31.0%) HE-containing medicines.

Conclusions Use of HEs can be reduced by using HE-free products available on the European market. However, medicine substitution was possible in only a small number of cases. Therefore the main focus should be on information and education of the hospital specialists about HEs used in medicines and their adverse reactions.

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New possibilities using AFFINISOL™ excipients Exploring a platform of tailored polymers for solubility enhancement

AFFINISOL™ polymers are uniquely tailored to address solubilization performance requirements. Several case studies will be presented:

AFFINISOL™ for Spray Dried Dispersions

  • HPMCAS products with a broad range of release properties
    Creating an amorphous dispersion via top spray-granulation
  • AFFINISOL™ HPMC for Hot Melt Extrusion

New cellulosic materials maintaining the crystallization inhibiting properties of traditional HPMC, but can be extruded over a wide temperature range without the use of plasticizers

Next generation of AFFINISOL™

  • Innovative cellulosics and non-cellulosics based excipients addressing solubility challenges

Meinolf Brackhagen

Senior Scientist, Pharma TS&D

Dow Pharma Solutions

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Exploring Canine-Human Differences in Product Performance. Part II: Use of Modeling and Simulation to Explore the Impact of Formulation on Ciprofloxacin In Vivo

Abstract

This study explored the in vivo performance of three oral ciprofloxacin formulations (oral solution, fast, or slow dissolving tablets) in beagle dogs. The in vivo absorption and dissolution behaviors, estimated with in silico mechanistic models, were compared to the results previously published in human volunteers. Six normal healthy male beagle dogs (five to completion) received three oral formulations and an intravenous infusion in a randomized crossover design. Plasma ciprofloxacin concentrations were estimated by tandem mass spectrometry detection. A mechanistic absorption model was used to predict the in vivo dissolution and absorption characteristics of the oral formulations. Canine ciprofloxacin absorption was constrained to the duodenum/jejunum. This absorption window was far narrower than that seen in humans. Furthermore, while substantial within-individual variability in drug absorption was seen in human subjects, a greater magnitude of variability was observed in dogs. For three sets of data, a lag time in gastric emptying was necessary to improve the accuracy of model-generated in vivo blood level profile predictions. In addition to species-associated dissimilarities in drug solubilization due to human versus canine differences in gastrointestinal fluid compositions, the far more rapid intestinal transit time and potential segmental differences in drug absorption needed to be considered during human-canine extrapolation of oral drug and drug product performance. Through the use of mechanistic models, the data generated in the human and canine studies contributed insights into some aspects of the interspecies differences to be considered when extrapolating oral bioavailability/formulation effect data between dogs and humans.

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Characterisation of the Pore Structure of Functionalised Calcium Carbonate Tablets by Terahertz Time-Domain Spectroscopy and X-ray Computed Microtomography

Abstract

Novel excipients are entering the market to enhance the bioavailability of drug particles by having a high porosity and thus providing a rapid liquid uptake and disintegration to accelerate subsequent drug dissolution. One example of such a novel excipient is functionalised calcium carbonate (FCC), which enables the manufacture of compacts with a bimodal pore size distribution consisting of larger inter-particle and fine intra-particle pores. Five sets of FCC tablets with a target porosity of 45% to 65% were prepared in 5% steps and characterised using terahertz time-domain spectroscopy (THz-TDS) and X- ray computed microtomography (XμCT). THz-TDS was employed to derive the porosity using effective medium approximations (EMAs), i.e., the traditional and an anisotropic Bruggeman model. The anisotropic Bruggeman model yields the better correlation with the nominal porosity (R2 = 0.995) and it provided additional information about the shape and orientation of the pores within the powder compact. The spheroidal (ellipsoids of revolution) shaped pores have a preferred orientation perpendicular to the compaction direction causing an anisotropic behaviour of the dielectric porous medium. The results from XμCT confirmed the non-spherical shape as well as the orientation of the pores and it further revealed that the anisotropic behaviour is mainly caused by the inter-particle pores. The information from both techniques provide a detailed insight into the pore structure of pharmaceutical tablets. This is of great interest to study the impact of tablet microstructure on the disintegration and dissolution performance.

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Advancements in the Development and Manufacturing of Nanosuspension Based Drug Products

Several nanoparticulate drug products joined the market in the last decade with commercial success. More recently, generic copies of originator products joined also the market demonstrating attractive and promising business areas. However, strategic drawbacks and technical limitations are nonetheless obvious to extract the inherent capabilities of nanosuspension based drug products. For instance: When should be a nanosuspension approach selected for a poorly soluble compound? Do we have realized the potential of nanosized drug compounds? Do we have elaborated future drug product manufacturing strategies to enable continuous manufacturing and patient centric approaches? The presentation will provide an overview on the currently commercialized nanosuspension based drug products, and will mainly focus on the following topics to address current strategic drawbacks and technical limitations:

  • In vitro rank ordering of formulation concepts from enabling technologies at the early stage of development.
  • Perspectives and first successes for drug nanoparticles below 100 nm particle size.
  • Continuous manufacturing of solid oral drug products with flexible dose strength using liquid dispensing and forced drying technology.

Michael Juhnke

Senior Fellow Oral Pharmaceutical Development Novartis AG 

Switzerland 

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Can your innovative biomedical research help astronauts get to Mars? A request for proposals

The newly established Translational Research Institute (TRI) at Baylor College of Medicine seeks innovative and disruptive technologies, techniques and countermeasures to enable and enhance human exploration of deep space. We are soliciting proposals from any US-based biomedical researcher or company, regardless of previous NASA funding.

 

Funding topics of current interest are:

  • Omics capabilities for use during spaceflight missions
  • Long duration medication stability
  • Human brain imaging
  • Inflight surgical capabilities
  • Increasing organisms’ resistance to radiation
  • Pharmaceuticals that preserve muscle mass
  • Inflight production of fresh food
  • Microbiome based therapies for improving health in spaceflight
  • Lymphatic imaging in microgravity

The details of this TRI research announcement (NNJ16ZSA001N-TRI) may be viewed at

https://tinyurl.com/BCM-TRIMar17

 

Proposers must submit a letter of intent through nspires.nasaprs.com by April 10, 2017 in order to submit a full proposal. A pre-proposal webinar, during which TRI management will answer questions regarding the research announcement, will be held on March 23, 2017 and is open to all interested proposers.

 

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The Translational Research Institute (TRI) is funded by a cooperative agreement from NASA to Baylor College of Medicine with consortium partners California Institute of Technology and Massachusetts Institute of Technology. The Institute’s mission is to lead a national effort in translating cutting-edge, emerging terrestrial research into applied space flight and to support human risk-mitigation for exploration missions beyond low Earth orbit. 

 

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Armor Pharma to announce the availability of " ARMOR PHARMA lactose monohydrate 80M

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Continuous Processing of Solid Oral Dose Forms

Traditional concepts of batch processing have given way to new paradigms in continuous processing for the manufacturing solid oral products. This transition from batch manufacture to continuous, flow-through systems requires development of new technologies, devices, procedures, control systems and release strategies. This requires a new understanding of both the theoretical and practical aspects of the most common unit operations and redefines the way products are developed and commercialized. This presentation will provide an overview of the design and development activities within Pfizer that led to the development of continuous processing systems and at the same time adapting them to target commercial products. The examples shown should provide insight to both the conceptual understanding of continuous processing systems and the data-driven approaches that were fundamental to the development of Pfizer’s portable, continuous processing module.

George Sienkiewicz, Ph.D.
Senior Manager
Pfizer Inc.

 

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Ensuring Patient Safety through Appropriate Impurity Evaluation

ABSTRACT: The presence of undetected impurities in drug products can lead to devastating side effects. For example, Diethylene Glycol (DEG) as an impurity has troubled the drug product industry for nearly 75 years. DEG has been used as a low cost but toxic substitute for glycerin and has directly caused the death of hundreds of children and adults. Tragedies such as these are preventable.  The scope of this presentation is to discuss a scientific, collaborative and unbiased approach to the responsible evaluation of pharmaceutical ingredients. The evaluation must begin internally and extend to the outer boundaries of a drug product’s supply chain. A weak approach to the evaluation of ingredient impurities can potentially adulterate the entire chain. Investigation of possible impurities begins with a realistic evaluation of a firm’s manufacturing environment including historical factors and inherent properties of the product and its raw materials. Furthermore, the investigation must include in depth evaluations of raw material manufacturing paths and supplier questionnaires. These factors must be compiled to design a comprehensive impurity profile that, when combined with proper analytical techniques, supports industry’s assurance of patient safety.

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Medical Marijuana: Improving stability with novel delivery methods

ABSTRACT: Medical Marijuana products can be one of most promising therapeutics in the near future. However, its pharmaceutical use poses many formulation challenges: absortion, dosage variability, strain differences, extraction methods makes it potentially unpredictable. The purest and more effective forms of THC (99.9%) are highly unstable due to oxidation on room air, AXIM Biotechnologies patented a micro-encapsulation technology using gum base that preserves its integrity while ensuring drug delivery in 20 minutes or less (compared to previous efforts where chewing gum retained up to 50% of the APIs since cannabinoids are highly hydrophobic and lipophilic, they were adhering too much to the gum base and not being released properly). 

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Understanding the Filmcoating Process

ABSTRACT: The operator of a filmcoating process typically has no control over the properties of tablet core and filmcoating material. Thorough understanding of the flmcoating process is therefore essential for the quality of the final, coated product. This presentation will map out the variables in the coating process and show their interdependence. Guidance will be given for a rational set up of coating processes. 

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The biopharmaceutical classification system of excipients - Introduction to Article

Teófilo Vasconcelos1,2,3,4, Sara Marques2,5 & Bruno Sarmento3,4,6

 

1BIAL-Portela & Cª, S.A. À Avenida da Siderugia Nacional, Trofa, Portugal; 2Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal; 3I3S – Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal; 4INEB – Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal; 5CIBIO/InBIO-UP – Research Centre in Biodiversity & Genetic Resources, University of Porto, Vairão, Portugal; 6CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde & Instituto Universitário de Ciências da Saúde, Gandra, Portugal 

In the last couple of decades the pharmaceutical excipients industry has been highly active pursuing new excipients able to overcome the market needs. Among these needs are the highly specific functional excipients for drug delivery and excipients able to interfere with our biological barriers. Regarding the later, the development of excipients able to interfere with the intestinal metabolism and efflux mechanisms were among the top priorities [1]. This text will focus on the excipients able to interfere with our biological systems in the gastrointestinal tract.

At this stage it is possible to denote that a huge progress was made and a lot of new excipients were developed. Among these, polymeric surfactants were the ones presenting more potential to interfere and affect our intestinal biological mechanisms and thus improving drug performance [2].

Intestinal defense mechanisms, such as intestinal metabolism and efflux mechanisms are playing an important role in decreasing the bioavailability of drugs, particularly relevant in drugs belonging to the BCS classes II, III and IV, which represent the majority of drugs currently under development [3].

Intestinal metabolism mechanisms refer to enzymes present in intestinal mucosa. Cytochrome P450 (CYPs) are of particular importance, being responsible for the majority of phase I drug metabolism reactions. From these, CYP3A and CYP2C are the most representative in the intestinal mucosa, in which, CYP3A4, CYP3A5 and CYP2C9 are the most representative in this order of relevance[4]. Intestinal efflux transporters include, P-glycoprotein (P-gp), multidrug resistance proteins (MRP2), organic anion-transporting polypeptide (OATP) and breast cancer resistance protein (BCRP) as most important [5].

Recently a biopharmaceutical classification system of excipients (BCSE) was proposed as tool for better understanding of excipients biological mechanisms. This classification can be a key element for formulators and regulatory authorities [2].

The BCSE classifies the excipients in four classes depending on its ability to interfere with metabolization and /o or intestinal efflux [2].

The BCSE class I includes excipients that do not affect with intestinal metabolism and efflux mechanisms. BCSE class II include excipients that can interfere in the intestinal metabolism mechanisms and not in the intestinal efflux. BCSE class III, only interfere with intestinal efflux mechanisms and not with metabolization mechanisms. The BCSE class IV, include excipients that affect with both intestinal metabolism and efflux mechanisms [2].

Formulators can use this classification to better select the excipients present on the formulation in order to maximize their drugs potential during development phase. These would allow a rationale selection of excipients based not only on the drug and dosage form properties but also including the biological impact of excipients. For instance, drugs that present highly intestinal metabolization, may be formulated with excipients from BCSE classes II or IV, which are able to interfere and reduce its metabolization and therefore maximizing its bioavailability. Generally, it is possible to state that excipients from BCSE class I will present low biological beneficial effect. Excipients form BCSE classes II and III will present biological beneficial effected depending on the drug properties. The excipients belonging to BCSE class IV are the ones with more potential to provide biological beneficial effects on the formulation [2].

At same time, the BCSE can be an important instrument for regulatory agencies. It would allow agencies to better manage the safety, quality and efficacy risks associated to the use of excipients. This is particularly relevant considering the increase amount of generic products. Formulations containing excipients form BCSE class I present low risk. Formulations with excipients form BCSE class II and III moderate risk depending on the API properties. The higher risk would be associated to excipients BCSE class IV [2].

Unfortunately and despite the advance in the excipients field there is still a huge gap between in vitro evidence of biological interference of excipients and it in vivo impact. This is mainly due to the lack of specific in vitro models for different biological mechanisms but also due to an absence of specific inhibitors since most of them, interfere with different biological mechanisms at same time. Another current limitation is the translation of in vitro data to in vivo data due to formulation translation constrains, such as unfeasible dosage weight or unacceptable amount of surfactants due to toxicity [2,6].

Despite these limitations, the potential of excipients to interact with our biological barriers is unquestionable and should be subject of a deeply scrutiny [2].


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1.   References

1.              Loftsson T. Excipient pharmacokinetics and profiling. Int J Pharm, 480(1-2), 48-54 (2015).

2.              Vasconcelos T, Marques S, Sarmento B. The biopharmaceutical classification system of excipients. Ther Deliv, 8(2), 65-78 (2017).

3.              Vasconcelos T, Marques S, das Neves J, Sarmento B. Amorphous solid dispersions: Rational selection of a manufacturing process. Adv Drug Deliv Rev, 100, 85-101 (2016).

4.              Ren X, Mao X, Si L et al. Pharmaceutical excipients inhibit cytochrome P450 activity in cell free systems and after systemic administration. Eur J Pharm Biopharm, 70(1), 279-288 (2008).

5.              Estudante M, Morais JG, Soveral G, Benet LZ. Intestinal drug transporters: an overview. Adv Drug Deliv Rev, 65(10), 1340-1356 (2013).

6.              Cornaire G, Woodley J, Hermann P, Cloarec A, Arellano C, Houin G. Impact of excipients on the absorption of P-glycoprotein substrates in vitro and in vivo. Int J Pharm, 278(1), 119-131 (2004).

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Vaccine Excipient & Media Summary -  Excipients Included in U.S. Vaccines, by Vaccine

In addition to weakened or killed disease antigens (viruses or bacteria), vaccines contain very small amounts of other ingredients – excipients or media.

Some excipients are added to a vaccine for a specific purpose. These include:

Preservatives, to prevent contamination. For example, thimerosal.

Adjuvants, to help stimulate a stronger immune response. For example, aluminum salts.

Stabilizers, to keep the vaccine potent during transportation and storage. For example, sugars or gelatin.

Others are residual trace amounts of materials that were used during the manufacturing process and removed. These include: Cell culture materials, used to grow the vaccine antigens. For example, egg protein, various culture media.

Inactivating ingredients, used to kill viruses or inactivate toxins. For example, formaldehyde.

Antibiotics, used to prevent contamination by bacteria. For example, neomycin.

The following table lists all components, other than antigens, shown in the manufacturers’ package insert (PI) for each vaccine. Each of these PIs, which can be found on the FDA’s website (see below) contains a description of that vaccine’s manufacturing process, including the amount and purpose of each substance. In most PIs, this information is found in Section 11: “Description.”

 

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Implementation strategy of ICH Q3D guideline

Introduction

The purpose of this document is to address specific considerations to enable the practical implementation of ICH Q3D Guideline for Elemental Impurities in the European Union. It is intended to provide guidance for Applicants/MAHs, drug product, drug substance and excipient manufacturers, as well as regulators. In addition to new applications, it will also apply to variations to existing authorised medicinal products.

Guideline

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A Review of NSF / IPEC / ANSI 363 GMP Standard for Pharmaceutical Excipients – Findings and Best Practices

ABSTRACT: Two year look back at the status of the NSF / IPEC / ANSI 363 GMP Standard for Pharmaceutical Excipients. What are we seeing as a certification body including best practices around risk assessment, quality improvement, the role of management and feedback from companies that have worked to meet the requirements of this GMP standard?

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Fingerprinting Biologics Drugs Using Drop Coat Deposition Confocal Raman (DCDCR) Spectroscopy

ABSTRACT: Counterfeit drugs pose a significant and fast-growing threat to public health and safety. The incident of counterfeit Avastin® in the United States demonstrates the vulnerability of the supply chain even in developed countries. Government health agencies and pharmaceutical manufacturers are finding ways to fight counterfeit and substandard drugs by identifying them from manufacturing, throughout the supply chain, and eventually when they reach the public in the retail pharmacies.  In 2009, Partnership for Safe Medicines (PSI) reported 1,700 counterfeiting incidences worldwide out of which 60 incidences were biologics, compared to only 10 incidences in 2006. With the recent FDA guideline for biosimilar approval and the counterfeit Avastin® reported in the United States, it is becoming increasingly important that pharmaceutical companies find ways to rapidly fingerprint and detect counterfeit biologics.  Counterfeit biologics are, in a way, difficult to detect since they are administered by injection (white powder or clear liquid) and cannot be distinguished by smell, taste, and appearance. This, along with the sizeable cost, makes counterfeiting biologics an attractive illegal business. This presentation demonstrates that Drop Coat Deposition (DCD) technique for the biologics drug product sample, coupled with confocal Raman spectroscopy can be effectively used to fingerprint protein based biologics pharmaceuticals. These spectral fingerprints can be used routinely to screen and detect biologics counterfeits.

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Sugar Spheres: Improving clinical effectiveness with Multiparticulate drug delivery systems

ABSTRACT: The upcoming of biopharmacy in the 1950s resulted in various delayed, prolonged, sustained, extended, repeat action or in one word controlled release formulations. The establishment of those formulations is strongly connected to the development of multiparticulate drug delivery systems as they are especially suitable for achieving controlled release formulations with low risk of dose dumping while offering high flexibility in blending and outstanding reproducibility. The drug release and thus clinical effectiveness of multiparticulate drug delivery systems depends on various factors including especially the carrier. Sugar spheres are widely used as carriers due to the fact that they combine important characteristics in respect to pharmaceutical technology. Their high sphericity results in unique flow abilities which maximize the usability in filling and dosing processes while their high usability in coating processes offer great opportunities for multilayer applications often used in controlled release formulations. In respect to patient related facts much emphasis is being laid on multiparticulate drug delivery systems showing increased bioavailability, reduced risk of systemic toxicity and reduced risk of local irritation in preference to single unit (monolithic) systems. In conclusion multiparticulate dosage forms were and will be the first choice for the development of demanding controlled release formulations.

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2017 EXCIPACT STANDARDS REVISION – STAKEHOLDER CONSULTATION OPENS

The EXCiPACT Board commissioned a project team to undertake a revision of the EXCiPACT standards to align them to ISO 9001:2015 and ISO/IEC 17021-1:2015 without change or enhancement of any individual requirements, other than to correct for errors in the original publication. The draft revision has been completed and is now available for public comment via a Review Template, mandatory for the submission of comments. Links to both documents are:

ONLY COMMENTS RECEIVED BY FRIDAY 5th MAY 2017, ON A CORRECTLY COMPLETED REVIEW TEMPLATE WITH PROPOSED ALTERNATIVE WORDING WILL BE CONSIDERED. ANY OTHER FORM OF COMMENT OR FAILURE TO PROPOSE ALTERNATIVE WORDING, OR ANONYMOUS COMMENT, WILL BE DISREGARDED.
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Inhaled dry powder mannitol in children with cystic fibrosis: A randomised efficacy and safety trial

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Inhaled mannitol has beneficial effects on lung function, mucociliary clearance, quality of life and sputum properties. This trial examined the efficacy of inhaled mannitol in children with cystic fibrosis (CF).

Methods

The efficacy of inhaled mannitol in children with CF aged 6–17 years was assessed in a phase 2, randomised, placebo-controlled crossover study. Subjects were randomly assigned to mannitol 400 mg every 12 h or matching placebo for 8 weeks, followed by an 8 week washout and an 8 week period with the alternate treatment. The primary endpoint was the absolute change from baseline in ppFEV1 (percent predicted FEV1).

Results

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Conclusions

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Controlled release of insulin from folic acid-insulin complex nanoparticles

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Thermoplastic starch: improving their barrier properties

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Amorphous is not always better—A dissolution study on solid state forms of carbamazepine

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Modulation of microenvironmental pH for dual release and reduced in vivo gastrointestinal bleeding of aceclofenac using hydroxypropyl methylcellulose-based bila

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Continuous direct pelletization technologies and other innovative formulation solutions?

Meet Glatt Pharmaceutical Services

@2nd EUROPEAN CONFERENCE on Pharmaceutics - Novel dosage forms & innovative technologies - 3

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Abstract

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