Recent strategies in spray drying of poorly water-soluble drugs to enhance bioavailability


Poorly water-soluble drugs are a significant and ongoing issue for the pharmaceutical industry. An overview of recent developments for the preparation of spray-dried delivery systems is presented. Examples include amorphous solid dispersions, spray dried dispersions, microparticles, nanoparticles, surfactant systems and self-emulsifying drug delivery systems. Several aspects of formulation are considered, such as pre-screening, choosing excipient(s), the effect of polymer structure on performance, formulation optimisation, ternary dispersions, fixed-dose combinations, solvent selection and component miscibility. Process optimisation techniques including nozzle selection are discussed. Comparisons are drawn with other preparation techniques such as hot melt extrusion, freeze drying, milling, electro spinning and film casting. Novel analytical and dissolution techniques for the characterization of amorphous solid dispersions are included. Progress in understanding of amorphous supersaturation or recrystallisation from solution gathered from mechanistic studies is discussed. Aspects of powder flow and compression are considered in a section on downstream processing. Overall, spray drying has a bright future due to its versatility, efficiency and the driving force of poorly soluble drugs.


Prospects for the Future

Spray drying is enjoying great popularity in research as a tool for creating particles with enhanced bioavailability. Given the high number of drugs experiencing poor solubility it is likely that research, development and commercial use of spray drying will continue to increase. Commercial technology is improving. Advanced rotary atomisers are now available that are no longer prone to high maintenance costs(Lonergan, n.d.). A direct drive magnetic spray machine (MSM) is now in production(Khatri et al., 2015). Bend research have patented the use of a pressure nozzle and diffuser plate for producing pharmaceutical particles with larger particle size Distribution (Beyerinck et al., 2014). As mentioned in the section on downstream processing, this is important for flow, die fill, compression and tablet uniformity. Hovione have filed a patent concerning continuous production of particles(Fonseca et al., 2016). Hightemperature spray drying using a flash nozzle has also been patented by Bend research(Friesen et al., 2016). Process analytical technologies such as FBRM, turbidimetry,

viscosimetry, laser diffraction, NIR and mass spectroscopy can reduce timescales for production quality control(Burggraeve et al., 2013; Chan et al., 2008). Regulatory pressures are likely to drive a move away from toxic solvents, over time.

Supercritical CO2 technology represents a move away from toxicity, but several issues such as solubility need to be addressed for this to become more mainstream. Even ppm levels of dichloromethane are undesirable, so ethanol and isopropyl alcohol are more likely to be used if they fully solubilise all components(Paudel et al., 2013). An information age consumer is also more likely to buy a medicine that can be marketed as ‘greener’ than the consumers of yesterday. Such information is becoming increasingly readily available with the continued rise in information technology and can be exploited as a marketing tool.

Future innovations are likely to come from within industrial pharmaceutical research groups, but also from parallel industries. Food and cosmetic sectors are fast-paced dynamic environments with differing regulatory requirements to pharma. Academia-industry collaborations are particularly useful sources of new ideas and academic research is not

nearly as hampered by regulatory constraints. Due to the population of lipophilic drugs populating the pharmaceutical pipeline and the preference for oral solid dosage, further breakthroughs are very likely. Future publications are

likely to focus on many of the areas addressed by this review, particularly in the areas of understanding stability, manufacturing, dissolution, pharmacokinetics and downstream processing.


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Schematic representation of amorphous solid dispersions, microparticles, nanoparticles, Ternary ASD and Self-emulsifying drug delivery systems prepared by spray drying.
Recent strategies in spray drying