Amorphous Solid Dispersion of Furosemide as a Sublingual Bioadhesive Film

Abstract: Administered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving FUR based film has been developed and evaluated in order to optimize the bioavailability of FUR by increasing solubility and guaranteeing a good dissolution reproducibility. The Differential Scanning Calorimetry (DSC) analyses confirmed that the film prepared using the solvent casting method entrapped FUR in the amorphous state. As a solid dispersion, FUR increases its solubility up to 28.36 mg/mL. Drug content, thickness, and weight uniformity of film were also evaluated. The measured Young’s Modulus, yield strength, and relative elongation of break percentage (EB%) allowed for the classification of the drug-loaded film as an elastomer. Mucoadhesive strength tests showed that the force to detach film from mucosa grew exponentially with increasing contact time up to 7667 N/m2. FUR was quickly discharged from

the film following a trend well fitted with theWeibull kinetic model. When applied on sublingual mucosa, the new formulation produced a massive drug flux in the systemic compartment. Overall, the proposed sublingual film enhances drug solubility and absorption, allowing for the prediction of a rapid onset of action and reproducible bioavailability in its clinical application.

Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability
Viviana De Caro 1,* , Alessia Ajovalasit 2, Flavia Maria Sutera 3 , Denise Murgia 1 ,
Maria Antonietta Sabatino 2 and Clelia Dispenza 2,4
1 Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF),
Università degli Studi di Palermo, Palermo, PA 90123, Italy;
2 Dipartimento dell'Innovazione Industriale e Digitale, Ingegneria Chimica, Gestionale, Informatica,
Meccanica, Università degli Studi di Palermo, Palermo, PA 90128, Italy; (A.A.); (M.A.S.); (C.D.)
3 SiSaf Ltd, Innovation Centre, Northern Ireland Science Park, Queen’s Island, Belfast BT3 9DT, UK;
4 Consiglio Nazionale delle Ricerche, Istituto di Biofisica–UOP Palermo, Palermo, PA 90146, Italy
* Correspondence:; Tel.: +39-091-23891926
Academic Editor: Thomas Rades
Received: 26 May 2017; Accepted: 19 June 2017; Published: 24 June 2017
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