Fabrication and Characterization of Amisulpride Nanofibers for Enhanced Oral Pharmacodynamic Properties

Background: Buccal route for drug administration has several advantages over oral route, such as improved systemic bioavailability via avoidance of first-pass metabolism and drug degradation in the gastro-intestinal tract. This work aims to improve the dissolution of amisulpride, anti-psychotic drug, employing nanofibers strategy through the development of fast dispersible oral films for buccal drug administration. Methods: Drug-loaded polymeric nanofibers were prepared with or without surfactants. Poly(vinylpyrrolidone) and poly(vinyl alcohol) were used as film former, while Poloxamer-188 and Cremophor® RH 40 were selected as surfactants. The film prepared by solvent casting was also prepared for comparison. Nanofiber mats were characterized by scanning electron microscopy (SEM), thickness and in vitro drug release. The optimized nanofibers mat was further characterized using differential scanning calorimetry (DSC), X-ray diffraction (XRD), pH value, disintegrating time and folding endurance. In vivo evaluation of the antidepressant effect was performed using forced swim test. Results: Nanofibers formation was confirmed by SEM. The average diameter ranged from 228.3±85.6 nm to 502.1±90 nm. In vitro dissolution reflected improved amisulpride dissolution from nanofibers compared to unprocessed drug. Cremophor® RH 40 was superior to Poloxamer-188 with a 4-fold increment in the percentage drug released after 5 min. Physical characterization indicated reduced drug crystallinity with suggested polymorphic transformation. The in vivo pharmacodynamic evaluation of the optimized nanofibers (using albino rats) indicated 2-fold reduction in the duration of immobility. Conclusion: Oral film for buccal administration employing nanofibers strategy was a useful tool to increase amisulpride dissolution, with subsequent improvement in bioavailability.