Abstract
Amisulpride (AMS), a BCS Class II antipsychotic and antiemetic, suffers from poor aqueous solubility, limiting its oral bioavailability and onset of action. This study aimed at systematically compare Soluplus®-mediated dissolution enhancement of AMS via solid dispersion (SD) and nanomicelle (NM), and to incorporate the optimized formulations into oral fast-dissolving films (OFDFs) for rapid antiemetic delivery. A D-optimal response surface methodology (RSM) was employed to optimize SD and NM formulations, with Soluplus® as the hydrophilic carrier at varying drug-to-polymer ratios (1:4, 1:9, and 1:19) and solvent volumes. The optimized SD (1:4 in 10.4 mL) and NM (1:4.5 in 20 mL) formulations were characterized by DSC, PXRD, FTIR, and SEM, confirming complete amorphization and hydrogen bonding between AMS and Soluplus®. Both optimized formulations were then loaded into OFDFs using PVA as the film-forming polymer. In vitro dissolution of the films revealed that NM-based films achieved 100% drug release within 25 minutes, significantly faster than SD-based films, which reached near-complete release (~95-99%) by 60 minutes. Despite these differences in release kinetics, particle size analysis of the dissolution media showed that both systems formed large aggregates (≈500 nm), and ultrafiltration confirmed near-zero free drug in the filtrate, indicating a supersaturation-driven micellar reservoir mechanism rather than true molecular dissolution. These findings demonstrate that while both SD and NM systems effectively enhance AMS dissolution, the NM-based OFDF provides superior rapid release kinetics, making it a promising platform for fast-onset antiemetic therapy. The study also questions the sole reliance on dissolution profiles for comparing nanocarrier systems, highlighting the importance of mechanistic characterization.
| Has the manuscript been published | not published |
|---|---|
| Intend to be published in the IJPS ? | NO |
