Development of novel amisulpride-loaded solid self-nanoemulsifying tablets: preparation and pharmacokinetic evaluation in rabbits.

OBJECTIVE: The current investigation is focused on the formulation and in vivo evaluation of optimized solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of amisulpride (AMS) for improving its oral dissolution and bioavailability.

METHODS: Liquid SNEDDS (L-SNEDDS) composed of Capryol™ 90 (oil), Cremophor(®) RH40 (surfactant), and Transcutol(®) HP (co-surfactant) were transformed to solid systems via physical adsorption onto magnesium aluminometasilicate (Neusilin US2). Micromeretic studies and solid-state characterization of formulated S-SNEDDS were carried out, followed by tableting, tablet evaluation, and pharmacokinetic studies in rabbits.

RESULTS: Micromeretic properties and solid-state characterization proved satisfactory flow properties with AMS present in a completely amorphous state. Formulated self-nanoemulsifying tablets revealed significant improvement in AMS dissolution compared with either directly compressed or commercial AMS tablets. In vivo pharmacokinetic study in rabbits emphasized significant improvements in tmax, AUC(0-12), and AUC(0-∞) at p < .05 with 1.26-folds improvement in relative bioavailability from the optimized self-nanoemulsifying tablets compared with the commercial product.

CONCLUSIONS: S-SNEDDS can be a very useful approach for providing patient acceptable dosage forms with improved oral dissolution and biovailability.