Development of Gastroretentive Floating Pellets to Enhance the Oral Bioavailability of Luracidone Hydrochloride

Luracidone hydrochloride exhibits pH-sensitive solubility, which limits its absorption and results in poor oral bioavailability. To address this problem, the present study focused on the formulation of gastro retentive floating pellets of luracidone hydrochloride using the extrusion-speronization technique to enhance gastric retention, solubility, and plasma concentration. The 33 Box-Behnken design was applied to optimize the formulation batch. For that, the levels of HPMC K100 (X1), ethyl cellulose (X2), and spheronization speed (X3) were varied, and their influence was evaluated on aspect ratio (Y1), floating time (Y2), and in vitro % drug release (Y3). The observed optimized batch was subsequently coated with a 5 % ethyl cellulose and subjected to a comprehensive physicochemical evaluation with % drug release and in vivo pharmacokinetic assessment. The drug release data observed that the coated luracidone hydrochloride pellets release the drug over 18 h, whereas the uncoated pellets release up to 12 h. The ethyl cellulose coating also improved the buoyancy, which minimizes dose dumping and improves the absorption window of luracidone hydrochloride in the upper GI tract. The relative oral bioavailability of uncoated and coated pellets was significantly higher, up to 5-fold and 7-fold, respectively, compared to pure luracidone hydrochloride. It strongly supports the hypothesis that coated luracidone hydrochloride gastro retentive floating pellets could enhance oral bioavailability instead of pure lurasidone hydrochloride. Keywords Lurasidone hydrochloride, spheronization, gastro retentive pellets, buoyancy, oral bioavailability