Microenvironmental pH-modified Amisulpride-Labrasol matrix tablets: development, optimization and in vivo...

Amisulpride (AMS) is atypical antipsychotic with a weak basic nature (pKa 9.37), which results in low solubility in the high pH of the intestine. It is also recognized as a substrate of P-glycoprotein efflux pump. Both factors lead to its low oral bioavailability (48%). The daily dose of AMS is between 200 and 1200 mg to be taken in divided doses which compromise patient compliance. Therefore, controlled release formulation of AMS is of clinical significance. AMS was formulated into matrix tablets containing Labrasol, P-glycoprotein efflux inhibitor, and a penetration enhancer, using direct compression technique. The tablets were prepared according to 2¹·4¹ factorial design using two polymers, namely, HPMC and Carbopol 934 at four concentrations (20%, 30%, 40%, 50%). Percentage AMS released after 2 h (Q_2hr%) and 8 h (Q_8hr%) were chosen as dependent variables. Two acidic pH modifiers (fumaric acid and tartaric acid) at two levels (15% and 30%) were incorporated in the tablet according to 2² factorial design. All formulae with acidic pH modifier had similarity factor (f₂) ≥ 50 proving the pH independent release of AMS. The pharmacokinetic study in rabbits revealed 30% enhancement of the oral absorption AMS imparted by the pH-modified matrix tablet containing Labrasol. Graphical abstract.