Design Development Characterization and Evaluation of Cocrystals of Some Poorly Water Soluble Drugs

Abstract

Pharmaceutical cocrystals of few BCS class II drugs were prepared using hydrogen bond interactions and proved their enhanced physicochemical properties thereby improved oral bioavailability. Cocrystals of two antihypertensive drugs (EM and CAR) and one over active bladder treatment drug MEB were prepared using LAG and slurry conversion methods. EM cocrystals were prepared using GRAS coformers such as succinic acid (SUC), Salicylic acid (SAL) and P- amino benzoic acid (PABA) using hydrogen bond interactions. Preliminary investigation using DSC and XRPD proved the formation of new solid phases and spectroscopic analysis confirms the formation of EM cocrystals using carboxylic- carboxylic interactions. In case of CAR cocrystals SAC and HYD were used as coformers. Investigation using DSC and XRPD confirmed the formation of new crystalline and solid phases and spectral analysis confirms the formation of CAR cocrystals using amino- amino and amino- hydroxyl interactions. MEB cocrystals were prepared using SAC as coformer and confirmed using DSC, XRPD and spectral analysis. All the three drugs were evaluated for physicochemical properties and they showed good enhancement of the solubility and dissolution behavior than the pure APIs. They also showed improved stability at both elevated temperatures and long time (24 h) exposure to aqueous medium. Relative oral bioavailability of EM cocrystal prepared using SUC as coformer showed 3.5 fold enhancements whereas CAR and MEB showed 1.5 fold enhancement in the relative oral bioavailability using HYD and SAC as coformers. Thus the cocrystallization technique was found to be a suitable tool for developing new solid forms for the enhancement of the physicochemical properties of the BCS class II drugs. newline