Pharmaceutical Cocrystal: A Novel Approach to Tailor the Biopharmaceutical Properties of a Poorly Water Soluble Drug

摘要

Aim and Background: The present study reports the formation of a cocrystal of candesartanwith the coformer methyl paraben, its characterization and determination of its bioavailability.Candesartan is a poorly water-soluble drug having an anti-hypertensive activity. The recent patents onthe cocrystals of the drugs Progesterone (US9982007B2), Epalrestat (EP2326632B1), Gefitinib(WO2015170345A1), and Valsartan (CN102702118B) for enhancement of solubility, helped inselection of the drug for this work.Methods: Candesartan cocrystal was prepared by solution crystallization method. The formation of anew crystalline phase was characterized by Differential Scanning Calorimetry (DSC), Fourier TransformInfrared (FTIR) and Powder X-ray Diffraction (PXRD) studies. Saturation solubility studies werecarried out in ethanol: water (50:50 % v/v) mixture. The dissolution studies were conducted in 900 mlof phosphate buffer at pH 7.4(I.P.) with 0.7% w/w of Tween 20 at 50 rpm, maintained at a temperatureof 37±0.5°C in a USP type II dissolution apparatus. The pharmacokinetic behavior of candesartan andits cocrystal was thereof investigated in male Wistar rats.Results: There was 6.94 fold enhancement in the solubility of candesartan after its cocrystallization.The dissolution profile of the cocrystal exhibited significant improvement in solubility at 60 and 120minutes and it remained stable in ethanol: water (50:50%v/v) mixture for 48 h as confirmed by PXRDstudies. The AUC0-24of the cocrystal was found to be increased by 2.9 fold in terms of bioavailabilityas compared to the pure drug.