Dipti Srivastava, Zeeshan Fatima*, Chanchal D. Kaur, Sachin L. Tulsankar, Sanap S. Nashik and Dilshad A. Rizvi Pages 62 - 69 ( 8 )
Aim and Background: The present study reports the formation of a cocrystal of candesartan with 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 on the cocrystals of the drugs Progesterone (US9982007B2), Epalrestat (EP2326632B1), Gefitinib (WO2015170345A1), and Valsartan (CN102702118B) for enhancement of solubility, helped in selection of the drug for this work.
Methods: Candesartan cocrystal was prepared by solution crystallization method. The formation of a new crystalline phase was characterized by Differential Scanning Calorimetry (DSC), Fourier Transform Infrared (FTIR) and Powder X-ray Diffraction (PXRD) studies. Saturation solubility studies were carried out in ethanol: water (50:50 % v/v) mixture. The dissolution studies were conducted in 900 ml of phosphate buffer at pH 7.4(I.P.) with 0.7% w/w of Tween 20 at 50 rpm, maintained at a temperature of 37±0.5°C in a USP type II dissolution apparatus. The pharmacokinetic behavior of candesartan and its 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 120 minutes and it remained stable in ethanol: water (50:50%v/v) mixture for 48 h as confirmed by PXRD studies. The AUC0-24of the cocrystal was found to be increased by 2.9 fold in terms of bioavailability as compared to the pure drug.
Cocrystal, coformer, candesartan, methyl paraben, powder X-ray diffraction, fourier transform infrared.
Department Of Pharmaceutics, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Lucknow Camous, Department Of Pharmaceutical Chemistry, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Lucknow Camous, Department Of Pharmaceutics, Sri Rawatpura Institute of Pharmacy, Kumhari, Department Of Pharmaceutics and Pharmacokinetics, Division, CSIR-Central Drug Research Institute, Lucknow, Department Of Pharmaceutics and Pharmacokinetics, Division, CSIR-Central Drug Research Institute, Lucknow, Department of Pharmacology, Era's Lucknow Medical College and Hospital, Sarfarazganj Lucknow, Uttar Pradesh 226003