Title:Pharmaceutical Cocrystal: A Novel Approach to Tailor the Biopharmaceutical Properties of a Poorly Water Soluble Drug
VOLUME: 13 ISSUE: 1
Author(s):Dipti Srivastava, Zeeshan Fatima*, Chanchal D. Kaur, Sachin L. Tulsankar, Sanap S. Nashik and Dilshad A. Rizvi
Affiliation:Amity Institute of Pharmacy, Amity University Uttar Pradesh, Lucknow Campus, Uttar Pradesh 201313, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Lucknow Campus, Uttar Pradesh 201313, Sri Rawatpura Institute of Pharmacy, Kumhari, Durg, Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, Department of Pharmacology, Era's Lucknow Medical College and Hospital, Sarfarazganj Lucknow, Uttar Pradesh 226003
Keywords:Cocrystal, coformer, candesartan, methyl paraben, powder X-ray diffraction, fourier transform infrared.
Abstract:
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.
Conclusion: The prepared cocrystal was found to be relatively more soluble than the pure drug and
also showed an enhanced oral bioavailability as compared to the pure drug.