Login Register Cart 0
Generic placeholder image

Recent Patents on Drug Delivery & Formulation

Editor-in-Chief

ISSN (Print): 1872-2113
ISSN (Online): 2212-4039

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

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

Author(s): Dipti Srivastava, Zeeshan Fatima*, Chanchal D. Kaur, Sachin L. Tulsankar, Sanap S. Nashik and Dilshad A. Rizvi

Volume 13, Issue 1, 2019

Page: [62 - 69] Pages: 8

DOI: 10.2174/1872211313666190306160116

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.

Keywords: Cocrystal, coformer, candesartan, methyl paraben, powder X-ray diffraction, fourier transform infrared.

« Previous Next »
Graphical Abstract

[1]
Unger T. Pharmacological aspects of candesartan, an effective AT1-receptor blocker. Eur Heart J Suppl 2004; 6(Suppl. H): h11-6.
[2]
Shibouta Y, Inada Y, Ojima M, Wada T, Noda M, Sanada T. Pharmacological profile of a highly potent and long-acting angiotensin II receptor antagonist, 2-ethoxy-1-[[2′-(1H-tetrazol-5-yl) biphenyl-4-yl] methyl]-1H-benzimidazole-7-carboxylic acid (CV-11974), and its prodrug,(+/-)-1-(cyclohexyloxycarbonyloxy)-ethyl 2-ethoxy-1-[[2′-(1H-tetrazol-5-yl) biphenyl-4-yl] methyl]-1H-benzimidazole-7-carboxylate (TCV-116). J Pharmacol Exp Ther 1993; 266(1): 114-20.
[3]
Gurunath S, Nanjwade BK, Patila PA. Enhanced solubility and intestinal absorption of candesartan cilexetil solid dispersions using everted rat intestinal sacs. Saudi Pharm J 2014; 22(3): 246-57.
[4]
Shaikh MS, Avachat MA. Enhancement of solubility and permeability of candesartan cilexetil by using different pharmaceutical interventions. Curr Drug Deliv 2011; 8(4): 346-53.
[5]
Sayyad FJ, Tulsankar SL, Kolap UB. Design and development of liquisolid compact of candesartan cilexetil to enhance dissolution. J Pharm Res 2013; 7(5): 381-8.
[6]
Gao F, Zhang Z, Bu H, Huang Y, Gao Z, Shen J, et al. Nanoemulsion improves the oral absorption of candesartan cilexetil in rats: Performance and mechanism. J Control Release 2011; 149(2): 168-74.
[7]
Nekkanti V, Pillai R, Venkateshwarlu V, Harisudhan T. Development and characterization of solid oral dosage form incorporating candesartan nanoparticles. Pharm Dev Technol 2009; 14(3): 290-8.
[8]
Chi Y, Xu W, Yang Y, Yang Z, Lv H, Yang S. Three candesartan salts with enhanced oral bioavailability. Cryst Growth Des 2015; 15(8): 3707-14.
[9]
Bhandaru JS, Malothu N, Akkinepally RR. Characterization and Solubility Studies of Pharmaceutical Cocrystals of Eprosartan Mesylate. Cryst Growth Des 2015; 15(3): 1173-9.
[10]
Qiao N, Wang K, Schlindwein W, Davies A, Li M. In situ monitoring of carbamazepine–nicotinamide cocrystal intrinsic dissolution behaviour. Eur J Pharm Biopharm 2013; 83(3): 415-26.
[11]
Chadha R, Saini A, Jain DS, Venugopalan P. Preparation and Solid-State Characterization of Three Novel Multicomponent Solid Forms of Oxcarbazepine: Improvement in Solubility through Saccharin Cocrystal. Cryst Growth Des 2012; 12(8): 4211-24.
[12]
Stahly GP. A Survey of Cocrystals Reported Prior to 2000. Cryst Growth Des 2009; 9(10): 4212-29.
[13]
Jones W, Motherwell WDS, Trask AV. Pharmaceutical cocrystals: An emerging approach to physical property enhancement. MRS Bull 2006; 31(11): 875-9.
[14]
Vishweshwar P, McMahon JA, Bis JA, Zaworotko MJ. Pharmaceutical co-crystals. J Pharm Sci 2006; 95(3): 499-516.
[15]
Srivastava D, Fatima Z, Kaur CD. Multicomponent pharmaceutical cocrystals: A novel approach for combination therapy. Mini Rev Med Chem 2018; 18(14): 1160-7.
[16]
Desiraju GR. Supramolecular synthons in crystal engineering- A new organic synthesis. Angew Chem Int Ed Engl 1995; 34(21): 2311-27.
[17]
Qiao N, Li M, Schlindwein W, Malek N, Davies A, Trappitt G. Pharmaceutical cocrystals: An overview. Int J Pharm 2011; 419(1-2): 1-11.
[18]
Nadgoud RK, Vasam S, Makireddy SR, et al. Co-crystal of carfilzomsib with maleic acid and process for the preparation of pure carfilzomib. EP3240575A1 (2017).
[19]
Kocherlakota C, Banda N. Novel co-crystal forms of agomelatine. WO2017115284A1 (2017).
[20]
Tesson ZN, Gordo CE. Cocrystals of lorcaserin. EP3210975A1 (2016).
[21]
Albert E, Andres P, Bevill MJ, Smit J, Nelson J. Cocrystals of progesterone. US9982007B2 (2018).
[22]
Albrecht W, Geier J, Rabe S, Perez PD. Co-crystals of ibrutinib with carboxylic acids. WO2016156127A1 (2016).
[23]
Gonnade RG. Pharmaceutical cocrystals of gefitinib WO2015170345A1 (2015).
[24]
Zhang GG, Henry RF, Borchardt TB, Lou X. Efficient cocrystal screening using solution-mediated phase transformation. J Pharm Sci 2007; 96(5): 990-5.
[25]
Childs SL, Rodriguez-Hornedo N, Reddy LS, Jayasankar A, Maheshwari C, McCausland L. Screening strategies based on solubility and solution composition generate pharmaceutically acceptable cocrystals of carbamazepine. CrystEngComm 2008; 10(7): 856-64.
[26]
Mittapalli S, Mannava MKC, Khandavilli UBR, Allu S, Nangia A. Soluble salts and cocrystals of clotrimazole. Cryst Growth Des 2015; 15(5): 2493-504.
[27]
Goyal P, Rani D, Chadha R. Crystal engineering: A remedy to tailor the biopharmaceutical aspects of glibenclamide. Cryst Growth Des 2018; 18(1): 105-18.
[28]
Bhattacharyya A, Bajpai M. Oral bioavailability and stability study of a self-emulsifying drug delivery system (SEDDS) of amphotericin B. Curr Drug Deliv 2013; 10(5): 542-7.
[29]
Gleiter CH, Morike KE. Clinical pharmacokinetics of candesartan. Clin Pharmacokinet 2002; 41(1): 7-17.
[30]
Sanphui P, Babu NJ, Nangia A. Temozolomide Cocrystals with Carboxamide Coformers. Cryst Growth Des 2013; 13(5): 2208-19.
[31]
Sowa M, Ślepokura K, Matczak-Jon E. Improving solubility of fisetin by cocrystallization. CrystEngComm 2014; 16(46): 10592-601.

Rights & Permissions Print Cite
Article Metrics
82
9
1
© 2024 Bentham Science Publishers | Privacy Policy