Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
Vol. 14, No. 1, 2015, pp. 21-26
Bioline Code: pr15004
Full paper language: English
Document type: Research Article
Document available free of charge
Tropical Journal of Pharmaceutical Research, Vol. 14, No. 1, 2015, pp. 21-26
© Copyright 2015 - Tropical Journal of Pharmaceutical Research
Enhancement of Solubility and Bioavailability of Candesartan Cilexetil using Natural P-Glycoprotein Inhibitors|
Zulal, Noor Ahmad & Lakshmi, P.K.
Purpose: To enhance the otherwise poor solubility and bioavailability of candesartan cilexetil (CDS).
Methods: This study involved enhancing drug solubility by various solid dispersion (SD) methods. The
drug: carrier ratio was as follows: for urea (1:2, 1:4 and 1:6; for polyethylene glycol 6000 (PEG, 1:2 and
1:4, 1:8); and mannitol (1:2, 1:4 and 1:6. Piperin and quercetin (natural P-glycoprotein inhibitors) were
used as bioavailability enhancers. Bioavailability stdies were carried out in a rat model with the SDs
formulated in a suspension form and administered by the oral route.
Results: All the carriers enhanced drug dissolution in water 2 to 4-fold depending on drug/carrier ratio.
Release kinetics from solid dispersions made with mannitol showed zero order drug release. Urea and
PEG 6000-based solid dispersions showed 1st order drug release kinetics. FTIR studies confirmed
transformation to an amorphous form of CDS in mannitol solid dispersion; this was buttressed by
release kinetic studies. Bioavailability of the drug in the animals was enhanced by 27 and 68 % when
quercetine and piperine, respectively, were incorporated.
Conclusion: Formation of solid dispersion enhances the solubility and bioavailability of CDS when
natural P-glycoprotein inhibitors such as piperin and quercetin are incorporated as enhancers.
Solid dispersion; Candesartan; Cilexetil; Bioavailability; P- Glycoprotein; Piperin; Quercetin
Alternative site location: http://www.tjpr.org