Nanocarrier for the enhanced bioavailability of a cardiovascular agent: in vitro, pharmacodynamic, pharmacokinetic and stability assessment.
The goals of the current study were to develop and characterize a nanoemulsion of ezetimibe, evaluate its stability, lipid lowering and pharmacokinetic profile. Solubility of the drug was estimated in various oils and surfactants. Existence of nanoemulsion region was confirmed by plotting phase diagrams. Various thermodynamic stability and dispersibility tests were performed on the formulations chosen from phase diagram. Percentage transmittance, refractive index, viscosity, droplet size and zeta potential of the optimized formulations were determined. Dialysis bag method was employed to study the release rate. The formulation selected for bioavailability estimation contained Capryol 90 (10%, v/v), Crempophor EL (11.25%, v/v), Transcutol(®) P (33.75%, v/v), and double distilled water (45%, v/v). The release rate from the nanoemulsion was highly significant (p<0.001) in contrast to the drug suspension. The level of total cholesterol in the group receiving nanoemulsion CF1 was found to be highly significant (p<0.001) in comparison to the group receiving drug suspension. Bioavailability studies in rats revealed superior absorption of ezetimibe from nanoemulsion as compared to the marketed formulation and drug suspension. The shelf life of the nanoemulsion was estimated to be 18.53 months. The present study corroborated nanoemulsion to be a promising choice to improve the bioavailability of ezetimibe.
Bali
Vikas
V
Department of Pharmaceutics, Hamdard Nagar, Jamia Hamdard, New Delhi 110062, India.
Ali
Mushir
M
Ali
Javed
J
D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D001384:Azetidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions; D000069438:Ezetimibe; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties
D000924:Anticholesteremic Agents; D001384:Azetidines; D002317:Cardiovascular Agents; D004337:Drug Carriers; D004655:Emulsions; D002784:Cholesterol; D000069438:Ezetimibe