Study of surfactant combinations and development of a novel nanoemulsion for minimising variations in bioavailability of ezetimibe.
The present study aimed at developing an optimal nanoemulsion of ezetimibe and evaluating its stability, pharmacodynamic and pharmacokinetic potential. Solubility of ezetimibe was determined in various vehicles. Surfactants and cosurfactants were grouped in two different combinations to construct pseudoternary phase diagrams. Formulations were selected from the o/w nanoemulsion region and were subjected to various thermodynamic stability and dispersibility tests. Optimized formulations were characterized for their percentage transmittance, refractive index, viscosity, droplet size and zeta potential. Release rate of optimized formulations was determined using an in vitro dissolution test. The formulation used for assessment of lipid lowering potential and bioavailability contained Capryol 90 (10%, v/v), Tween 20 (33.33%, v/v), PEG 400 (16.67%, v/v), double distilled water (40%, v/v). The release of drug from the nanoemulsion formulations was extremely significant (p<0.001) in comparison to the drug suspension. More than 60% of the drug was released in the initial 1h of the dissolution study in comparison to the drug suspension. The value of total cholesterol in the group administered with the formulation PF1 was highly significant (p<0.001) with respect to the group administered with the suspension of the drug. The plasma concentration time profile of ezetimibe from nanoemulsion represented greater improvement of drug absorption than the marketed formulation and simple drug suspension. The shelf life of the nanoemulsion was found to be 5.94 years at room temperature. The present study established nanoemulsion formulation to be one of the possible alternatives to traditional oral formulations of ezetimibe to improve its bioavailability.
Bali
Vikas
V
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Ali
Mushir
M
Ali
Javed
J
D000818:Animals; D001384:Azetidines / Q000737:chemistry* / Q000493:pharmacokinetics; D002784:Cholesterol / Q000097:blood; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry; D000069438:Ezetimibe; D008075:Lipoproteins, HDL / Q000097:blood; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry*; D013816:Thermodynamics; D014018:Tissue Distribution
D001384:Azetidines; D004655:Emulsions; D008075:Lipoproteins, HDL; D013501:Surface-Active Agents; D002784:Cholesterol; D000069438:Ezetimibe