Self-nanoemulsifying granules of ezetimibe: Design, optimization and evaluation

Self-nanoemulsifying granules (SNGs) were formulated with the objective of enhancing the bioavailability of the ezetimibe. Various modified oils, surfactant and cosurfactant mixtures were used and composition of self-nanoemulsifying system (SNS) was optimized. SNS diluted and resultant emulsion was...

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Bibliographic Details
Published in:European journal of pharmaceutical sciences 2008-10, Vol.35 (3), p.183-192
Main Authors: Dixit, R.P., Nagarsenker, M.S.
Format: Article
Language:English
Subjects:
Animals
Anticholesteremic Agents - chemistry
Anticholesteremic Agents - pharmacokinetics
Anticholesteremic Agents - pharmacology
Azetidines - chemistry
Azetidines - pharmacokinetics
Azetidines - pharmacology
Biological Availability
Calorimetry, Differential Scanning
Capsules
Chemistry, Pharmaceutical
Cholesterol - blood
Colloidal silicon dioxide
Crystallography, X-Ray
Disease Models, Animal
Emulsions
Ezetimibe
Hydrogen-Ion Concentration
Hypercholesterolemia - blood
Hypercholesterolemia - drug therapy
Hyperlipidemia
Male
Microscopy, Electron, Scanning
Nanoparticles
Oils - chemistry
Rats
Rats, Sprague-Dawley
Self-nanoemulsifying granules
Silicon Dioxide - chemistry
Solubility
Surface-Active Agents - chemistry
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Summary:Self-nanoemulsifying granules (SNGs) were formulated with the objective of enhancing the bioavailability of the ezetimibe. Various modified oils, surfactant and cosurfactant mixtures were used and composition of self-nanoemulsifying system (SNS) was optimized. SNS diluted and resultant emulsion was characterized for mean globule size and stability. The self-nanoemulsifying systems were formulated into free flowing self-nanoemulsifying granules using varying proportions of hydrophilic colloidal silicon dioxide as an adsorbing agent. Self-nanoemulsifying granules were characterized by X-ray diffraction pattern, differential scanning calorimetry, dissolution profile and for in vivo performance in rats. X-ray diffraction studies indicated loss of crystallinity and/or solubilisation of ezetimibe in the self-nanoemulsifying granules. It was supported by SEM studies, which did not show evidence of precipitation of the drug on the surface of the carrier. Dissolution studies revealed remarkable increase in dissolution of the drug as compared to plain drug. In vivo evaluation in rats showed significant decrease in the total cholesterol levels as compared to positive control. The SNGs filled into hard gelatin capsules showed two to threefold increase in the dissolution rate as compared to plain drug filled capsules signifying its potential in improved delivery of lipophilic drugs.
ISSN:0928-0987
1879-0720
DOI:10.1016/j.ejps.2008.06.013