Formulation and in vivo evaluation of self-nanoemulsifying granules for oral delivery of a combination of ezetimibe and simvastatin.
Self-nanoemulsifying granules were formulated with the objective of improving the bioavailability of the ezetimibe and simvastatin when administered together. Composition of self-nanoemulsifying system (SNS) was optimized using various modified oils, surfactant, and cosurfactant mixtures. SNSs were mixed with water and resultant emulsions were characterized for mean globule size and stability. SNSs were adsorbed on hydrophilic colloidal silicon dioxide to give free-flowing self-nanoemulsifying granules. Self-nanoemulsifying granules were characterized by X-ray diffraction pattern, scanning electron microscopy, dissolution profile, and for in vivo performance in hypercholesterolemic rats. X-ray diffraction studies and scanning electron microscopy indicated loss of crystallinity and/or solubilization of both drugs in the self-nanoemulsifying granules. Self-nanoemulsifying granules effected substantial increase in dissolution of the drugs as compared with pure powder of drugs. In vivo evaluation in rats showed significant decrease in the total cholesterol levels and triglyceride levels in rats as compared with positive control confirming potential of self-nanoemulsifying granules as a drug delivery system for the poorly water-soluble drugs.
Dixit
Rahul P
RP
Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (East), Mumbai, India.
Nagarsenker
M S
MS
D000284:Administration, Oral; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001384:Azetidines / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000097:blood; D004655:Emulsions; D000069438:Ezetimibe; D008297:Male; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D014961:X-Ray Diffraction
D000924:Anticholesteremic Agents; D001384:Azetidines; D004655:Emulsions; D002784:Cholesterol; D019821:Simvastatin; D000069438:Ezetimibe