Dry adsorbed emulsion of simvastatin: optimization and in vivo advantage.
In the present study, Simvastatin was incorporated in emulsion of soybean oil and propylene glycol monocaprylate as oily phase and Tween 80 and Cremophor EL as surfactants and also their mixtures. Dry adsorbed emulsions were prepared by using colloidal silicon dioxide in varying proportions to adsorb the liquid emulsion. Liquid emulsions were characterized for viscosity and mean globule size, and the dry adsorbed emulsions were evaluated for powder characteristics and reconstitution properties, dissolution profile, and for in vivo efficacy in rats. DSC and X-ray diffraction studies indicated complete amorphization and/or solubilization of Simvastatin in the dry adsorbed emulsion. 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 compared to plain drug. One of the optimized formulations provided 10-fold enhancement in the dissolution compared to drug powder. After 24 hr of induction of hyperlipidemia in rats using poloxamer F127, administration of dry adsorbed emulsions effected significant reduction in the total cholesterol with levels of 439 mg/dL compared to 585 mg/dL of drug treated group (p < 0.01). Significant increase in the high-density lipoprotein levels were also observed after 4 days of treatment compare to positive control (p < 0.01).
Dixit
Rahul P
RP
Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (East), Mumbai, India.
Nagarsenker
Mangal S
MS
D000179:Acrylates / Q000737:chemistry; D000327:Adsorption; D000818:Animals; D000924:Anticholesteremic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002784:Cholesterol / Q000097:blood; D004655:Emulsions; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D008075:Lipoproteins, HDL / Q000097:blood; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D012212:Rheology; D012822:Silicon Dioxide / Q000737:chemistry*; D019821:Simvastatin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D012995:Solubility; D013024:Soybean Oil / Q000737:chemistry; D014783:Viscosity; D014961:X-Ray Diffraction
D000179:Acrylates; D000924:Anticholesteremic Agents; D004655:Emulsions; D008075:Lipoproteins, HDL; D011136:Polysorbates; D011208:Powders; C000515:cremophor EL; D012822:Silicon Dioxide; D013024:Soybean Oil; D002784:Cholesterol; D019821:Simvastatin; C030214:propylene glycol monoacrylate; D005990:Glycerol