Preparation and evaluation of self-microemulsifying drug delivery systems (SMEDDS) containing atorvastatin.
Atorvastatin is insoluble in aqueous solution and the bioavailability after oral administration is low. Self-microemulsifying drug delivery systems (SMEDDS) containing atorvastatin have been successfully prepared to improve its bioavailability. SMEDDS is a mixture of lipid, surfactant, and cosurfactant, which are emulsified in aqueous medium under gentle digestive motility in the gastrointestinal tract. Pseudo-ternary phase diagrams composed of various excipients were plotted. Droplet size, zeta-potential and long-term physical stability of the formulations were investigated. The release of atorvastatin from SMEDDS capsules was studied using the dialysis bag method in 0.1 M HCl and phosphate buffer (pH 7.4), compared with the release of atorvastatin from a conventional tablet. A pharmacokinetic study was performed in 6 beagle dogs after oral administration of 6 mg kg-1 atorvastatin. The bioavailability of atorvastatin SMEDDS capsules was significantly increased compared with that of the conventional tablet. SMEDDS capsules consisting of Labrafil, propylene glycol and Cremophor RH40 provided the greatest bioavailability. Our studies indicate that the use of SMEDDS for the delivery of atorvastatin can improve its bioavailability.
Shen
HaiRong
H
Department of Pharmacy, Huashan Hospital, Fudan University, 12 Wulumuqi M. Road, Shanghai, 200040, China. hairong_shen@163.com
Zhong
MingKang
M
D000284:Administration, Oral; D000818:Animals; D000069059:Atorvastatin; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D005989:Glycerides / Q000737:chemistry; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D046529:Microscopy, Electron, Transmission; D016011:Normal Distribution; D010316:Particle Size; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry; D011758:Pyrroles / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013607:Tablets
D004655:Emulsions; D005079:Excipients; D005989:Glycerides; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D013501:Surface-Active Agents; D013607:Tablets; C022131:cremophor; D011092:Polyethylene Glycols; D019946:Propylene Glycol; D000069059:Atorvastatin