[Preparation and evaluation of self-microemulsifying drug delivery systems containing atorvastatin].
OBJECTIVE
To prepare self-microemulsifying drug delivery system (SMEDDS) containing atorvastatin,and decrease its size to improve the solubility in the stomach. And to study the effect of the resultant microemulsion in reducing the presystemic clearance in the gastrointestinal mucosa and hepatic first-pass metabolism, improving the oral bioavailability, and reducing side effect and expenditure.


METHODS
Pseudoternary phase diagrams were used to evaluate the self-microemulsification existence area. The HPLC analyses in vitro and in vivo were set up. Solubility in various vehicles was determined. The self-microemulsification efficiency was assessed, such as self-microemulsification time, stability, particle size and zeta potential. SMEDDS containing atorvastatin, non-ionic surfactant and lipid were prepared. Droplet size/distributions and zeta potential of the resultant microemulsion were determined. Photos were taken with transmission electron microscope. Oral bioavailability was studied on prepared SMEDDS hard capsules and compared with that of the conventional tablet in Beagle dogs in vivo.


RESULTS
The optimal formulations had wide microemulsion existent field and had good self-microemulsifying efficiency. Droplet size was within 100 nm and showed Gaussian distribution. After oral administration of SMEDDS capsules and the conventional tablet to fasted Beagle dogs, the Cmax from SMEDDS was greater than that of the conventional tablet. AUC from zero to 24 h of SMEDDS was about 1.5-fold higher than that of the conventional tablet. Oral bioavailability of atorvastatin SMEDDS was greater than that of the conventional tablet.


CONCLUSIONS
The results indicated the potential use of SMEDDS for the delivery of atorvastatin to increase its oral bioavailability.
Research Division of Clinical Pharmacy, Huashan Hospital, Fudan University, Shanghai 200040, China. hairong_shen@163.com
Hai-rong
HR
Shen
Zhong-dong
ZD
Li
Ming-kang
MK
Zhong
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D000069059:Atorvastatin; D001682:Biological Availability; D004285:Dogs; D016503:Drug Delivery Systems; D004655:Emulsions; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011758:Pyrroles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012995:Solubility
D004655:Emulsions; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; C022131:cremophor; D011092:Polyethylene Glycols; C000515:cremophor EL; D000069059:Atorvastatin; D005990:Glycerol