Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs.
The main purpose of this work is to prepare self-microemulsifying drug delivery system (SMEDDS) for oral bioavailability enhancement of a poorly water soluble drug, simvastatin. Solubility of simvastatin was determined in various vehicles. SMEDDS is mixture of oils, surfactants, and cosurfactants, which are emulsified in aqueous media under conditions of gentle agitation and digestive motility that would be encountered in the gastro-intestinal (GI) tract. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region and particle size distributions of the resultant microemulsions were determined using a laser diffraction sizer. Optimized formulations for in vitro dissolution and bioavailability assessment were Carpryol 90 (37%), Cremophor EL (28%), and Carbitol (28%). The release rate of simvastatin from SMEDDS was significantly higher than the conventional tablet. The prepared SMEDDS was compared with the conventional tablet (Zocor) by administering the prefilled hard capsules to fasted beagle dogs. The absorption of simvastatin acid from SMEDDS form resulted in about 1.5-fold increase in bioavailability compared with the conventional tablet. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as simvastatin by the oral route.
Kang
Bok Ki
BK
Department of Polymer Science and Engineering, Chonbuk National University, Duckjin Dong, Jeonju 561-756, South Korea.
Lee
Jin Soo
JS
Chon
Se Kang
SK
Jeong
Sang Young
SY
Yuk
Soon Hong
SH
Khang
Gilson
G
Lee
Hai Bang
HB
Cho
Sun Hang
SH
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D045703:Emulsifying Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D019821:Simvastatin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
D045703:Emulsifying Agents; D019821:Simvastatin