Formulation and biopharmaceutical evaluation of silymarin using SMEDDS.
Silymarin has been used to treat hepatobiliary diseases. However, it has a low bioavailability after being administered orally on account of its low solubility in water. In order to improve the dissolution rate, silymarin was formulated in the form of a self-microemulsifying drug delivery system (SMEDDS). The optimum formulation of SMEDDS containing silymarin was obtained based on the study of pseudo-ternary phase diagram. The SMEDDS consisted of 15% silymarin, 10% glyceryl monooleate as the oil phase, a mixture of polysorbate 20 and HCO-50 (1:1) as the surfactant, Transcutol as the cosurfactant with a surfactant/cosurfactant ratio of 1. The mean droplet size of the oil phase in the microemulsion formed from the SMEDDS was 67 nm. The % release of silybin from the SMEDDS after 6 hours was 2.5 times higher than that from the reference capsule. After its oral administration to rats, the bioavailability of the drug from the SMEDDS was 3.6 times higher than the reference capsule.
Woo
Jong Soo
JS
Pharmaceutical Research Lab. Hanmi Pharm. Co., Hwaseong 445-913, Korea.
Kim
Tae-Seo
TS
Park
Jae-Hyun
JH
Chi
Sang-Cheol
SC
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002214:Capsules; D002368:Castor Oil / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004655:Emulsions; D005026:Ethylene Glycols / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D005989:Glycerides / Q000737:chemistry; D008297:Male; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013997:Time Factors; D014867:Water / Q000737:chemistry
D000975:Antioxidants; D002214:Capsules; D004655:Emulsions; D005026:Ethylene Glycols; D005079:Excipients; D005989:Glycerides; D009821:Oils; D011136:Polysorbates; D012838:Silymarin; D013501:Surface-Active Agents; D014867:Water; D000077385:Silybin; C023040:polyethoxylated castor oil; D002368:Castor Oil; C010111:carbitol; C005953:monoolein