Enhancement of oral bioavailability of the poorly water-soluble drug silybin by sodium cholate/phospholipid-mixed micelles.
OBJECTIVE
To evaluate a mixed micellar drug delivery system composed of sodium cholate and phospholipid for oral administration of silybin, a promising hepatoprotectants.


METHODS
The optimum formulation of sodium cholate/phospholipid-mixed micelles containing silybin was obtained based on the study of pseudo-ternary phase diagram. The dissolution of silybin-mixed micelles was investigated. The pharmacokinetic characteristics and bioavailability after oral administration of silybin-mixed micelles and silybin-N-methylglucamine were compared in dogs.


RESULTS
The mean particle size of prepared mixed micelles was 75.9+/-4.2 nm. The largest solubility of silybin was found to be 10.0+/-1.1 mg/mL in the optimum formulation of mixed micelles. The silybin-sodium cholate/phospholipid-mixed micelles showed a very slow release of silybin 17.5% (w/w) within 72 h in phosphate buffer (pH 7.4) and 15.6% (w/w) in HCl solution (pH 1.2). After oral administration to dogs, the relative bioavailability of mixed micelles versus silybin-N-methylglucamine in dogs was 252.0%.


CONCLUSIONS
Sodium cholate/phospholipid-mixed micelles are promising carriers in orally delivery of silybin, considering their capability of enhancing bioavailability and large-scale production.
Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang, China.
Jiang-nan
JN
Yu
Yuan
Y
Zhu
Li
L
Wang
Min
M
Peng
Shan-shan
SS
Tong
Xia
X
Cao
Hui
H
Qiu
Xi-ming
XM
Xu
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D004285:Dogs; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D008297:Male; D008823:Micelles; D010316:Particle Size; D010743:Phospholipids / Q000097:blood; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D020358:Sodium Cholate / Q000737:chemistry; D012995:Solubility
D000975:Antioxidants; D004337:Drug Carriers; D008823:Micelles; D010743:Phospholipids; D012838:Silymarin; D000077385:Silybin; D020358:Sodium Cholate