Development of silymarin self-microemulsifying drug delivery system with enhanced oral bioavailability.
The objective of this work was to develop a self-microemulsifying drug delivery system (SMEDDS) for improving oral absorption of poorly water-soluble drug, silymarin. The pseudo-ternary phase diagrams were constructed using ethyl linoleate, Cremophor EL, ethyl alcohol, and normal saline to identify the efficient self-microemulsification region. The particle size and its distribution of the resultant microemulsions were determined using dynamic light scattering. The optimal formulation with the best self-microemulsifying and solubilization ability consisted of 10% (w/w) of ethyl linoleate, 30% of Cremophor EL, and 60% of ethyl alcohol. The release of silymarin from SMEDDS was significantly faster than that from the commercial silymarin preparation hard capsule (Legalon). The bioavailability results indicated that the oral absorption of silymarin SMEDDS was enhanced about 2.2-fold compared with the hard capsule in fasted dogs. It could be concluded that SMEDDS would be a promising drug delivery system for poorly water-soluble drugs by the oral route.
Li
Xinru
X
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Yuan
Quan
Q
Huang
Yanqing
Y
Zhou
Yanxia
Y
Liu
Yan
Y
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004285:Dogs; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis*; D004339:Drug Compounding / Q000379:methods; D004655:Emulsions / Q000008:administration & dosage / Q000138:chemical synthesis*; D012838:Silymarin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D012995:Solubility
D000975:Antioxidants; D004337:Drug Carriers; D004655:Emulsions; D012838:Silymarin
Am J Health Syst Pharm. 1999 Jun 15;56(12):1195-7
10484652
Arzneimittelforschung. 1995 Jan;45(1):61-4
7893272
Eur J Drug Metab Pharmacokinet. 1990 Oct-Dec;15(4):333-8
2088770
Eur J Pharm Sci. 2002 Jun;15(5):405-15
12036717
Eur J Pharm Biopharm. 2006 Jul;63(3):288-94
16527467
J Pharm Sci. 2004 Jan;93(1):132-43
14648643
Eur J Pharm Sci. 2003 Sep;20(1):91-7
13678797
Eur J Pharm Sci. 2000 Oct;11 Suppl 2:S93-8
11033431
Int J Pharm. 2004 Apr 15;274(1-2):65-73
15072783
Int J Clin Pharmacol Ther Toxicol. 1992 Apr;30(4):134-8
1572758
Eur J Pharm Biopharm. 2000 Jul;50(1):179-88
10840200
Eur J Pharm Sci. 2005 Apr;24(5):477-86
15784337
Arzneimittelforschung. 1992 Jul;42(7):964-8
1329780
Eur J Pharm Sci. 2006 Jun;28(3):233-42
16650738
Yao Xue Xue Bao. 2004 Aug;39(8):631-4
15563067
Int J Pharm. 2007 Aug 1;340(1-2):84-91
17531411
Arch Pharm Res. 2007 Jan;30(1):82-9
17328246
Int J Pharm. 2001 Jan 16;212(2):233-46
11165081
Int J Pharm. 2006 Aug 17;319(1-2):162-8
16687221
Int J Pharm. 2002 Oct 10;246(1-2):75-83
12270610
Drug Dev Ind Pharm. 2000 May;26(5):523-9
10789064