[Optimization and evaluation of a new antischistosomal drug QH917 self-microemulsifying drug delivery system].
To screen a new poorly water-soluble antischistosomal drug QH917 self-microemulsifying drug delivery system which has steady release in vitro and absorption in situ separately. The formulation was optimized using central composite design-response surface methodology. Independent variables were oil content (%) and the weight ratio of surfactant and cosurfactant (Km), while response variables were self-microemulsifying time (t), mean particle size (PS) and polydispersity index (PI). The effects of ionic strength, food, pH, rotation speed and medium volume on drug release of the optimized formulation were evaluated under conditions simulating in vivo physiological situations. The absorption of the optimized formulation was studied using in situ intestinal permeability technique of rats. The optimized formulation was as follows: the content of media chain triglyceride (MCT) was 30%-34% (w/w); and the weight ratio of surfactant polyoxyl 40 hydrogenated castor oil (Cremophor RH40) and co-surfactant ethanol was 4.8-5.2. Release of QH917 from the optimized formulation was nearly unaffected by ionic strength, food, pH, rotation speed and medium volume. There was no marked difference of the absorption rate between rats with and without ligated bile duct in rat intestinal permeability technique. Inter-individual variability in absorption of the optimized formulation was negligible. Central composite design-response surface methodology is an efficient approach for optimizing formulations of self-microemulsifying drug delivery system; drug release in vitro and absorption behavior in situ of the optimized formulation is steady.
Zhang
Jian-yuan
JY
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Gan
Yong
Y
Gan
Li
L
Zhu
Chun-liu
CL
Pan
Wei-san
WS
D000818:Animals; D037621:Artemisinins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions; D007408:Intestinal Absorption; D008297:Male; D010316:Particle Size; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012556:Schistosomicides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D014280:Triglycerides / Q000737:chemistry
D037621:Artemisinins; D004655:Emulsions; D012556:Schistosomicides; D013501:Surface-Active Agents; D014280:Triglycerides