Studies on preparation of carbamazepine (CBZ) supersaturatable self-microemulsifying (S-SMEDDS) formulation and relative bioavailability in beagle dogs.
The main purpose of this work was to develop a supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) of carbamazepine (CBZ). S-SMEDDS of CBZ was prepared and drug precipitation behavior, dissolution rate in vitro and particle size distribution were evaluated. The relative bioavailability of S-SMEDDS formulation of CBZ was evaluated in beagle dogs compared with a commercial tablet. The results showed that the presence of a small amount of polymeric precipitation inhibitor (PVP) effectively sustained the supersaturated state by retarding precipitation kinetics. The mean particle size of S-SMEDDS formulation after dispersion was about 33.7?nm and the release rate from S-SMEDDS was significantly higher than the commercial tablet in vitro. In pharmacokinetic parameters of S-SMEDDS formulation, AUC(0?t) and C(max) were 9.83???2.47??g?ml(?1)?h and 4.96???1.16??g?ml(?1), compared to the conventional tablet which were 1.67???1.19??g?ml(?1)?h and 0.74???0.19??g?ml(?1), respectively. AUC(0-t) of S-SMEDDS increased nearly five times compared to the market tablet with the same administration dose of 200?mg. On the other hand, AUC(0?t) of S-SMEDDS with a dose of 50?mg was about 85.9% compared to the commercial tablet with a dose of 200?mg. Thus, it was concluded that S-SMEDDS provide an effective approach for improving the extent of absorption of CBZ with a low surfactant level.
Zhang
Nan
N
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
Zhang
Weidong
W
Jin
Yinghua
Y
Quan
Dong-qin
DQ
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002220:Carbamazepine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods*; D045703:Emulsifying Agents; D004655:Emulsions; D008297:Male; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013607:Tablets
D045703:Emulsifying Agents; D004655:Emulsions; D009821:Oils; D013501:Surface-Active Agents; D013607:Tablets; D002220:Carbamazepine