Studies on preparation of carbamazepine (CBZ) supersaturatable self-microemulsifying (S-SMEDDS) formulation and relative bioavailability in beagle dogs

Abstract

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, AUC0∼t and Cmax were 9.83 ± 2.47 μg·ml−1·h and 4.96 ± 1.16 μg·ml−1, compared to the conventional tablet which were 1.67 ± 1.19 μg·ml−1·h and 0.74 ± 0.19 μg·ml−1, respectively. AUC0-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, AUC0–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.