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, AUC_0∼t and C_max 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. 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.

Keywords::

• Carbamazepine
• S-SMEDDS
• relative bioavailability
• precipitation inhibitor

Acknowledgements

We would like to express our gratitude to Prof. R. Jinxiu R and Z. Zhenqing for consultation in plasma concentration testing.

Declaration of interest

This work was supported by the National Medical foundation of PLA in China. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.