Evaluation of Carbamazepine (CBZ) Supersaturatable Self-Microemulsifying (S-SMEDDS) Formulation In-vitro and In-vivo.

Abstract

The supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) represents a new thermodynamically stable formulation approach wherein it is designed to contain a reduced amount of surfactant and a water-soluble polymer (precipitation inhibitor or supersaturated promoter) to prevent precipitation of the drug by generating and maintaining a supersaturated state in-vivo. The supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) of CBZ was evaluated in-vitro and in-vivo. Three different formulations of CBZ were prepared and drug precipitation behavior, dissolution rate in-vitro and particle size distribution were evaluated. Studies on CaCO-2 permeability of three formulations were also carried out. Pharmacokinetic studies were conducted in beagle dogs with administration dose of 200mg to assess bioavailability in-vivo compared with commercial tablet. The results showed that the presence of a small amount of polymeric precipitation inhibitor (PVP) effectively sustained supersaturated state by retarding precipitation kinetics. The mean particle size after dispersion was about 33.7 nm and the release rate from S-SMEDDS was significantly higher than the commercial tablet in-vitro. S-SMEDDS formulation with precipitation inhibitor decreased impairment to cells due to a lower surfactant level compared to SMEDDS. The absorption of S-SMEDDS in-vivo resulted in about 5-fold increase in bioavailability compared with the commercial tablet and the reproducibility of plasma concentration profiles intra-individual was improved remarkably. This study demonstrates that S-SMEDDS technology provide an effective approach for improving the extent of absorption of poorly-soluble drugs with low level of surfactant.