evaluation of carbamazepine (cbz) supersaturatable self-microemulsifying (s-smedds) formulation in-vitro and in-vivo

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.