Evaluation on a supersaturatable self-microemulsifying (s-smdds) formulation of biphenyl dimethyl dicarboxylate (BDD) in Vitro and in Vivo

Abstract

To enhance the dissolution and oral bioavailability of poorly water-soluble biphenyl dimethyl dicarboxylate (BDD), the supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) was developed by adding a water-soluble polymer PVP to prevent precipitation of the drug and maintain a supersaturate state in vivo. Ternary phase diagrams were drawn to evaluate the microemulsification domain. The formulations were characterized by testing the physical stability of the drug, particle size and zeta potential. The pharmacokinetic study in beagle dogs was performed for the S-SMEDDS, SMEDDS formulation and the market drop pills. The optimized S-SMEDDS formulation consist of 35% (w/w) Cremphor EL35, 33% (w/w) Transcutol HP, 30% (w/w) MCT and 2% (w/w) PVPK30 of each excipient showed minimum mean droplet size (37.71 ± 0.87nm) and optimal drug release profile and better physical stability in water compared with the PVP absent SMEDDS. The in vivo studies showed that S-SMEDDS had significantly increased the C_max and area under the plasma concentration-time curve (AUC) (P < 0.01). The S-SMEDDS formulation should be an effective oral dosage form for improving oral bioavailability of water-insoluble BDD.

Keywords:
biphenyl dimethyl dicarboxylate; supersaturatable self-microemulsification; water-soluble polymer; accumulated dissolution; bioavailability