The Research Of Simvastatin Self-Microemulsifying Capsules

Simvastatin self-microemulsifying capsules, choosing simvastatin as the model drug, was thermodynamically stable oil-in-water self-microemulsifying capsules. Simvastatin (SV) is a highly effective cholesterol-lowering agent, which is widely used in the treatment of hypercholesterolemia. Most oral dosage forms of simvastatin had low bioavailability because simvastatin could hardly dissolve. Therefore, self-microemulsifying drug delivery system (SMEDDS) was selected as the carrier to prepare Simvastatin self-microemulsifying capsules to increase dissolution, advance absorption and enhance bioavailability of simvastatin.In this research, an HPLC method was developed for assay of SV and in vitro release of SV self-microemulsifying capsules. Stability of SV had been rudimentarily investigated. The results showed that SV exposed to air and exposed to 60 ℃ were unstable, and SV would suck up moisture when it was exposed to high humidity.To identify the SMEDDS region, pseudo-ternary phase diagrams were constructed to investigate the effects of oils, cosurfactants, mass ratio of TPGS to cosurfactants, additives on SV self-microemulsifying capsules. Orthogonal experiment based on main influencing factors was carried out by taking area of microemulsion region in the diagram as main evaluating indexes. And the optimum formulation and preparation process of SV SMEDDS were established. The in vitro release behavior of SV self-microemulsifying capsules was rudimenarily investigated by bulk-equilibrium reverse dialysis bag technique.Physico-chemical properties of SV self-microemulsifying capsules were investigated. The result showed that interfacial tensions was 36.04×l0^-3N·m^-1, phase inversion temperature was 85℃, mean particle size was 23.8±4.2 nm. After storing 3 month at 4℃, 25℃ and 60℃, the content of SV, appearance, the time of self-microemulsifying and mean particle size of SV self-microemulsifying capsules were studied and the results proved that SV self-microemulsifying capsules was very stable thermodynamically.Finally, the in vivo pharmacokinetics behavior of SV self-microemulsifying capsules in...