The Exploration For Improving The In Vitro Dissolution Rate Of Ginsenoside Rg₃ And Developing Its Osmotic Pump

ObjectiveThe purpose of this experiment is to develop osmotic pump tablets of Ginsenosides Rg3. The solid dispersion of Ginsenosides Rg3 was firstly prepared. We optimized the Ginsenoside Rg3 prescription using single factor method and developed the Elementary osmotic pump tablets(EOP) and push-pull osmotic pump tablets(PPOP). Sability investigation of the prepared osmotic pump tablets was made. Mesoporous silica nanoparticles(MSN) technology was used to improve the solubility and the in vitro dissolution rate of Ginsenosides Rg3.MethodsIn this study, the solid dispersion of Ginsenosides Rg3 was prepared. We chose three kinds of polymer carriers(polyethylene glycol(PEG 6000), povidone(PVP K30), Poloxamer 188(F68)) as the carriers and studied their impact on the ginsenosides Rg3 solubility and dissolution rate. We investigated several factors such as the kind and amount of osmotic active substances, the amount of suspending agent, the amount of porogen and the coating thickness of osmotic pump tablets using single factor method to optimize the Ginsenoside Rg3 prescription. We developed the Elementary osmotic pump tablets(EOP) and push-pull osmotic pump tablets(PPOP) to compare their influence on the osmotic pump tablets release behavior. A novel technology, mesoporous silica nanoparticles(MSN), was used to improve the solubility and the in vitro dissolution rate of Ginsenosides Rg3, which is firstly loaded into the mesoporous of MSN using solvent evaporation method with 1,1,1,3,3,3- Hexafluoro-2-propanol(HFIP) as the solvent. Then we examined the influence of the ratio of Ginsenoside Rg3 and MSN on the dissolution rate and characterized Ginsenoside Rg3. MSN and Rg3-MSN were characterized using transmission electron microscopy(TEM), scanning electron microscopy(SEM), differential scanning calorimetry(DSC), X-ray diffraction method(XRD) and Fourier transform infrared spectroscopy(FT-IR) technology.ResultsThe results showed that it could improve the solubility and the in vitro dissolution rate significantly at the ratio of 1:10 of Ginsenosides Rg3 and F68. So F68 was selected as the carrier and the ratio of drug and carrier was 1:10. Comparing PPOP with EOP, PPOP released rapidly and completely than EOP in 24 h. The structure characterization showed that MSN could effectively inhibit the crystallization of Ginsenoside Rg3 and made it stored in the mesoporous at amorphous form, so that MSN could improve Ginsenoside Rg3 in vitro dissolution rate significantly. Moreover the higher proportion of MSN, the rapider dissolution rate.ConclusionThe osmotic pump tablets of Ginsenosides Rg3 developing in this study had a faster release rate. The drug released rapidly and completely within 24 h to avoid wasting the drug. The osmotic pump tablets of Ginsenosides Rg3 achieved the desired controlled-release effect to improve bioavailability. The release uniformity of homemade osmotic pump tablets was good, and the appearance and related substances examination conformed to the requirements of pharmacopoeia. Mesoporous silica nanoparticles can significantly improve the dissolution rate of Ginsenosides Rg3 to solve the problem of low solubility. This provided effective reference for improvement of the hydrophilicity of poorly water-soluble drugs.