Hydrophilic Matrix Sustained Release Tablets Of Oleanolic Acid Based On Cyclodextrin Complex

Objective:To reduce the frequency of oral administration, hydrophilic gel matrix sustained release tablets of oleanolic acid(OA) based on its cyclodextrin inclusion complex were prepared. OA has a low water solubility. To improve its water solubility and thereafter fulfill a satisfactory drug release profile of the sustained release tablets,the inclusion complex of OA with β-Cyclodextrin (β-CD) was prepared. And the effects of salt formation of OA and the addition of polyvinylpyrrolidone (PVP), one of the water-soluble polymers, on the complexation efficiency and drug solubility were investigated. Then the formulation of hydrophilic matrix sustained release tablets of oleanolic acid based on cyclodextrin complex were optimized.Methods:The inclusion complexes were prepared by saturated water solution method. Aqueous solubility of OA was determined using HPLC. Infrared spectroscopy was used to validate the inclusion complexes and preliminarily reveal the effect mechanism of PVP. Hydrophilic matrix sustained release tablets of OA were further prepared by using using hydroxypropyl methyl cellulose (HPMC) as the matrix material, lactose and microcrystalline cellulose as the filling agents, and magnesium stearate as lubricant, The factors which might influence on drug release of the sustained-release tablets of OA were investigated to optimize the formulation.Results:The water solubility of OA had 3.4-times increase after inclusion with β-CD. The complexation efficiency improved and the drug solubility was further increased to 107-fold by salt formation of OA. However, the water solubility of OA reduced with the addition of high concentration of PVP solution during the inclusion process. Infrared spectrum analysis indicated that the inclusion complex of OA and β-CD was formed and there was strong molecular interaction between OA and PVP or OA and β-CD. The optimal formulation of OA hydrophilic matrix sustained release tablets was listed as following:OA 10%(inclusion complex, about 50% of the total weight), HPMC K4M 25%, lactose 25%. The obtained tablets showed a good extended-release effect.Conclusion:The obtained sustained tablets of OA in this study was characterized by simple manufacture technology, low cost and good extended-release effect.