Studies On The OAHPDS Microspheres And Synthesis Of HPMCAS

In this paper, oleanolic acid phthalate disodium (OAHPDS) was selected as the model drug. And the matrix type microspheres, OAHPDS-HPMCAS microspheres, and OAHPDS-Hydroxyapatite microspheres (OAHPDS-HAPm) coated with Eudragit RS were prepared. The physicochemical and in vitro release properties of the microspheres were investigated in order to evaluate the potential applications of HPMCAS and HAPm in the oral delivery of small molecular drugs. The synthesis and physicochemical properties of HPMAS were also investigated.OAHPDS were synthesized via the esterification of oleanolic acid and phthalic anhydride, the resulted product was characterized by TLC, HPLC, UV, FTIR,1H-NMR and mass spectra, and its physicochemical properties were also investigated. As the OAHPDS is relatively unstable in acidic environment, an enteric dosage form is perfered for oral delivery of OAHPDS.OAHPDS-HPMCAS microspheres were prepared by emulsion-solvent evaporation method. The microspheres were characterized by various techniques and the in vitro drug release experiments were performed to evaluate its enteric dissolving behavior. The FT-IT measurements revealed the inter-molecular hydrogen bonds between the drug and polymer. The drug release results showed that the solid state of drug in the microspheres and the morphology of the microspheres would influence the release of drug in acidic medium. It is presumed that the drug molecules in the microspheres played a role of "plasticizer", which would insert between the glucose chains of HPMCAS and promoted the immigration of glucose chains. The results evidenced that HPMCAS may be a ideal carrier material for the delayed release of drugs in the small intestine.OAHPDS was loaded on HAPm by soaking the HAPm in drug solution. The adsorption/desorption properties of OAHPDS to HAPm were studied to verify the the mechanism of adsorption and desorption. OAHPDS loaded HAPm was coated with Eudragit RS by drying in liquid method. The influences of medium volume, pH value, ionic strength and types of buffer solutions on the in vitro release properties of coated microspheres were studied. The results showed that zero-order release profiles of coated microspheres can be obtained, which suggested the potential application of HAPm as the carrier material for oral administration of small molecular drugs.Finally, HPMCAS was synthetized and its preliminary physicochemical properties were evaluated. Compared with the commercially available HPMCAS (AS-LF), The physicochemical properties and the release behaviors of microsphere prepared with synthesized HPMCAS were similar to that of the commercially available HPMCAS (AS-LF).