Research And Evaluation Of Huperzine A Oral Sustained - Release Preparations

Huperzine—A(HA) has been used long time for Aizheimer’s disease(AD), enhance the the faculty of study, improve the conditions of memory。Since 1994 years, Huperzine-A has the qualification from Ministry of health to be the new drug in order to cure AD, and it has many relative cases of a particular disease to prove absolutely the Huperzine A has the curative effect to AD。Clinically, little of patients has the side affect such as tinnitus、dizziness and slabber, and minority people’s compliance is bad。In the domestic market, Huperzine A has a lot of dosage form such as injection, tablets and capsule and so on。Fewer adverse reactions and better patient-compliance would be expected if we develop Huperzine A into oral sustained/controlled release system.Aims:Three new oral dosage forms of Huperzine A will be prepared by modern drug delivery technology(Huperzine A matrix tablets, expandable tablets and floating tablets), be compared and evaluated by in vitro test, and one of them will be choosed to be the most preferred dosage form for Huperzine A. We hope to build foundation for new oral drug delivery systems (DDS) development of Huperzine A and to offer reference for similar research。Methods:The in vitro drug commulative release is the most important aspect to evaluated drug release.1 Methods for sample assay and drug release test in vitro were established。2 Viscosity、swelling and erosion properties of hydrophilic polymer commonly used were tested as the basis for formulation and process design。3 The formulations and process of three dosage forms were studied by single-factors test and optimized by orthogonal or uniform design。4 Drug release profiles in vitro, key influencing factors and release mechanism of three preparations were studied。Results:1 RP-HPLC methodology for analysis of Huperzine A samples was established with appropriate convenience and accuracy。The cup method in Chinese Pharmacopoeia(Edition 2005)was adopted for in vitro release test of huperzine A preparations.2 Huperzine-A its solubility and oil/water distribution factor changed markedly in solvents with different PH and osmotic pressure. On the one hand, the solubility is decline with the Ph value; on the other hand, the oil/water distribution factor is increase with the Ph。Polymers with different units and polymerization degree different in viscosity, swelling and erosion properties in water.3 Huperzine-A hydrogel matrix release tablets with HPMC as matrix material showed excellent zero order release profile in vitro (2-10h, r=0.9945, F12>90%), and the drug profile can hardly influencing and drug release mechanism based on diffusion and erosion4 Huperzine-A expandable tablets composed of PEO released drug completely with swelling rate of 1.789time/h, showed markedly sustained-release characteristics with the mechanism of diffusion and erosion and to be in line with the Higuchi order。Its expandable property was based on the PEO and expandable agents。In order to improve the floating ability, we can relied on some effervescing agents。5 Huperzine-A expandable tablets composed of HPMC showed markedly sustained-release characteristics with the mechanism of diffusion and erosion。Its expandable property was based on the HPMC and effervescing agents as "hydrodynamically balanced systems"。Conclusion:Taken together, the results suggest that the three kinds-of sustained-release tablets is acceptable dosage form for oral sustained/controlled delivery of Huperzine A, in which its formulation and process being convenient, drug release in vitro being more complete。Innovations:1.Swelling and erosion properties of common hydrophilic polymers in water were compared initially。2.hydrogel matrix controlled-release tablets, expandable tablets and floating tablets of Huperzine A were prepared, their drug release mechanism in vitro were discussed。3.We can optimizing the best Gastro retentive drug delivery system dosage form for research and development of oral products for Huperzine A。...