Study On Ergoloid Mesylate Sustained-release Tablets

Mesylate Dihydroergotaxine is effective in treatment for degenerative brain cerebral as cerebral metabolism, which is the only US FDA-approved treatment of cerebra, peripheral vascular disease treatment drugs. Mesylate Dihydroergotoxine mainly contains three kinds of alkaloids:Mesylate Dihydroergocomine, Mesylate Dihydroergocristine, Mesylate Dihydroergotoxine α β isomer, with the ration of 3:3:2:1.This product can directly act on the central nervous system, dopamine and serotonin receptors and enhance release of neurotransmitters from presynaptic nerve terminals and simulation of postsynaptic receptor. It can also improve neurotransmitter function and block a-receptor to relieve spasm and reduce vascular resistance thus increasing the blood supply to the brain tissue and oxygen utilization. Oral and intravenous formulations are used commonly in the clinic. Intravenous is a little trouble. Oral tablets mainly conclude tablets and capsules. The low bioavailability of ordinary tablets will quickly increase blood concentration, which will cause adverse reactions. However, the sustained-release formulation can maintain a stable blood level, avoiding adverse reactions by the rapid increase of the plasma concentrations. So it is necessary to imitate for reducing cost and meeting the needs of patients. The main research as follow:1.The prescription and technology research of Mesylate DihydroergotoxineObjective:To prepare ergoloid mesylate sustained-release tablets, and to study the in vitro release mechanism. Methods:The ergoloid mesylate sustained-release tablets were prepared with HPMC as sustained release matrix. Orthogonal test was performed to optimize the formulation with in vitro accumulative drug release rate as index and the amount of HPMC, lactose, dibasic calcium phosphate and tartaric acid as factors. The release mechanism of optimized formulation was investigated. Results:Ergoloid mesylate sustained-release tablets were prepared with wet granulation using HPMC (K4M) as gel-matrix materials, lactose and dibasic calcium phosphate as filler, tartaric acid as a pH adjusting agent. The drug can be sustainably released over 12h in vitro. The accumulative dissolution rate reached 97.1% with in 12h, and its release behavior imitated as the Higuchi equation. Conclusion:This formula is reasonable. The preparation procedure is stable and feasible. The production cost is significantly reduced2.Quality standards on Mesylate DihydroergotoxineObjective:In order to control the quality of DHETM sustained-release tablets. Method:To establish a reliable HPLC assaying method, dissolution methodand stability analysis method. Result:The method is accurate, sensitive, the adjuvant and degradation product don’t interfere principal agent was established. Conclusion:Establish gliclazide quality criteria for preparation production and go on sale.3.The research of DHETM’s stabilityObjective:Inspect the stability study for the DHETM sustained-release tablets. Method:Inspect the stress test, and the accelerated test and the long-term stability of the test of DHETM. Result:the stress test has showed that DHETM sustained-release tablets, which are prepared according to the optimal formulation and technology, are stable under high temperature, high humidity and intensive light.Conclusion:The preparation proved a good stability which will provide the basis for packaging materials selection, storage conditions and the formulation of the deadline.