Studies On Total Alkaloid Of Rhizoma Corydalis Decumbentis Drug-resin Controlled Release Microcapsule

In this paper, drug resin sustained-release delivery system was prepared with Rhizoma Corydalis Decumbentis included in 2005 edtion,first partment,Pharmacopoeia of People’s republic of China as model drug and a new type of excipient-strong acid cation exchange resin as drug carrier.By Protopine and Tetrahydropalmatine as indexity component,systematic studies were made on decumbent corydalis tuber total alkaloids(TA) sustained-release microcapsule based on ion exchange resin.The studies were as follows:1) Acid dye colorimetry was established for detecting the Determination of TA content. Immersion method was use to extract TA and macroporous absorbent resin D101 was used to purification TA. The Determination of TA content can be obtained at 78±2%.2) High performance liquid chromatography was established for content of drug loading,drug release tests,assaying tests and determination of plasma drug concentration in rats,which was proved sensitive and reliable.3)The drug-resin complexes(DRC) were prepared by batch method.The key factors influencing on the rate and equilibrium of Protopine and Tetrahydropalmatine with ion exchanger eaction were investigated,and Protopine and Tetrahydropalmatine kinetics were studied.Considering the equilibrium time and the amounts of drug-loading, as well as convenient facility,the batch method was selected for preparing DRC at 323K with intial drug concentration which could achieve at saturated exchange capacity of resin.The combination mechnisim of TA-resin was investigated by DSC,witch ascertained that the combination force beween TA and resin was ionic bond interaction instead of physical adsorption interaction.4)The studies of the drug release in vitro showed that the rate and amounts of Protopine and Tetrahydropalmatine release was increased with rising ion concentration and pH values of the release media. The factors affecting Protopine and Tetrahydropalmatine release from DRC were explored by similar factor. Consequently the drug release experiment was carrieded out using 900ml 0.15mol·L-1NaCl (pH6.8) solution as release medium in vitro with 50rpm rotate speed at 37℃.The mechnism of release in vitro showed that the diffusion of Protopine and Tetrahydropalmatine from the resin partieles was controlled by particle diffusion process according to Viswanathan.5)The drug resin microcapsules were prepared with ethyl cellulose by the method of intra-liquid desication.Based on the results of single factor tests,the optimum coating formula was acquired by orthogonal design method.The optimal microcapsules were able to maintain a sustained release in vitro.The repeatability of three batches was good.Through investigating the Protopine and Tetrahydropalmatine release from the microcapsules followed first order kineties,belonging to Fiek’diffusion.6)The behaviors in vivo of TA resin sustained-release capsules and the refereneecrude TA were evaluated in rats and the Pharmacokineties Parameters were caleulated by DAS2.0. The results showed that the self-made sustained-release capsules had an obvious sustained release effect...