Study On Preparation Technology And Quality Control Of Danshenyin Sustained Release Pellets

ObjectiveDanshenyin was recorded in the Summary Verses of Post-classical Formulas,it composed by Salvia miltiorrhiza,Santalum album and Amomum villosum,and had the efficacy of promoting blood circulation to remove blood stasis and promoting qi circulation to relieve pain.Danshenyin was mainly used to treat the syndrome of qi stagnation and blood stasis.Currently,it is used to treat chronic gastritis,stomach and duodenal ulcer and coronary heart disease,angina pectoris,et al.It was observed that this prescription had significant therapeutic effect on patients with qi stagnation and blood stasis.Based on the research of early extraction process of the research group,the preparation technology of extracts from medicinal herbs was studied by the modern preparation technique to establish a feasible and stable preparation method,and ensure the safety,effectivity and quality control by formulating reasonable and feasible quality control scheme.Methods1.The researching of pharmaceutical technologyThe single factor method was used to select the species and usage amount of excipients and adhesives to determine the prescription composition;The process parameters of the preparation were optimized by L₄?4³?orthogonal experimental design;the types of pore-forming agents and anti-adhesives were investigated by single factor experiment with the coating material of Eudragit NE30D dispersion,and U₅?5³?uniform experimental design was carried out to optimize the usage amounts of the pore-forming agents and anti-adhesives and the added weight of the coating.Dissolution test in vitro was used to verify the coating process and the sustained release effect was observed by pharmacokinetic test in rats.2.The research of quality criterionThe powder property of the sustained release pellets was studied.The high performance liquid chromatography?HPLC?was used to measure the contents of tanshinone?A,tanshinone?,cryptotanshinone and salvianolic acid B.High performance liquid chromatography and gas chromatography-mass spectrometry were used to study the fingerprints of Danshenyin sustained-release pellets.3.Pharmacodynamical experimentAcute myocardial ischemia model of rats was induced by intraperitoneal injection of isoprenaline,and the contents of MDA and SOD of the water extraction group,supercritical extraction combined with drug residue alcohol extraction group and Danshenyin sustained-release pellets group were detected.Results1.The pharmaceutical technologyAccording to the total extract:microcrystalline cellulose:lactose:0.5%hydroxyl propylmethyl cellose?HPMC?1:1:0.5:0.9,drug residue alcohol extracts and supercritical extracts?add a small amount of alcohol to dissolve?were mixed with 0.5%HPMC,micro-crystalline cellulose and lactose respectively,drying under reduced pressure in 40?,then they were mixed together and pulverizated which could through 200 mesh sieve.The blank pill core was ucrose pill core,50%alcohol was wetting agent,rotational speed was 800 rpm2min^-1,elevation was 40°and the temperature of the roll was 40?,20²4 mesh pellets were sieved out.The pellets were the core,Eudragit NE30D dispersion was used as the sustained-release material;The talcum powder which accounted for 100%of the polymer was an anti-adhesive agent;lactose which accounted for 30%of the polymer was the foramen.The added weight of the coating is 15%,then the sustained release pellets was prepared.Dissolution test in vitro showed that compared with pill,the coating process was stable,pharmacokinetic experiment in vivo proved that the sustained-release pellet had some sustained release effect.2.The quality criterionThe study on the powder property of sustained-release pellets was indicated that it had better roundness;The method was constructed to determine the contents of tanshinone?A,tanshinone?,cryptotanshinone and salvianolic acid B in the sustained-release pellets by HPLC;HPLC and GC-MS were used to establish the fingerprints of the Danshenyin sustained-release pellets.3.PharmacodynamicalCompared with the blank group,the activities of SOD in the rat serum of the model group decreased significantly,and the content of MDA increased significantly?P<0.01?;Compared with the model group,the activities of SOD in the rat serum of Danshenyin extractive group and the slow-release pellet group were increased,and the content of MDA was decreased?P<0.05?.It proved that Danshenyin sustained release pellets had certain anti-myocardial ischemia.ConclusionBased on the previous research of the research group,according to the characteristics of slow-release micropellets,the systematic study of each link in the preparation process is carried out.The experiments of release in vitro and the pharmacokinetic experiment in vivo prove that it can release slowly.And the quality of preparation is controlled by micromeritic properties,content determination,fingerprint and pharmacodynarnics in order to ensure the utility in medication.