Preparation Technology And In Vitro-in Vivo Evaluation Of Shunxin Sustained Release Granules

Objective: To prepare the Shunxin sustained release granules and to evalute its drug release behavior in vivo and in vitro,in order to improve the bioavailability of main indicative ingredients in Shunxin sustained release granules.Methods: 1.To prepare the Shunxin sustained release granules.The contents of tanshinoneⅡA,ginsenoside Rb1,paeonol,paeoniflorin,calycosin-7-glucoside and ferulic acid in Shunxinzufang extracts were detected,to determine whether of the water extract or alcohol extract was used for granulating.According to the formability,homogeneity,fine powder rate and fluidity(angle of repose)to selecte preliminary filler and sustained release material.The single factor test was used to determine the ratio of Shunxinzufang extract in whole prescription and sustained release materials/filler ratio.2.To optimize its excipient prescription and in vitro release test.In the above-mentioned single factor tests and pre-test results,choosing the proportion of Shunxinzufang extract(%)and sustained release material/filler as the investigation factors,the two-factor five-level test was carried out.The cumulative release of paeoniflorin,calycosin-7-glucoside and ferulic acid in 2 h,6 h,12 h respectively was used as the response value,and combined central composite design(CCD)with response surface method(RSM)to further optimize the excipient prescription of Shunxin sustained release granules.Then Shunxin sustained release granules were prepared with optimal preparation conditions and its release behavior was evaluated through in vitro release test.3.Pharmacokinetic study.Six New Zealand white rabbits were divided into shunxinzufang extract group and shunxin sustained release granules group according to the above optimal preparation conditions.The pharmacokinetics of two groups were studied by oral administration.Each 2 mL of blood was taken from the heart at 0.25,0.5,1,2,4,6,8,10,12,24,36 h after administration,and it was treated in a heparinized centrifuge tube.The plasma concentrations of paeoniflorin,calycosin-7-glucoside and ferulic acid in plasma were determined by high performance liquid chromatography.The data were processed by DAS 3.2.7pharmacokinetic software to calculate the relevant pharmacokinetic parameters.Results: 1.According to total amount of extract and main indicative ingredients of two kinds of extracts,the water extract was used as the main raw material for the preparation of Shunxin sustained release granules.The preliminary screening of the excipient and the single factor test show that the basic prescription of the excipient materials are: corn starch used as filler and hydroxypropyl methyl cellulose(HPMC)used as sustained release material.Paeoniflorin,calycosin-7-glucoside and ferulic acid were chosen as the main indicative ingredients for the detection and evaluation of the subsequent tests.2.The optimal preparation conditions of shunxin sustained release granules obtained by CCD and RSM optimization were: 35% Shunxinzufang extract,65% HPMC and corn starch(HPMC/ corn starch =2:1).It was verified that the measured value of the response is close to the predicted value under the optimal preparation conditions.The Shunxin sustained release granules prepared under the optimal preparation conditions have a certain sustained release behavior.3.Compared with Shunxinzufang extract group,the peak concentration and area under the drug-time curve of paeoniflorin,calycosin-7-glucoside and ferulic acid were all high in Shunxin sustained release granule group.The peak time,mean residence time(MRT),and half-life are prolonged in Shunxin sustained release granules group.The data illustrated that Shunxin sustained release granules have obvious sustained release characteristics.Conclusion: 1.By detecting the content of the main indicative ingredients in Shunxinzufang decoction and preliminary screening of the excipients.The water extract was selected as the raw material,HPMC as the sustained release material,and corn starch as the filler.2.CCD and RSM were applied to optimize excipients prescription for Shunxin sustained release granules.The optimal preparing prescription of Shunxin sustained release granules were 35% shunxinzufang extract and 65% HPMC/corn starch(HPMC/corn starch ratio=2:1).3.The pharmacokinetic study of Shunxin sustained release granules showed that,compared with the shunxinzufang decoction,Shunxin sustained release granule have obvious sustained release characteristics,and better bioavailability of paeoniflorin,calycosin-7-glucoside and ferulic acid.