Technological Optimization And Preliminary Study On Stability Of Tongmai Dasheng Tablets

Tongmai Dasheng Tablet is a prescription for the treatment of infertility based on many years’clinical experience,which was concluded by Zhuo Yunong,a famous gynecologist of traditional Chinese medicine.And it was transformed into a hospital preparation of Affiliated Hospital of Chengdu University of Traditional Chinese Medicine.Tongmai Dasheng Tablet is composed of 11 kinds of medicines,such as Salviae Miltiorrhizae Radix et Rhizoma.（SMRR）,Paeoniae Radix Alba（PRA）,Astragalus membranaceus（Fisch）Beg.var.mongholicus（Beg.）Hsiao（AMBMH）,Angelica sinensis（Oliv.）Diels（ASD）,Lychium barbarum L.（LBL）.It has the functions of tonifying kidney,nourishing blood and regulating menstruation.It has a good clinical effect on ovulation disorder infertility.The original preparation is plain tablet,because it contains a large number of animal medicine powder,which smells bad,and takes a large amount of it,so it is difficult for patients to swallow.The purpose of this research is to optimize the preparation process to meet the requirements of film coating,so as to cover up the odor.The quality standard was established,and the factors affecting the stability of the preparation were preliminarily explored.According to the original preparation method,the hardness of the tablets can not meet the coating requirements.Because the size of the raw powder is too large,the tablet is not compact,and the bonding effect of the adhesive is not enough,the tablet hardness is low.Therefore,in the preparation process of tablets,three crushing methods and the best particle size standard of the crushed medicinal materials are mainly investigated,and the forming process of tablets is optimized.To improve the dissolution of SMRR and PRA in Tongmai Dasheng Tablets（TDT）,and construct a good powder dispersion.SMRR,PRA,and Placenta Hominis（PH）were crushed by common method and ultramicro method using calgon as a dispersant to prepare 19powder dispersion samples.The particle size distribution,infrared spectrum,dispersion,specific surface area,and porosity of the powder dispersions were investigated.The content of salvianolic acid B and paeoniflorin were measured by HPLC,and the dissolution of salvianolic acid B and paeoniflorin in different powder dispersions was evaluated.Infrared spectrum results showed that superfine pulverization,mixed comminution or adding the auxiliary pulverizing cannot produce new substances in medicinal powder.The dissolution rate of salvianolic acid B and paeoniflorin in the mixed ultramicro powder dispersions of SMRR and PRA was the highest,salvianolic acid B 83.57%,RSD 2.03%,paeoniflorin 80.75%,RSD 0.61%.The dissolution rate is affected not only by the specific surface area of the powder but also by the dispersity of the powder.In order to improve the dissolution rate of active ingredients in powder,it is important to increase the specific surface area of the powder and improve the dispersity of the powder.In the mixed powder of SMRR,PRA,and PH,the dissolution rate of salvianolic acid B and paeoniflorin was lower than that of the mixed powder of SMRR and PRA.Hence,PH was smashed alone,and then mixed with the other two kinds of medicinal powder.In the investigation of moulding technology,the excipients and dosage of the preparation were optimized,and the types,concentration and dosage of the binder,drying time of the particles and dosage of lubricant were investigated.The water content,moulding rate,fluidity,disintegration time,hardness and dissolution rate of the effective components of the tablets were determined.The final forming process is as follows:microcrystalline cellulose as excipient is mixed with three kinds of original powder and extract powder evenly,adding 35%starch slurry,stirring and mixing evenly,then granulating,drying temperature of the granule is 60℃,drying for2 hours,whole granule,adding 3%magnesium stearate of the total granule,mixing evenly,pressing tablets.The weight of the adjusting tablet is 0.3 g and the hardness is controlled above 40 N to ensure the coating condition.The coating agent was selected to coat the tablets.The solid content of the coating solution was 20%,the coating quality was increased by 3%,the temperature of the tablet bed was 45℃,the flow rate was 2 g·min^-1,and the speed of the coating pot was 70 r·min^-1.The disintegration time of coated tablets met the requirements.In the aspect of quality standard research,TLC method was established to identify five traditional Chinese medicines,SMRR,AMBMH,ASD,LBL in turn.The method was feasible and had no negative interference.An HPLC method was established to determine the contents of salvianolic acid B,paeoniflorin and mulberry isoflavone glucoside.The content of salvianolic acid B in each tablet should not be less than 1.6 mg,paeoniflorin should not be less than 0.8 mg,and the content of isoflavone glucoside should not be less than 0.011 mg.In the aspect of preliminary stability study,an HPLC method was established for simultaneous determination of tanshinol,protocatechuic acid,catechin,paeoniflorin,mulberry isoflavone glucoside,shikonic acid,salvianolic acid B and benzoyl paeoniflorin.The effects of different temperature,humidity,illumination conditions and packaging on coated and plain tablets were investigated.The moisture absorption rate and the content of active ingredients in tablets were determined.The variation of the content of active ingredients with temperature,humidity and light was analyzed.The effects of different packaging methods on the components were also analyzed.Storage conditions of this product should be controlled at 25℃and humidity within45-75%.Tablets should be kept away from light.