Study On Optimization Of Pushen Capsule Processing Technology And Its Quality Improvement

Pushen Capsule consists of eight Chinese medicine such as Puhuang,Polygonum multiflorum,Chuanxiong,red peony,ect.The current process has the problems such as hygroscopic,imperfect quality control problem.We used the modern technology to optimize the subject of the production process and improved quality standards.Study includes literature,process optimization,quality standards improvement and stability.Ⅰ Literature StudyReferenced to Chinese medicine theory,it explains Pushen capsules prescription,We summarize according to pharmacology,toxicology,clinical and other aspects of Pushen capsules safety,effectiveness,etc.;We also conclude from eight herbs such as physicochemical properties,pharmacology and other aspects of prescription Puhuang,Polygonum multiflorum.Ⅱ Process Optimization StudyPolygonum was crushed into powder in the original production process;Puhuang,red peony,Salvia and other seven herbs flavor boiling water 2 times,the extract was concentrated to a thick paste and Polygonum powder after mixing,drying,grinding into powder.Then add the paste fine amount,granulation,drying,whole,into the capsule.Puhuang,Chuanxiong,red peony root and other herbs contain volatile oil.The original process is not carried out volatile oil extract,.After Polygonum playing powder medicine,materials forming contains a small space.According to the nature of the active ingredient prescription drugs,design and conduct research process route.Then compare the original process and the optimized.1、Extraction Process Study(1)Volatile oil extraction rate is used as the indicators according to the nature of herbs medicinal ingredients.volatile oil were extracted in Puhuang,Chuanxiong,red peony root and other herbs considering soaking time,adding water,extraction time.orthogonal design is designed to see how different factors factor levels effects oil.the volatile oil extraction process:plus six times the amount of water,soak 1h,e xtraction 3h.Under these conditions,volatile oil extraction rate is to 80%,while the original process is not reserved for the extraction of essential oil.(2)Liquid paeoniflorin extraction rate is used as the index with solvent ratio,extraction time,extraction times as factors.The extraction technology is studied with the orthogonal design,the extraction process is proved to be:1.0 hour extraction after adding seven times the amount of water,then filtration,then extraction again for half an hour after adding 5 times the amount of water.After process optimization paeoniflorin in liquid withdrawal rate is about 30%.Extraction technology is compared before and after the optimization,with total extraction yield of 67.2%before,91.2%after respectively.(3)Using the hawthorn,salvia,Polygonum shamisen herbs in flavonoids,stilbene glycoside extraction rate as indicators to investigate the factors as ethanol concentration,extraction times,plus the amount of alcohol,extraction time,The extraction process is proved as follows:adding 12 times the amount of 80%ethanol and heated to extract 1.5h,filtration,dregs adding 7 times the amount of 80%ethanol and heated to extract 1.0h,filtration,dregs adding 7 times the amount of 80%ethanol extract heat 0.5h,filtration,combined filtrate.Tetrahydroxystilbene transfer rate of about 97%.2、Concentration and Purification Process Study(1)Water extract Paeoniflorin is used as an index to a concentrated alcohol precipitation study according to extraction process(2).It is proved that the extract was concentrated under reduced pressure to adopt the relative density of 1.15 to 1.20 with concentration of alcohol precipitation 70%.Enrichment process optimization were compared before and after the two craft is close.Before and after optimization process Paeoniflorin metastasis rate is 97.5%and 96.6%respectively.(2)transfer rate is used as an index for the concentrated for the method and temperature inspection of the concentration.The results preferably 60℃concentrated under reduced pressure.Tetrahydroxystilbene transfer rate is about 97%;right to concentrate stilbene glycosides,flavonoids transfer rate,extracts impurity yield indicators were investigated to determine the impurity removal process:adding concentrated liquid volume of 16%1%ZTC B flocculation impurity solution,then add 8%solution of 1%ZTCA flocculation.Under this condition,extract yield increased from 23%to 14%,while stilbene glycosides,flavonoids transfer rate is about 99%3、Drying Process Study(1)Paeoniflorin content acts as indexes after drying methods in extraction process(2),Comparing drum wind drying and vacuum drying,no obvious difference is found between the results obtained in the concrete content.Finally the vacuum drying method is adopted.(2)Liquid removed impurity after concentration and purification process extract powder after drying toluylene glycosides content as an index for the drying process,te result turned out to be the spray drying method.Drying process before and after the optimization are compared,and the second styrene glycosides metastasis rate are 99.3%,98.8%,respectively.4、The molding Process Study(1)Volatile oil are studied in β-cyclodextrin and inorganic adsorption according to the extraction process(1).The results choose volatile oil two times the amount of silica adsorption.According to the volatile oil extraction rate,finally decide to add 10g silica per prescription.(2)Mix the powder in the drying process(1)and(2).particle characteristics,mobility,moisture absorption and finished disintegration time are acting as the indexes to do the study of prescription screening and forming.Then form each x 1000 grains priscription process:mix water extraction and alcohol extract extract powder,add the total weight of the mixed extract lactose C80 to mix;take 5%of the total extract materials PVPK30,with 80%ethanol solution made of 10%PVPK30:Add mixed extract excipients,24 mesh granulation,granules dried at 60℃,20 mesh whole;take 10g of silica after adsorption of volatile oil and grain mix.Materials for Comapring the space,fluidity,moisture on the before and after optimization.Finally,results of the optimized space for product materials,angle of repose,the critical humidity are 50～55%,30°,75%respectively while 4～8%,35°,50%respectively before optimization.Ⅲ Quality Standards Improvement StudyOriginal quality standards,in addition to conventional capsules check items,there are Polygonum,salvia root,Codonopsis TLC and emodin content.Improve quality standards ascension multiflorum,Salvia(protocatechuic aldehyde),Chuanxiong,Codonopsis TLC and add Salvia Tan || A TLC and increas the dissolution test finished products.In addition to the original standard assay determination of emodin outside,also add Paeoniflorin,stilbene glucoside content.Add raw materials,intermediates and finished fingerprint.1、TLC study(1)In Polygonum TLC,the extraction solvent reagent is replaced to methylene chloride from a stair toxic one.Before and after optimization in the process control medicine,standard corresponding position are yellow spots.The color of spot turns dark red after ammonia vapor.Spots are more after optimization.(2)Protocatechualdehyde is added in the identification items of Salvia.Instead of toxic chloroform we use methylene chloride.Before and after optimization are finished with the reference substance corresponding position display spots,but the spots on the finished product is much more clear than before optimization(3)Salvia Tan || A is added in identification items and solvent extraction is dichloromethane.A corresponding position are the same dark red spots in Tanshinone || after optimization,while no spot before optimization(4)In chuanxiong TLC,use the extraction solvent dichloromethane instead of toxic reagent chloroform.At the corresponding position is the same color spots,but fluorescent spots are stronger than before optimization(5)In codonopsis TLC,use the extraction solvent dichloromethane instead of toxic reagent chloroform.At the corresponding position are the same color spots.but the optimized spots are more and the separation is better.2、The Dissolution TestPaeoniflorin and Toluylene glycosides dissolution rateacting as the indicators examines the dissolution medium,the dissolution method,dissolution speed,etc.,The results shows puttint a Pushen,capsule in 250mL 0.5%Tween 80 solution,37℃,adjusting the speed 50rpm for dissolution test.The optimized products Paeoniflorin,cumulative dissolution rate of stilbene glycoside ordinate,with time as the abscissa the elution curves and calculate Paeoniflorin,stilbene glycoside dissolution parameters T50,Td,m,optimized product Paeoniflorin dissolution parameters are 7.14min,8.58min,2.14,and the dissolution parameters stilbene glucoside are 8.00min,9.70min,1.90.Before and after optimization product for dissolution test,the results before and after optimization products are basically the same with Paeoniflorin dissolution rateare 97.1%,99.2%,but after optimization tetrahydroxystilbene dissolution rate is significantly higher than before which are 97.6%,37.2%respectively.3、Content Determination(1)Add paeoniflorin,stilbene glucoside content determination.Using a gradient elution,different time periods set different wavelengths of linearity,precision,solution stability,repeatability,sample recovery,and other related methodological research.This method is feasible to determine the two effective ingredient content with better liquid measurement conditions.After testing the samples,the Paeoniflorin contents are 0.63mg per capsules and 1.02mg per capsules before and after optimization,with stilbene glucoside content are 1.30mg per capsules and 1.23mg per capsules.(2)Using the original quality standards determination method for emodin.After testing the samples the emodin content are 131μg per capsules and 87.5μg per capsules before and after optimization.4、Fingerprints(A)Establish a raw material fingerprints including Puhuang,Polygonum,salvia,red peony root,Chuan Xiong.Precision,solution stability,repeatability and other methodological study are carried out.The results of the method are feasible.Puhuang,salvia,red peony root,Chuan Xiong fingerprint’similarity reach more than 0.9.Polygonum fingerprint similarity reachs 0.8 or more.(2)Established the intermediates fingerprints including intermediates water extraction,alcohol intermediates).Precision,solution stability,repeatability and other methodological study are carried out and the results of the method are feasible.Water extraction intermediates and intermediates alcohol fingerprints’similarity reach 0.9.(3)Establish a finished fingerprints.Precision,solution stability,repeatability and other methodological study are carried out and the results of the method are feasible.Fingerprint patterns are established and refined fingerprint similarity reached 0.9.IV Stability StudyReference to the establishment of quality standards,CP 2010 edition and related guidelines,the samples are in long-term stability condition(25℃±2℃,RH60%±10%),accelerated stability conditions(40±2℃,RH 75%±5%)under storage,long-term stability at 0 months,three months,six months recording inspection results,accelerated stability test at 0 months,one month,two months,three months,six months record inspections.Results show that the indicators in the long-term stability under accelerated stability conditions do not chang significantly in the six months.So indicate that the optimized product is stable during the study period.V Characteristics and Innovation1、In the molding process use a new alternative C80 instead of dextrin,solving the problem of high hygroscopicity and environmental requirements,but also ensure the dissolution of products.2、Adding the determination of stilbene glycosides,paeoniflorin,solve the detection problem with different components and different absorption wavelengths in the same condition.When used in the determination of the gradient mobile phase,different time periods set different wavelengths.