Research On Production Technology And Quality Standard Of Si Ji Gan Mao Tablets

Si Ji Gan Mao Tablets consists of nine herbs:Tangerine peel,Schizonepeta,Purple perilla,Folium isatidis,Fructus forsythiae,Glycyrrhiza,Radix sileris,Rhizoma cyperi,Platycodon grandiflorum.It has the function of clearing heat and solving surface.The curative effect of this product is stable for pure Traditional Chinese medicine preparation,and no obvious toxic and side effects have been seen since it came into the market.Reasonable preparation process is a key link in the research and development of traditional Chinese medicine compound.Stable and reliable preparation process can not only guarantee the efficiency of the final drug to a great extent,but also play a positive role in clinical medication.The subject has made a systematic study of Si Ji Gan Mao Tablets which includes extraction process,concentration and preparation process,quality standards,stability examination and so on.The aim is to extract the active ingredients to the maximum extent in the preparation process,and the product quality is supported by strict quality standards.Volatile oil is one of the main components of Si Ji Gan Mao Tablets.The extraction process of essential oil was simply described in the original production process:The volatile oil was extracted from Perilla leaves,dried tangerine peel and Schizophylla,and then the aqueous solution was distilled and collected in another device.The extraction process of volatile oil is not carefully described and the volatile oil can be easily lost in the process of preparation spraying and particle drying.The problem is a key factor affecting its effectiveness.In order to ensure the curative effect of the preparation,the inclusion technology of volatile oil cyclodextrin was studied.The extraction process of volatile oil was optimized by orthogonal experiment,and the best extraction process of volatile oil from Si Ji Gan Mao Tablets was concluded as follows:the medicinal materials were soaked for 1 hour,10 times of water was added,and the volatile oil was extracted by distillation for 5 h.At the same time,in order to ensure the curative effect of the preparation and reduce the loss ofvolatile oil,the inclusion technology of volatile oill cyclodextrin was studied,and the optimum inclusion technology was determined by orthogonal test and validation:the amount of essential oil added was 1.2ml,the stirring temperature was 40?,and the stirring time was 4 h.The water extraction process of seasonal cold film is not carefully described.Only the extraction solvent of the leaves,forsythia,and licorice were specified,but the technological parameters of the extraction process were not clearly required.The process of alcohol extraction is similar to that of water extraction,only the solvent and number of extractions are specified.However,the technological parameters of the extraction process are not clearly required.And with the improvement of the existing production equipment,the extraction solvents and extraction times in the original standard need to be scientifically verified.The above problems all reflect the uneven quality of cold tablets in the current market,lack of detailed,stable and feasible preparation technological parameters,and low bioavailability,which is not conducive to the production and clinical application of this prescription.In this study,the water extraction process and alcohol extraction process are studied in detail,and accurate and specific process parameters are obtained.L9(34)experiment was designed for water extraction process and alcohol extraction process.Water addition,extraction time and extraction times were used as indexes for comparison.The water extraction process took the total amount of water extract and the content of Forsythiin as indicators,and finally determined the water extraction process as follows:the crude drug was extractedtwice,the first time with 10 times of water,distillation for 2 h,and the second time with 8 times of water for 2 h.The alcohol extraction process was based on the total amount of the alcohol extract and the content of Prim-o-glucosyl-cimifugin and 5-o-methyLvisaminoGlyco-side.The final alcohol extraction process was determined as follows:60%ethanol was extracted twice,the first time was added with 12 times of 60%ethanol for 2 hours,and the second time was added with 10 times of 60%ethanol for 2 h,combined with the extraction solution and filtered.With the increase of the market demand for Si Ji Gan Mao Tablets,the previous process parameters correspond to the old tablets pressing equipment,and the production efficiency is low,far from meeting the market demand of the product;In addition,at present,the relative density of water extract paste and alcohol extract paste is relatively high,the atomization droplet viscosity during granulation process is large,and the atomization pressure requirement is high.In actual production,there is always the phenomenon of material caking "stepping bed",resulting in uneven granulation and more fine powder.It not only affects the production efficiency of pelleting,but also affects the quality of pressing process.To adapt the product to modern industrial production,the granulation process of water extract and alcohol extract with different relative densities was studied.The effects of different densities of water extract and alcohol extract on granulation smoothness and granulation uniformity were investigated.Finally,it was determined that the optimal density was 1.26-1.30(60?65?)of alcohol extract paste and 1.26-1.30(60?65?)of water extract paste.The microcrystalline cellulose was selected as the medicinal auxiliary material of the four seasons cold tablets.When the dosage of the microcrystalline cellulose was 20.8%,the tablets weight was about 0.48g.Fluidized bed one-step granulation is a combination of mixing,drying and granulation.It has the characteristics of high efficiency,good controllability and less amount of excipient materials.The one-step granulation method of fluidized bed is adopted to Si Ji Gan Mao Tablets.Finally,the content of this product in the original national drug standard(WS3-B-2499-97-9)was determined by TLCS.TLCS quantitative determination is more complicated than HPLC,with poor specificity,low sensitivity and poor repeatability.The quality standard of Si Ji Gan Mao Tablets was formulated,and the characteristics,identification and content determination of forsythia in the identification were stipulated respectively,so as to establish a perfect quality standard.The stability of seasonal cold tablets was studied,accelerated test and long-term test were carried out respectively,and the stability of the products was measured according to the newly established quality standards according to the time node,and the maturity of the process of the products was verified.