Correlation Of Process Changes And Quality Parameters Of Liver Tablets

Objective:To study 4 kinds of quality evaluation parameters of Hugan Pian, including the thin layer qualitative identification, quantitative determination, HPLC fingerprint and dissolution, and establish the evaluation methods. Hugan Pian on sale was measured to analyze the quality differences of Hugan Pian of different sources; using the established quality evaluation methods, the relationship between the process change and product quality was studied, and the scientific and reasonable ranges of process parameters were proposed, in order to provide a scientific basis on the process optimization of actual production of Hugan Pian.Methods:Identifying qualitatively on Schisandrae chinensis fructus, Bupleuri radix and Suis fellis pulvis of Hugan Pian by thin layer chromatography; measuring the content of Schisandrol A, Schisantherin A, schisandrin A and y-Schisandrin by high performance liquid chromatography; establishing the fingerprint of Hugan Pian by high performance liquid chromatography and evaluating the quality of Hugan Pian on sale by similarity degree; measuring the dissolution of Schisandrol A, Schisantherin A, schisandrin A and y-Schisandrin by high performance liquid chromatography, drawing the cumulative dissolution curves, fitting the models and calculating the dissolution parameters; considering the content of 4 kinds of lignans effective constituents of Schisandrae chinensis fructus as the evaluation indexes, to study extraction times in the extraction process of Schisandrae chinensis fructus as single factor, and optimize ethanol concentration, extraction time and solvent times of extraction process of Schisandrae chinensis fructus by central composite design-response surface; to study the types of excipient in the molding process of Hugan Pian as single factor, by comparing the aspects of dextrin and lactose on the above quality parameters.Results:The established thin layer qualitative identification methods of Schisandrae chinensis fructus and Bupleuri radix in Hugan Pian are steady and reliable, available for controlling the quality of Hugan Pian, and there are noticeable differences among sizes and depths of the spots of Hugan Pian of different sources; the established HPLC quantitative determination method of 4 kinds of lignan constituents in Hugan Pian is accurate, simple and feasible, and there are noticeable differences among the contents of 4 kinds of constituents from different Hugan Pian; the established HPLC fingerprint of Hugan Pian is accurate, stable and feasible, which can be used to control the quality of Hugan Pian, and the fingerprint similarity of Hugan Pian of different sources is greater than 0.9; cumulative dissolution curves of 4 kinds of index components in Hugan Pian from different places are noticeablely different, and the results of model fitting of dissolution are also different; the relationship between the extraction rate of lignans of Schisandrae chinensis fructus in Hugan Pian and various factors appears non-linear trend, that is, as ethanol concentration, extraction time and solvent times are increasing, the extraction rate of components climbs up rapidly and then declines slowly, influenced mainly by the ethanol concentration, the better range of extraction process of Schisandrae chinensis fructus in Hugan Pian are the ethanol concentration of 80%to 90%, the extraction time of 1～2.5h, the solvent times of 4 to 6 times, the optimum extraction process is extracting 2 times with 85% ethanol of 4.5 times,1.5h each time; using lactose or dextrin in molding process has no significant effect on quantitative determination of 4 kinds of index constituents, fingerprints and dissolutions, although lactose is better slightly.Conclusion:The quality evaluation methods are reliable and can be used to control the quality of Hugan Pian; according to the results of thin layer qualitative identification, quantitative determination and dissolution, there are noticeable differences among the quality of Hugan Pian of different sources on sale; the significant process changes of Hugan Pian have great impact on its quality, the relationship between the extraction rate of lignans of Schisandrae chinensis fructus in Hugan Pian and various factors appears non-linear trend, the optimum extraction process is extracting 2 times with 85% ethanol of 4.5 times,1.5h each time; the choice of excipients in the molding process of Hugan Pian should be considered according to the actual production costs.