Study On Quality Evaluation Of Chinese Medicine Solid Preparation Based On The Determination Of Dissolution Rate

The dissolution testing is the soul of solid drug evaluation and an important tool for its quality control in the developed countries. But Chinese medicine solid preparations (CMSP) only think highly of extraction, depuration and separation, usually neglect the forming process. This study emphasizes the significance of dissolution testing of CMSP, which could promote the whole pharmaceutical industry development and related industries. In case of the complexity of the dissolution testing of CMSP, we develop a new evaluation method for controlling the quality of CMSP, which analyzes the limitations of present dissolution testing study from active ingredient TCM and compound TCM.1 The quality control mode of chemical synthetic drugs could be used as reference for the production of solid preparations from effective components of TCM. The difference in dissolution curve between tested preparation and reference preparation (or original drug) was evaluated by using similarity factor f2. The evaluation parameters were used in optimizing formula, screening process and monitoring quality according to preset standard dissolution curve. If there is no reference preparation, the condition for dissolution experiment should be set strictly to enforce enhancing and improving preparing technology. The correlativity between in vitro dissolution and in vivo bioavailability could be established effectively.In this paper, with ursodeoxycholic acid capsule (Ursofalk) possessing exactly clinical curative effect as reference preparations, its dissolution curve was used to guide formula optimization and technology screening of self-made tablets. Till the similarity factor f2 of dissolution curves between self-made tablets and Ursofalk was higher than 50. The final similarity factor f2 was 55.96 in our experiment, and then the optimum formula and technology of simulated drug were ascertained. Simultaneously, the pharmacological verification experiment was performed on the function of normalizing gallbladder to cure jaundice of ursodeoxycholic acid. Compared with the models, the bile flow was significantly reduced and the serum ALT, AST, ALP, GGT and TBIL levels decreased of experiment group (P<0.01), which was similar to the bile flow in Ursofalk group. Besides, the serum total bilirubin level of experiment group was lower than that of Ursofalk group. The results showed that the self-made tablets had good function of promoting bile acid excretion and bile excretion. It was equipotent to Ursofalk based on dissolution testing.2 The efficacy of solid preparation of Chinese medicine formulation is the result from co-compatibility and interaction of multiple components. If the quality control mode of chemical synthetic drugs is still used as reference, i.e. quality control and evaluation was achieved by using one or a few index components in qualitative and quantitative determination and analysis, the result may be different from holo-efficacy, so the quality of solid preparation of Chinese medicine could not be evaluated comprehensively. In order to make new breakthroughs in dissolution analysis of solid preparations of TCM, we tried to establish chemical analysis-biological potency associated detection method to objectively characterize in vitro dissolution of solid preparations of TCM and to further supplement the deficiency in present quality control and evaluation method for solid preparations of TCM, which only took chemical components determination into consideration.To explore the new pattern of solid preparation of Chinese medicine in vitro dissolution testing, a method based on the bio-thermal activity in combination with UPLC was used. Microcalorimetry was used to obtain the characteristic metabolic growth power-time curves and a series of biothermodynamic parameters of the inhibition of Staphylococcus aureus by Yinhuang tablet dissolving solutions at the pH 6.8 (phosphate buffer) dissolution medium at different times. From these results, the cumulative dissolution of Yinhuang tablet based on bio-thermal activity was obtained. The dissolution rates of two components of chlorogenic acid and baicalin were determined by UPLC method. Then f2 similar factor method was used to evaluate the relevance of these two methods. The result showed that f2 values all were more than 50, indicating that there is a good correlation between the two methods of measuring the dissolution rate. It is feasible to determine CMSP in vitro dissolution by using bio-thermal activity, and to provide new evaluation methods for controlling the quality of CMSP.