The Applications Of Process Analytical Technology To Salvia Miltiorrhiza Ethanol Precipitation And 'YangWei' Granules Spraying And Drying Granulation

Traditional Chinese Medicine (TCM) is a historic industry in China, and its manufacture has been highly depended on experience. An effective on-line monitoring technique is absolutely necessary for the quality control of TCM. As a fast, non-destructive process analysis method, Near-Infrared Spectroscopy (NIRS) technique has been applied in many fields of industry, but a little in TCM manufacturing process. In this thesis, the application of NIRS technique to on-line quality analysis of TCM manufacturing process including Salvia miltiorrhiza ethanol precipitation and 'YangWei' Granules spraying and drying granulation had been researched. The main content was summarized as follows:1. An HPLC method was established for determining gallic acid, albiflorin, paeoniflorin, and benzoylpaenoniflorin in Sugar-free 'YangWei' Granules. The developed HPLC method provided an accurate and sensitive way to quantitative analysis of gallic acid, albiflorin, paeoniflorin and benzoylpaenoniflorin in Sugar-free 'YangWei' Granules. It was suitable for the reference for NIR.2. On the basis of the result of HPLC analysis, taken spray granulation process of 'YanWei' Granules as an example to develop a rapid method to monitor the endpoint in the process of flidized-bed spray granulation. Measure the content of water in products by the NIR model, and use Moving Block of Standard Deviation (MBSD) to judge the endpoint of the process.3. If the parameter was changed, the precipitation result would be changed subsequently. Taking ethanol precipitation process of Salvia miltiorrhiza as an example, the orthogonal experimental design was utilized to choose the most important ones from the following factors: the original cream concentration (ρ), first precipitation stirring velocity (V), first precipitation affiliate rate(x), first ethanol concentration (C), first static time (T), first cold temperature (W) and first frozen time (t). Evaluating with tanshinol content, protocatechuic aldehyde content, solid content and combined score, we found out thatρand C were the most influential factors. In order to verify the results, another experiment was carried out, whose results were consistent.4. On the basis of the results of orthogonal experiments, a NIR method was established to fast distinguish the stability of technics. Taking ethanol precipitation process of Salvia miltiorrhiza as an example, various spectrograms under different conditions were collected. Compared principal component analysis (PCA) models with different pretreatment methods and bands, finally chose the MSC pretreatment and 7070-9500 cm'1 band to establish PCA models. Analysed the spectrograms with PCA method under different ethanol content, batches of cream, cold temperature, sizes containers and numbers of precipitation. And it was found out that the different precipitation conditions could be distinguished using above PCA method.5. An online content analysis method was established to monitor Salvia miltiorrhiza ethanol precipitation process. A partial least squares (PLS) model was established using the selected wave bands, to measure the content of tanshinol, protocatechuic aldehyde and solid matters. It was proved that the model was competent for online analysis of Salvia miltiorrhiza ethanol precipitation process.