Application Research On Process Analytical Technology In Manufacturing Process Of Two TCM Injections

The present quality control of traditional Chinese medicine (TCM) injection is usually performed in intermediate or final products by traditional analytical methods. However, in-line monitoring of key manufacturing units has been rarely reported. It must result in a delay of analysis time, the lack of feedback-control without useful information and the reduction of homogeneity between batches. With the advantages of rapidity, accuracy, no destructivity and no pollution, process analytical technology (PAT) including near infrared spectroscopy (NIRS) can solve the problem of TCM manufacturing being lack of quality control. In the paper, the application of suitable PAT tools had been investigated in manufacturing processes (raw material, extraction, ethanol precipitation, purification and etc.) of "Cinobufacini Injection" and "Scutellarein Injection". The study was aimed to realize the whole processes of TCM manufacturing, which had a profound effect in modern TCM development. The main research achievements are as followed:1. NIRS was used in establishing a multivariate calibration model for the raw material of Cinobufacini Injection, dried toad skin. It can analyze serotonin, bufothinoine, bufalin, resibufogenin, cinobufagin and protein simultaneously. The results showed that the easily operated method can fast judge the quality of toad skin.2. NIRS with various chemometrics was developed to build both quantitative method to monitor indole alkaloids concentration and qualitative method to judge the end point in 1st and 2nd extraction processes of Cinobufacini. The result suggested this method can reflect indole alkaloids concentration change and help determine the end point in extraction process。3. NIRS was established to predict the content and transfer rate of indole alkaloids of in ethanol precipitation of Cinobufacini. It was concluded that NIRS could be applied in the process of ethanol precipitation.4. NIRS was proposed to analyze scutellarein concentration in purification process by macroporous resins. Also, the stability of NIRS model was investigated in different operating conditions. The results demonstrated it could be used in in-line monitoring process of macroporous resin purification. 5. Focused beam reflectance measurement (FBRM), particle video microscope (PVM) and NIRS were utilized to monitor multi-information including chord count, chord length distribution, particle shape and scutellarein concentration in antisolvent crystallization of scutellarein. The above combined technology is the first usage in TCM injection in the world. This method provided more actual data and made a more comprehensive understanding of antisolvent crystallization.