Study On Nirs As A Pat Applied To Monitor Key Manufacturing Processes Of Shenzhiling Oral Solution

With the characteristics of rich resources, unique efficacy, fewer side effects, etc, traditional Chinese medicine (TCM) has a long history and considerable efficacy in prevention, treatment and other aspects of disease. TCM is a complex multi-component system and its production process is complex. Because of the backward production technology and the lack of effective quality control methods in TCM industry, the development of TCM modernization is seriously hampered. Therefore, it is important to develop effective quality analytical tools for process monitoring of the TCM production process for ensuring uniform quality and stability and promoting modernization.It is an effective method to ensure drug quality and uniform that pharmaceutical manufacturing process is monitored and controlled by the process analytical technology (PAT). It can ensure final product quality through timely measurements of critical quality and performance indicators of production process. As a green method of PAT, near infrared spectroscopy (NIRS) has fast analysis speed, non-destruction and high accuracy and other analysis characteristics, making it suitable for online analysis. The application of NIRS is increasingly wide in traditional Chinese medicine industry, showing great potential in qualitative and quantitative determination, online monitoring and process control analysis.Shenzhiling oral solution is one new kind of traditional Chinese drugs exclusively produced by Shandong Wohua Pharmaceutical Co., Ltd., which is the first traditional Chinese drug in internal and abroad for the treatment of Alzheimer’s disease Albert Mertz. In the actual production, the contents of paeoniforin and cinnamic are analyzed for quality control in the end of each unit, the analytical results of which are lagging and can not timely control the producing. Meanwhihe, with the complex system of multi-cmponent synergy requirements, single or minority component parameters are not enough full to describe the qulity of TCM. Besides, to control the quality of the original ingredients is the first step for guarantee the final product quality.Therefore, in order to improve and ensure the uniformity of product quality and the stability of efficacy, and promote the industrialization of Shenzhiling oral solution, the topic is using NIRS to research a rapid process control technique for the water extraction, alcohol precipition and concentrate units of Shenzhiling oral solution production process and a rapid discriminant analysis for original ingredients. The specific studies include below three aspects:1. Establishment of rapid discriminant model of geographical origins for Radix Paeoniae Alba.MicroNIR 1700 near infrared spectrometer was used for distinguishing three geographical origins of Radix Paeoniae Alba, including Bozhou, Heze and Panan samples. With the selections of spectral pretreatments and spectral variables, a steady and reliable qualitative discriminant analysis models was established. The results show that both the recognition and rejection rates of the model were reached 100%, indicting that the developed discrimination model had better predictive ability.Miniature device has volume, light quality, simple operation and is easy to carry so that can better realize the online detection analysis application.2. Rsearch of NIRS technology Process control during Shenzhiling oral solution making.In this study, all process samples were prepared under laboratory scale simulating the actual production process. NIR spectra of samples were collected by means of using Antaris II FT-NIR spectrometer with transmission module and the reference values wrere measured mainly by HPLC method. PLSR, SVMR, etc, were applied to associate sample spectra datas with the reference datas to establish quantitative analysis model for each process parameter. Robustness and predictive abilities of the model were optimized through spectral preprocessing and spectral region selection. This experiment investigated the quality control of alcohol precipitation, alcohol precipitation concentration and peony water extraction sectors in Shenzhiling oral solution production process. The detail results were following:(1) Water extraction process of Radix Paeoniae Alba:rapid determination models of the process contents of paeoniflorin, albiflorin, gallic acid, benzoyl paeoniflorin were developed, and the RMSEC, RMSEP, R2cal, R2val, RPD of each model were respectively:paeoniflorin 0.0487,0.0545,0.9873,0.9855,8.4; albiflorin 0.0303,0.0321,0.9879,0.9888,9.1; gallic acid 0.0134,0.0145,0.9721,0.9697,5.1; benzoyl paeoniflorin 0.00188,0.00177,0.9745,0.9789,6.7.(2) Alcohol precipitation process:rapid determination models of the process contents of albiflorin, paeoniflorin, glycyrrhizin, cinnamic acid, licorice acid were developed, and the RMSEC, RMSEP, R2cal, R2val, RPD of each model were respectively:albiflorin 0.0281,0.0305,0.9914,0.9927,10.2; paeoniflorin 0.0849, 0.0733,0.9933,0.9976,14.7; glycyrrhizin 0.0120,0.0123,0.9553,0.9761,5.1; cinnamic acid 0.00389,0.00289,0.9588,0.9903,7.1; licorice acid 0.0538,0.0590, 0.9820,0.9863,7.2.(3) Concentration of alcohol precipitation solution:apid determination models of the process contents of paeoniflorin, albiflorin, licorice acid, glycyrrhizin, cinnamic acid and density were developed, and the RMSEC, RMSEP, R2cal, R2val RPD of each model were respectively:paeoniflorin 0.2231,0.2360,0.9914,0.9887,9.3; albiflorin 0.1518,0.1307,0.9658,0.9708,6.1; licorice acid 0.0891,0.1697,0.9923,0.9670,5.2; glycyrrhizin 0.0183,0.0138,0.9744,0.9801,6.4; cinnamic acid 0.0170,0.0181, 0.9521,0.9402,4.0; density 0.0091,0.0096,0.9874,0.9938,8.5.Compared with the reference methods, the NIR spectroscopy models can significantly save manpower and time, and useful to control the production process timely and ensure the stability of the production process, which was in favour of ensure uniform product quality.