Studies On Techniques About Intelligent Release Methods Of Key Production Section Of Reduning Injection

Reduning injection is made from Artemisiae Annuae Herba,honeysuckle Lonicerae Japonicae Flos and Gardeniae Fructus with heat,dispelling wind,detoxification effect.Reduning injection is commonly used to treat fever,headache,cough,phlegm and inhibition of influenza virus caused by upper respiratory tract.Studies have indicated that phenolic acids compounds are the main anti-viral and anti-inflammatory ingredients of the injection.At present,the quality test methods of Reduning injection products still rely on the sampling test of intermediates and final products.And this doesn’t conform to the idea thatthe quality of the products is not determined by test but design.Also,the traditional off-line sampling test has the disadvantages of high hysteresis and labor costs.To accelerate the intelligent development of Chinese medicine production,the release methods must be shifted from experience verification and off-line sampling test to intelligent release through digital control technology and mathematical model.The digital control technology and mathematical model can drastically reduce labor costs and time costs,ensure the quality of products point-to-point,process to process and batch-to batch,and ultimately improve product quality and stability,which will improve risk management and control capabilities.Taking the key production section of Redunig injection as an objective,this paper tried to explore the feasibility of intelligent release of the key production sections of Redunig injection by using the assessment of process capability design space methods and the monitoring of process trajectory.1.The process performance index(PPI)was used to evaluate the quality of the intermediates and the quality consistency between batches.In this paper,the process performance index and Bootstrap algorithm were used to calculate the PPI of key production sections and confidence interval of PPI.The results showed that the capacity of honeysuckle extraction enrichment section reached the production requirement,and the process trajectory map could be directly established for the monitoring of the whole process.The capacity of ethanol precipitation and concentration section did not meet the production standard,which means the release range of process parameters of this section needed to optimize by design space method,and then establish the process trajectory map to monitor the whole process.2.To optimizing the release range of process parameters using the design space method,firstly,in thisstudy,process input data and process output data through the PKS platform was collected,secondly,the critical process parameters(CPP)through the PKS platform RSD analysis and correlation analysis function module were screened out.Then the mathematical model between the CPPs and the critical quality attributes(CQA)was established by the stepwise regression method.Finally,the design space was calculated by MODDE software.The results showed that the quality of Artemisia annuus ethanol precipitation and concentration section optimized with the design space were relatively stable,and the process capability was greatly improved.3.Establishing the production process trajectory.To realize the entire production process online monitoring,in this paper,first of all,the data of near-infrared spectroscopy of multiple batches of key production processes were collected,and the multivariate statistical control technique was used to establish the process trajectory to realize the full monitoring of the production process.The results showed that the primary components score,Hotelling T2 and DModX locus of the key production sections of RT-injection could detect abnormalities of the process,indicating that the process trace based on near-infrared spectroscopy data and MSPC technology can reflect the production of process changes and can be used to monitor the full production of Chinese medicine.