| Objective: According to Provisions for Drug Registration, the technique guiding of traditional Chinese medicine(TCM) and natural medicine and the requirement of modern pharmaceutical technologies, the comprehensive and systematic studies on preparation, quality control and stabilities of Rhizoma Coptidis Formula Particle were accomplished. The research results indicated that the preparation was safe, effective, stable and controllable.Methods:1 Studies on the preparation process1.1 Extraction process The water extraction process was optimized by using orthogonal test(L9(3)4), using the content of paeoniflorin as indicator. Extraction times,duration, additive water amount were the investigation factors, followed by a verification tests of the optimized conditions were conducted to determine the final extraction process.1.2 Spray granulating process The pray granulating process with the fined powder of Radix Trichosanthis as the basic material was optimized by the consideration of the capacity of spray granulation, the obtained amount of particles and the proportion of particles passed through a 32-mesh sieve as indicators to determine the main parameters: relative density of the solution, frequency of infusion pump, temperature of main and auxiliary fan and drying time. Spray granulation process parameters were finally determined with the consideration of actual situation.1.3 Preparation process Particles, prepared using the spray granulation processes, were used in the preparation process. Three batches of pilot plant products were manufactured accordance with the established process.1.4 Studies on examination The general requirements of particle were carried out in accordance with the method of Chinese Pharmacopeia, three batches of pilot plant were determined as the described method.2 Studies on the quality The three batches of pilot plant were used to study and develop the quality standard of Rhizoma Coptidis Formula Particle, including thin-layer chromatography(TLC), quantitative analysis, general requirements of particle.2.1 Identification of thin-layer chromatography The TLC method was employed to optimize the identification method of the Rhizoma Coptidis Formula Particle, including the preparation of test solution, developing solvent and checking method.2.2 Quantitative analysis HPLC method was developed and validated to determine the content of paeoniflorin, the content limitation was determined by the consideration of transfer rate and the final quality standard was established.Results:1 Preparation process1.1 Extraction process To optimize extraction process by adopting orthogonal test: extract two times with 8 times of water, each time 1h.1.2 Spray granulating process Optimized spray granulating parameter as follows: Infusion Frequency:2.5~3.0Hz; main fan temperature: 70~80℃; auxiliary fan temperature: 60 ~70℃; dring temperature: 60~70℃(2h). The relative density of liquid was designed at the range of 1.10~1.15(60℃).1.3 Examination results The examination results indicated that three batches of samples(070401、070701、070904) were consistent with the requirements of capsules.2 Results of the quality standard2.1 TLC The TLC methods of Rhizoma Coptidis Formula Particle were developed.The validation results indicated that these methods were specific and reliable.2.2 Determination of paeoniflorin by HPLC A HPLC method of determination of paeoniflorin was developed and validated. The results showed good linearity(R2=0.9997) in the range of0.0805-0.5632 ug, the regression equation: Y = 6.0460x106 X + 6.087x103,r=0.9999. The average recovery of paeoniflorin was 99. 56% with RSD of2.74%.The content limit of paeoniflorin was determined by the average transfer rate of paeoniflorin to control the process of production and the quality of products.Conclusion: The process parameters of Rhizoma Coptidis Formula Particle were clear and preparation technology was reasonable, the quality could accurately perform the qualitative and quantitative analysis and effectively control the quality of product. |
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