湿法制粒片剂生产过程综合控制系统应用研究

发布时间：2018-06-25 02:08

本文选题：湿法制粒 + BP神经网络　；参考：《兰州理工大学》2017年硕士论文

【摘要】：湿法制粒片剂生产过程主要包括湿法制粒、干燥、压片、包衣四个工段,其各个生产工段之间环环相扣,上一工段的好坏严重制约下一工段的生产并最终影响片剂产品的质量。伴随着新技术的层出不穷以及GMP(Good Manufacturing Practice)规范在湿法制粒片剂生产管理中的实施,传统的控制要求、控制方法和片剂生产落后的管理模式已不能满足湿法制粒片剂生产的发展需求。因此需要研究设计湿法制粒片剂生产的综合控制系统,以适应现代化生产的要求。本文以浙江温州某制药设备生产公司的湿法制粒片剂生产线为研究对象,在深入了解片剂生产工艺、方法、生产需求的基础上,针对生产过程中存在的一系列问题系统地研究了湿法制粒阶段的粒径大小优化、沸腾干燥机流化仓内部温度控制以及湿法制粒片剂生产过程信息化、网络化、集成化技术设计。论文的主要工作如下:1)为了提高湿法制粒所得药物片剂的质量,必须严格控制湿法制粒机出料口颗粒的平均粒度。文中根据湿法制粒机输入输出变量关系构建合理的BP神经网络,用来拟合平均粒度大小与搅拌桨转速、切割刀转速、搅拌时间、切割时间非线性函数关系。此外,为避免BP神经网络由于初始权值、阈值的随机选取而导致的易陷入局部极值点而得不到全局最优解的缺点,利用遗传算法优化构建好的BP神经网络,从而实现对平均粒径大小与其影响因素的非线性拟合,实现对粒径的良好控制,提高片剂生产的质量。2)针对沸腾干燥机的流化仓内温度控制精度问题,本文以沸腾干燥机的蒸汽热交换器为研究对象,对该工段的工艺和传热过程进行机理分析,建立其简化模型。针对沸腾干燥机温度控制的非线性、纯滞后、时变性的特点,设计自适应模糊PID控制器并进行Matlab/Simulink系统仿真。最终结果表明在自适应模糊PID控制下,不仅响应速度快,无稳态误差,而且超调量较少。3)研究设计片剂生产过程的综合自动化控制系统,实现对湿法制粒片剂生产各个工段的集中监控和分散控制。既解决湿法制粒片剂生产过程中对单台设备的特殊控制要求,又实现系统的分布式控制和远程监控功能,提高生产过程的自动化程度。实现湿法制粒片剂生产过程的网络化、集散化和智能化控制。
[Abstract]:The production process of wet granulation tablet mainly includes four sections: wet granulation, drying, pressing and coating. The production of each section is interlocked with each other. The quality of the next section is seriously restricted by the quality of the previous section and ultimately affects the quality of the tablet product. With the emergence of new technologies and the implementation of good Manufacturing practice (GMP) in the production and management of wet granulation tablets, the traditional control requirements, control methods and the backward management mode of tablet production can no longer meet the development needs of the production of wet granulation tablets. Therefore, it is necessary to design a comprehensive control system for the production of wet granulation tablets to meet the requirements of modern production. This paper takes the wet granulation tablet production line of a pharmaceutical equipment production company in Wenzhou, Zhejiang Province as the research object, on the basis of deeply understanding the production technology, method and production demand of the tablet. Aiming at a series of problems existing in the production process, the optimization of particle size in wet granulation stage, the internal temperature control of fluidized chamber of boiling dryer and the information, network and integrated technology design of wet granulation tablet production process were studied systematically. The main work of this paper is as follows: (1) in order to improve the quality of the tablets obtained by wet granulation, it is necessary to strictly control the average particle size at the outlet of the wet granulator. According to the relationship between input and output variables of wet granulator, a reasonable BP neural network is constructed, which is used to fit the nonlinear function relationship between the average particle size and the rotating speed of the agitator, the cutting cutter speed, the stirring time and the cutting time. In addition, in order to avoid the disadvantage that BP neural network is easy to fall into local extremum and get global optimal solution due to the initial weight and random selection of threshold, genetic algorithm is used to optimize the BP neural network. Thus the nonlinear fitting of the average particle size and its influencing factors, the good control of the particle size and the improvement of the quality of the tablet production are realized.) the temperature control accuracy in the fluidized chamber of the boiling dryer is solved. In this paper, the steam heat exchanger of boiling dryer is studied. The mechanism of process and heat transfer in this section is analyzed, and the simplified model is established. In view of the nonlinear, pure lag and time-varying characteristics of boiling dryer temperature control, an adaptive fuzzy pid controller is designed and simulated by Matlab / Simulink system. The results show that under the adaptive fuzzy pid control, not only the response speed is fast, no steady error, but also the overshoot is less. 3) the integrated automatic control system for tablet production process is designed and designed. To realize the centralized monitoring and decentralized control of each stage of wet granulation tablet production. It not only solves the special control requirements of single equipment in the process of wet granulation tablet production, but also realizes the distributed control and remote monitoring function of the system, and improves the automation degree of the production process. To realize the networked, distributed and intelligent control of the production process of wet granulation tablets.
【学位授予单位】：兰州理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ460.5;TP273

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