Research On High Sensitivity Quality Inspection Method For Solid Formulation Feeding System

With the rapid development of pharmaceutical technology,the production model of solid dosage forms intends to shift from batch to continuous manufacturing.The development of Process Analytical Technologies(PAT)is the basis for the approved application of continuous manufacturing.Among the monitoring parameters of PAT,the detection of the amount(quality)of drug ingredients is particularly important because the accurate control of the content of active ingredients in the production process is directly related to the most important performance indicators of drugs such as safety and efficacy,while the content of active ingredients(API)of drugs is relatively small,which requires the accurate and efficient detection and control of the tiny quality of various ingredients in the pharmaceutical production process.In order to solve the problem of online real-time detection of active ingredients in the production process of solid formulations,the thesis proposes a preloaded bias current compensation method based on piezoelectric sensors and designs a micro-mass detection system with high sensitivity and high accuracy based on this method,which can realize dynamic measurement of micro-masses.The main contents of the paper are as follows.(1)Study the micromechanisms of the piezoelectric effect of piezoelectric ceramics and piezoelectric quartz,and analyze the advantages and disadvantages of the two piezoelectric materials as sensitive elements to provide a theoretical basis for the selection of the sensor of the measurement system and the design of the detection circuit.(2)Analyze the calculation method of particle agent falling impulse,establish the structural model of impact type measurement of particle mass,and design the measurement system.(3)Based on the characteristics of piezoelectric effect and charge amplifier,propose and study a preload bias current compensation method to achieve the goal of reducing the threshold of charge amplifier and improving the measurement accuracy.(4)A quasi-static amplifier circuit is designed to reduce the charge leakage rate by means of theory and simulation software.High-accuracy detection of tiny and low-frequency quantities using piezoelectric sensors was achieved.(5)The performance of the micro mass detection system was tested.Data acquisition was carried out by software using a data acquisition card from NI.And the linearity and stability analysis,sensitivity comparison experiment and calibration experiment were conducted for the micro mass detection system.The experimental results show that the micro mass detection system designed in this paper can accurately measure the micro mass particles on-line.The minimum measurement value is 1.5mg,the sensitivity is 1.077mv/mg,the stability is good,and the linearity is high;It is proved that the preload bias current compensation method proposed in this paper can effectively improve the measurement sensitivity and resolution.