The Research Of Atorvastatin Calcium Dispersible Tablets Prescription Optimization And Preparation Process

This topic was to slightly soluble drug Atorvastatin Calcium(Atorvastatin Calcium,ATORVASTATIN CA, referred to as "ATC") for the target drug, preparation of Atorvastatin Calcium dispersible tablets(ATC-DTs), with the disintegration time, hardness, stability of the drug, dissolution, etc as the indexes for prescription screening and optimization, did the disintegrating agent, filler, adhesive, etc prescription primary single factor experiment, and prescription was optimized by orthogonal design experiments on primary; Examined the influence of wet legal system grain of preparation process of the particle size and the relationship between the liquidity, drying temperature, water content of particles and environment relative humidity on preparations; Established pharmaceutical preparations of quality evaluation standard, did the stability of the high temperature, high humidity, illumination and so on. To determine the optimal prescription and preparation technology, through the three batch of pilot production,from the quality inspection, fully meet the quality requirements, to achieve the desired purpose. With the foreign patent was lifted its ban,this dispersible tablets provided the wet legal system grain of the prescription and preparation process, made up for the deficiency of domestic.The research contented includes:1. Set up the quality evaluation standard of pharmaceutical preparationsTo ensure accurate determination of drug content, ensure the quality of the preparation, the high performance liquid chromatography(HPLC) analysis method of the atorvastatin calcium had been established, the results showed that atorvastatin calcium in 5?g·m L-1~200 ?g·m L-1 concentration range, the detection of peak area and concentration gradient of the reference substance could show a good linear relationship,(r= 0.9999). Built the HPLC analysis method of ATC-DTs, and system adaptability of this method was good, high specificity, precision, recovery, repeatability conform to requirements. And established the ATC-DTs quality evaluation standards, such as: appearance, weight variation, disintegration time limit, disperse uniformity, dissolution and content uniformity, tablet brittle broken degrees, content determination and quality inspection standards and methods. Experiments showed that the HPLC method for the prescription screening, the establishment of the dissolution method, screening of preparationtechnology, quality and stability of the research provides accurate, sensitive and reliable basis, the detection method was suitable for ATC-DTs analysis testing and quality control.2. Screened the prescription and optimized the prescription and preparation processUsed the wet legal system grain of craft preparation of ATC-DTs. In order to research and prepare the ATC-DTs, at first, screened for the kinds of the disintegrating agent, filling agent, adhesive in the prescription.And after the screening, screened the dosage and the proportion of the other, the adding way of them. In addition, examined the characteristics of ATC, such as: angle of repose, compressibility and hygroscopicity. And the physical properties of the ATC-DTs particles, such as: the water content, angle of repose, critical relative humidity, the drying temperature and time on the preparation technology and environmental factors,etc as well. Finally,used the orthogonal design experiment optimize the prescription,and with the disintegration time limit, appearance, etc as indexes, screening the best prescription, got the optimal prescription of ATC-DTs.3.Screened the dissolution conditions of atorvastatin calcium dispersible tabletsDissolution conditions screening could ensure that the same preparation of different production batch products could have the same quality in vitro, also, made it for different patient could have the same bioequivalence. According to the dissolution rate of the data, mapped the dissolution curve, the release rate and degree of drug was reflected.In this article, through comparing and selecting the dissolution method,dissolution media, the speed of dissolution of ATC,to ensure the dissolution testing methods and testing time of ATC-DTs. On this basis, set up the dissolution conditions of ATC-DTs.4. Control the quality of atorvastatin calcium dispersible tabletsIn order to control the quality of ATC-DTs and improve the quality standard, did the experiments for quality evaluation. The research contented the ATC-DTs appearance, weight difference, disintegration time limit of inspection, disperse uniformity examination, determination of dissolution and content uniformity test and brittle broken degrees, and through quality evaluation, effectively controled the quality of dispersible tablets, ensured the quality stability,Also,the dispersible tablets quality standard was worked out. This research provided a reliable data and the reference to realize mass production and achieve the quality control in the process of production.5.Studied the influence of the content of calcium carbonate of atorvastatin calcium dispersible tablets on dissolution, stability and influencing factorsCalcium carbonate was a stabilizer in the prescription, on the basis of preliminary experiment and literature data, by adjusting the proportion of calcium carbonate in the optimal prescription; The main content and dissolution as indexes,through the stability test, judged the influence of the amount of calcium carbonate for stability; Test showed that atorvastatin calcium drugs under the condition of high temperature,high humidity and light,its content would be small reduced, added calcium carbonate could make it stably,but the amount of calcium carbonate had an impact on the quality of the preparation, a small amount of calcium carbonate made it less stable, if adding more could much preparation stability increased, but the dissolution of the drug was reduced, so it should control the amount of calcium carbonate which could not only guarantee the stability of the preparation and did not affect the drug dissolution.The significance of this study was to reform the prescription and process of ATC-DTs, made up the shortage for the powder direct tableting of listed product dispersible tablets.This paper adopted the method of traditional wet granule tablet, used calcium carbonate as a stabilizer, in addition to the sodium dodecyl sulfate(SDS), avoiding the SDS introducing toxicity, the preparation technology was of low cost,simple process, equipment, pharmaceutical enterprises generally all could produce. In addition, this thesis also did the system research for stability of calcium carbonate content in the ATC-DTs, and now, had yet to see this report, it had certain novelty.The purpose of this paper was to develop ATC-DTs with simple preparation process and stable quality.