Research On Preparing Sustained-Release Pellets Of Two Different Kinds Of Drugs In Different Doses

This thesis is to report that sustained-release pellets with well sustained-release effect were successfully prepared by domestic extrusion-spheronization machine and small-scale fluid-bed coater and using high-dose drug Metformin Hydrochloride(MH) and low-dose drug Aspirin(ASP)as model drug and Eudragit?NE30D as coating material, so that this work has referential value for R&D and quality controll of oral sustained-release and controlled-release pharmaceuticals in China.There are certain difficulties in preparing the high-dose MH sustained-release pellets, in which one is that the pellet core has to contain high drug content and the other is that the coating membrane thickness has to be suitable to ensure an expectable effect. The orthogonal design to optimize the best technological process was adopted and the most desirable formulation was determined based on single-factor study. On the basis of the previous work, pellet cores with high drug content (60%) were prepared by "properly" adding small amount of moistening agent in the spinning spheronizer which has further improved the pellets' sphericity andproductivity. By studying on the technological and formulational factors that effect the release behavior of coated pellets, the best coating process and formulation were determined. The desirable MH capsule providing a clear sustained-release effect was obtained by mixing two kinds of coated pellets having different release rate in proper proportion. Also, quality evaluation and stability tests of the preparation were done, and at last drug release mechanism was discussed.In the process of making low-dose ASP pellets, ASP was unstable and easy to resolve. The best technology and formulation were optimized in making pellet cores through the study of effecting factors that might be concerned and as a result, the problem of ASP's unstability has been solved to a certain extent. Coated pellets with promising sustained-release properties have been successfully prepared by the optimization of both coating process and coating formulation and also through the selection of coating membrane thickness and amount of pore former. Also, quality evaluation and stability tests of the preparation were done, and drug release mechanism was discussed. The pharmacokinetics results in-vivo from experimental dogs showed that self-made sustained-release capsule has an obvious sustained-release character in comparison with the conventional-tablet on market and the co-relationship between the absorption in-vivo and the dissolution in-vitro is significant.