Quality Analysis Of Nifedipine Sustained-Release And Controlled-Release Preparations

Nifedipine is a kind of calcium antagonist,which was developed by Bayer in 1969.It's used clinically to treat hypertension and angina pectoris.All the nifedipine sustained-release and controlled-release preparations made in China are generic drugs.The main differences between the generic and the original preparations could be observed in dissolution test and bioequivalence test.In this thesis,four kinds of dissolution media with different pH were used in dissolution test,the difference release curves indicated the difference preparation process of the generic and the original preparations.The particle size and the crystal form of API were analyzed and related to the rate of release.The main results of the study were as follows:1.The similarity research on release curves of generic and original preparationsThe similarity were calculated by f2 factor method,the results indicated that there are great differences between generic sustained-release preparations and original sustained-released preparations,while there are no significant differences between the generic controlled-released preparations and the original controlled-released preparations.2.The comparison of preparation process of the generic to that of the original preparationsThe results of comparative analysis on preparation process of the generic and theoriginal preparations showed that the rate of release was concerned in preparation technology.The original preparations were made by the API micronization technology,so the rates of release in four media are almost the same.Sodium alginate was used as sustained-release matrix in 4 kinds of generic sustained-release preparations,hydroxypropyl methyl fiber H-HPC was used as sustained-release matrix in 19 kinds of generic sustained-release preparations.Sodium alginate could form alginic acid precipitation under acidic conditions(pH?3),that is the reason of lower release in pH 1.2 dissolution medium than in three other media.And matrix formed by hydroxypropyl methyl fiber H-HPC would collapsed later in the dissolution test,it led to the faster release.The osmotic pump controlled-release preparation technology were used both in generic and original controlled-release preparations,so the rates of release of generic and original preparations in 4 media had no significant differences.3.Hardness detection of generic sustained-release tabletsThe correlated research between hardness of generic sustained-release tablets(without coating)and the rate of release indicated that the release was concerned in hardness.The hardness of different batches varied,that resulted in the varied rates of release.4.The study on particle size,crystal form of nifedipine APIThe crystal form of 5 samples from different manufactures was analyzed by IR,DSC,Raman and X-ray diffraction.The API particle size was also detected.The results showed that the crystal form of 5 samples was the same,but the appearance of the crystal and the particle size were different.5.NIR and Raman studies on nifedipine API and preparationsNIR and Raman models had been set up.NIR models could be used in quickly identification and quantitative analysis of nifedipine sustained-release preparations.Raman models could be used in quickly identifying counterfeit products.