Preparation Of Piroxicam-β-cyclodextrin Inclusion Compound And Its Capsule

Piroxicam is Non-steroid Anti-inflammatory Drug. It is mainly utilized in the treatment of patients with rheumatoid arthritis,its half life is long (t1/2 as long as 36～45h ),and has few adverse reactions. But for its hydrophobicity,its dissolution and absorption is effected in stomach and intestines. In other words,the character leads to a low bioavailability and inferior curative effect.The object was to study the preparation process of piroxicam-β-cyclodextrin inclusion compound. Various parameters influencing the quality of piroxicam have been discussed. At last,piroxicam-β-cyclodextrin inclusion compounds were prepared by freeze-drying. The inclusion rate was used as the criteria of selecting optimal conditions,which were molecular ratio of piroxicam toβ-CD,weight ratio of piroxicam to ammonia,mixing temperature and time. The best preparation process was established by analyzing the result of orthogonal test. The best prescription were: molecular ratio of piroxicam toβ-CD was 1:2.5;weight ratio of piroxicam to ammonia was 1:0.5;mixing temperature was 70℃and mixing time was 0.5h.The formation of the inclusion was proved by Differential Scanning calorimeters,IR,X-ray diffractometry and solubility before and after including. The result of DSC indicated that inβ-CD inclusion compounds,piroxicam existed as an amorphous form andβ-CD inclusion compounds can increase the dissolution rate of piroxicam significantly.For the purpose of making piroxicam-β-CD inclusion compounds into capsules, we did comprehensive research in the moistening agents,optimizing of technique and pharmaceutical characteristics. The capsules release model of piroxicam-β-CD inclusion compounds was in keeping with Weibull distribution.According to the related requests of the appendices of Chinese pharmacopoeia (2005 edition,Ⅱpart), we performed the quality analysis to the capsules of piroxicam-β-CD inclusion compounds including their characters,identification,inspection,quantification, etc. we used HPLC method to perform quantification, which was able to determie the content of the sample accurately and precisely after the groping chromatography condition and studying of methodology. Then ,we established the quality standard of the capsules of piroxicam-β-CD inclusion compounds. According to this quality standard, we performed quality inspection to the three blocks of medium amplified preparations. The results of three blocks of medium amplified preparations accorded with the related regulate.We investigated the stability of the three blocks medium amplified preparations, including stressing testing (illumination,high temperature and high moisture),accelerated testing,long-term testing. The results of stressing testing showed the capsules are stable under illumination,high temperature and high moisture. The results of accelerated testing and long-term testing showed that the capsules keeped stability.