Preparation And Pharmacokinetics Of Breviscapine Sustained - Release Tablets

Breviscapine is the flavonoid extracted from Erigeronb reviscapine(vant) Hand Mass., having remarkable effect on cardiovascular diseases. Breviscapine with short half-life and low bioavailability was selected as the model drug.to prepare breviscapine sustained release tablets (DZHS SRT) with HPMC as matrix material, which was designed to be administrated once a day.A comprehensive study on the DZHS SRT was carried out. The main contents were as follows:1 PreformulationAn UV spectrophotometry method was developed for the determination of the assaying of breviscapine and drug release from tablets, and also determined the solubility of breviscapine in various media. The method was quick and accurate, which could meet the requirement of the analysis.2 Study on the formulationSingle factor tests were carried out and it was found that the amount of HPMC and NaHCO3 and the concentration of PVP had great effects on drug release. Based on the results of single factor tests, orthogonal experiment with three factors and three levels was designed to optimize the formulation for DZHS SRTQuality assessment on the self-prepared DZHS SRT was carried out. The result showed that the homogeneity of one batch and the repeatability of three batches were good. Compared with the DZHS tablet, the SRT had a better sustained release effect. Stress condition test showed the release behavior of DZHS SRT was fairly effected by high humidity and should be preserved sealed.The drug release mechanism was discussed, which was the combination of hydrophilic gel erosion and diffusion.The stability of DZHS SRT was studied for nine months. The results indicated that the factors of characteristics, content and in vitro release remained unchanged. It was showed that the self-prepared DZHS SRT was stable. 3 Pharmacokinetics studyWith the commercial DZHS tablets as the reference, the pharmacokinetics study of self-prepared DZHS SRT was performed in twelve dogs. An HPLC method was employed to detect the plasma drug concentration of dogs. The pharmacokinetic parameters of the test and reference tablets were as below: AUC were 37.8±17.7 and 13.0±6.5 (μg/ml)h, Tmax were 3.75±1.06h and 1.92±0.63h, Cmax were 2.70±0.92μg/ml and 3.48±1.36μg/ml. The relative bioavailability was 100.2±18.3%, and the two formulations were bioequivalent. Compared with the reference preparation, breviscapine Sustained-release tablets had the characteristic of sustained-release. The results indicated that DZHS SRT had good vivo-vitro correlativity.