Comparative Study Of The Quality Of The Two Skeleton System Sinomenine Sustained-release Tablets

This reserch closely followed the modern pharmaceutics, and did many singificant attempts in the application of a novel polymer excipient Polycarbophil Crosslinked with Chitosan (PCC) on the preparation of sustained or controlled release drug delivery system of Chinese material medica. In order to examine the performance of this new polymer on preparation of sustained or controlled release drug delivery system of Chinese material medica, we made sinomenine hydrochlorid which is extracted from a traditional anti-rheumatism chinense herb Qing Feng Teng as a model drug, and evaluated the quality of six kind of matrix tables(F1~F6) made of Hydroxylpropylmethylcellulose(HPMC) or Polycarbophil Crosslinked with Chitosan (PCC) about physical properties tests, in vitro drug release test and pharmacokinetics experiment.Firstly, we did the physical properties tests including thickness variation test, weight variation test, hardness test, friability test, the results of all these items met a criterion of the Pharmacopiea of People's Republic of China 2005. The thickness of the two kind of matrix-type tablets varied from 3.42 to 3.50mm and 3.62 to 3.66mm separately; the weight of different formulation varied from 74.7 to 81.5mg and 79.0 to 89.6mg separately, the weight variation of the same formulation is less than 7.5%.High performance liquid chromatography(HPLC) method for the quantitative determination of sinomenine hydrochlorid in the six kind of matrix tablets was established. Of all the formulations, the metered content varied from 19.14±0.32% to 20.09±0.11%(w/w), which was close to the designed content 20%. All the results above indicated that, the PCC matrix system was stable and controllable in quality, which was the same with HPMC matrix system.In the in vitro drug release test, the paddle method in Pharmacopiea of PRC 2005 was used. We selected phosphate-buffered saline(pH 7.4) as the medium and established the ultraviolet spectrophotometric method for the quantitative determinationof sinomenine hydrochlorid. The result indicated that the MDT of the PCC matrix system is longer than it of the HPMC system, which demonstrated that drug released slower in the PCC matrix system. Besides, according to the Ritger-pepper equation, diffusion and erosion were simultaneously exist in drug release mechanism of the PCC matrix system.In the pharmacokinetics experiment, we chose solid phase extraction(SPE) as the pre-disposal method of the plasma, and HPLC method for the quantitative determination of sinomenine hydrochlorid in plasma was established, sinomenine hydrochlorid in the plasma had a well linear correlation in a range of 50～2000ng/ml. Data processing of the blood drug level was done by DAS1.0, and the result indicated that F1 prepared by PCC polymer matrix had a longer half life period and peak time, and the blood drug level varied steady, PCC matrix exhibited a better ability in delayed drug release than HPMC.