Study On Release Mechanism In Vitro Of Sustained Release Preparation Of Modified Excipient â…¡

Objective To clarify release mechanism in vitro of sustained release preparation of modified excipient II, improving the quality of the evaluation system in vitro of sustained release preparation of the traditional Chinese medicine, which provided experimental evidences for research and development. Method Ephedrine, pseudoephedrine and scopolamine were used as index components to study release rate in vitro of sustained release tablets of modified excipient II with three different filler materials and sustained release tablets of HPMC by HPLC. The rate of erosion in the process of release in vitro were determined. The thickness and strength of gel layer were determined by stereo microscope and texture analyzer respectively. The underwater video was used to record the process of release in vitro of tablets. The particle size distribution and release in vitro were considered to study the variation of shedding particles. Meanwhile, the study combined with release rate in vitro to analysis release mechanism in vitro of sustained release preparation of modified excipient II from three stages comprehensively. Results ①Three stages were included in release processe of ephedrine, pseudoephedrine and scopolamine in those two types of sustained release tablets. Firstly, it was the quick-release phase(sustained release tablets of modified excipient II: 0 ~ 1h or 2h, sustained release tablets of HPMC: 0 ~ 2h). Secondly, it was the stationary phase(sustained release tablets of modified excipient II: 1 ~ 8h or 2 ~ 8h, sustained release tablets of HPMC: 2 ~ 8h). Thirdly, it was the slow-release phase(sustained release tablets of modified excipient II: 8 ~ 10 h or 12 h, sustained release tablets of HPMC: 8 ~ 12h). ②The sustained release tablets of both organic fillers and HPMC were in positive proportion with the rate of erosionbefore 10 h or 12 h. However, erosion occurred to sustained release tablets of both inorganic fillers and mixed fillers hardly. ③Three distinct regions(gel layer- wetting layer- glass core) were observed in sustained release tablets of both organic fillers and HPMC by stereo microscope. They formed gel layer before 0.05 h. The thickness of the gel layers grew rapidly at 0 ~ 2h, and they had small changes at 2 ~ 8h. ④Sustained release tablets of organic fillers had great gel strength before 2h, while its gel strength reduced fast(0.05h: 89.19g→2h: 20.33g). However, its gel strength remained within the range of 10.04 ~ 20.33 g at 2 ~ 8h. ⑤Underwater videos showed that when sustained release tablets of both modified excipient II and HPMC contacted with water, some particles fell down from the surface of tablets. The phenomenon of sustained release tablets of organic fillers was similar with the scatter of traditional pills. ⑥The shed particle sizes of sustained release tablets of modified excipient II went into the stable phase after 2h. However, particle sizes of sustained release tablets of HPMC grew along with the release time regularly. The maximum quantity of the shed particle of sustained release tablets of both modified excipient II and HPMC appeared at 6h. The proportion of three index components of shed particles in sustained-release tablets were: sustained release tablets of organic fillers > sustained release tablets of HPMC > sustained release tablets of mixed fillers > sustained release tablets of inorganic fillers. Conclusion Ephedrine, pseudoephedrine and scopolamine in sustained-release tablets of modified excipient II achieve balanced release by a new release mode(erosion- scatter- diffusion). Drug diffusion and matrix erosion act together in steady drug release phase, while drug diffusion and matrix erosion play a main role in rapid drug release phase and slow drug release phase respectively. And granulysin scattered on drug release plays a supporting role at the same time. In addition, it is speculated that the drug release through holes in sustained release tablets of both inorganic and mixed fillers. The study overcomes the single index component and single evaluation method in studying sustained release preparation of the traditional Chinese medicine of release mechanism in vitro, improving its quality of the evaluation system in vitro, which provids experimentalevidences for research and development.