Studies On Preparation And Pharmacokinetics Of Sinomenine Hydrochloride Controlled-release Pellets

Sinomenine hydrochloride is used in treatment of rheumatism and rheumatoid. In this paper, the identify of raw material, preparation of controlled-release pellets, quality standard, stability and bioavailbility were studied. The preclinical studies of sinomenine hydrochloride controlled-release preparation were finished. All the experimental results met Chinese pharmacopoeia (edition 2000) regulations.The material tested was identified as sinomenine hydrochloride according to a maximum absorption peak at 264 nm by ultraviolet scanning pattern, a molecular weight of 299 by mass spectrogram, positive identification reactions, and same Rf and color to reference by TLC.On the base of characteristics ultraviolet absorption of sinomenine hydrochloride, the ultraviolet spectrophotometry (UV) and reverse-phrase high performance liquid chromatography (RP-HPLC) methods were established for analysis of sinomenine. The linearity, specificity, repeatability and recovery met with the requirements of Chinese pharmacopoeia (edition 2000).By using membrane controlled-release technique and centrifugal coating pelletization, sinomenine hydrochloride controlled-release pellets were prepared. The first step is to prepare the core of pellets, The partical size distribution, plane critical angle, angle of repose, brittleness, hardness and moisture were used to evaluate the quality of the core of pellets. Eudragit NE30D was used to coating material. A self-designed minitype boiling fluiding bed equipment was used for screening of the coating prescription. The controlled-release efficacy were assessed according to drug dissolution rate. The equipment of centrifugal coating pelletization was used formagnifying production. The release of pellets were studied with different media, different release equipments and different speeds of revolution.Followed Chinese pharmacopoeia, the stability of sinomenine hydrochloride controlled-release pellets were studied. Influencing factors including high temperature, high humidity and strong light were investigated. Accelerated test and long-term test were conducted. Appearance of pellets, specific identification reactions, dissolutions and content determination were detected for the stability studies. The results showed that the coating membrane of pellets was sensitive to temperature and stable for other factors. In the bioavailbility experiment, the dogs were used as the experimental animals. Zheng qing feng tong ning tablets was used as the reference. Sinomenine in the biologic samples was analyzed by RP-HPLC. Parameters were estimated by 3P87 pharmacokinetics software. The results showed that the concentration-time curve of sinomenine was flatter, the duration was longer, peak and vale was less obvious than that of reference. Bioavailbility was equivalent. The present studies achieved our prospective aims.