The Sinomenine Pulsatile Release Of The Film

Sinomenine Hydrochloride (SM), a pure alkaloid abstracted from traditional Chinese medicine-Caulis Sinomenii , has been mainly used for rheumatoid arthritis in clinical therapeutics .The objective of the study was to prepare and evaluate a pulsatile release tablets, using SM as model drug, which attempts to address clinically therapeutic requirements.In this study , UV spectrophotometry was developed for in vivo assay during the studies of release, content and physico-chemical properties. In the preformulation research, the physico-chemical properties of SM were investigated. The studies on solubility showed that the equilibrium solubility in distilled water , 0.1mol/LHCl aqueous solution ,pH6.8 phosphate buffer were 42.57,23.73 and 58.84mg/ml respectively. Solubility of SM decreased in high pH buffer, whereas appearant oil water partition increased. The compatibility of drug and exipients was assessed as well.Based on the comprehensive research on exipients, compressible starch, lactose and carboxymethyl starch sodium(CMS-Na)were used to make the tablet core. By the research of reciprocity and the tensile test, Eudragit RS100,Eudragit RL100 and Eudragit L100 were selected as the coating materials dissolved in alcohol at the level 4.0%(w/w, total solid applied), and triethyl citrate(TEC) was employed as the plasticizer at the level 15%(w/w). The coating formulation was optimized by orthogonal design, having the lag time and the pulsed-release time as the evaluation standard. The process factors affecting drug release were also investigated. The result of stability test showed that the pulsatile release tablets was unstable under high humidity condition, and wasstable when exposed to strong light, high temperature.Two parameters, time-lag(Tlag) and the pulsed-release time, were used to analyze release mechanism. By the test of water-uptake, the test of volume-swell, and the tensile test, we investigated the effect of the composition and thickness of the coating film on time-lag. The drug release confirmed to the model of lognormal distribution in 12h, and Ritger-Peppas equation was used to analyze the pulsed-release mechanism.The Gamma-scintigraphic trace evaluation demonstrated that the pulsatile tablets could disintegrate at ileum and release completely in colon. It would be reasonable and suitable for the pulsatile tablets with 5h lag time in vivo after oral administration.The plasma concentration of SM in dogs was determined by HPLC using enteric tablets as the reference. The Cmax,Tmaxand Tlag of the pulsatile release tablets were110.48ng/ml,7.04h and 3.778h respectively, and the pulsed-release time was 3.27h. The release of drug from the pulsatile release tablets of SM was shown to be in pulsed way in vivo, Its relative bioavailability was 94.23%. Good correlation existed between absorption percentage in vivo and release rate in vitro.