Sinomenine Infiltration Pump Tablets

The alkaloid sinomenine(SM) extracted from the medicinal plant Sinomenium acutum Rehd. et Wils.which has been used in clinic for more for the treatmeat of various rheumatic diseases. In this paper, sinomenine hydrochloride was selected as the model drug to prepare the osmotic pump controlled release tablet. On the basis of the pre-formulation research about the properties of sinomenine hydrochloride , excipients and cellulose acetate (CA) free film, sucrose, polyvidone(PVP K30), citric acid was used as the substance of tablet core coated with cellulose acetate coating comprising with polyethylene glycol 6000(PEG6000) to make the sinomenine hydrochloride osmotic pump controlled release tablet. Pharmacokinetics in human of this formulation was studied.The intestinal absorption in vitro of rats for sinomenine hydrochloride was investigated. It was indicated that the absorption rate have no significant difference between duodenum, jejunum and ileum.The absorption rate in colon was slower than in other intestinal segment and significant.difference was observed. Thus, the intestinal absorption for sinomenine hydrochloride in rats had no specific absorption site.The properties of cellulose acetate free film such as adhesion, glass transition temperature and permeability for drug and water were evaluated to make help for formulation of coating film.In this paper, the factors of the variety and the amount of the osmotic pressure promoting agent, osmoplymers, the acid substance, handness of tablet core, the size of release orifice ,coating composition and the coating thickness effecting drug release from the osmotic pump tablet were studied.In order to find out the optimum tablet core and coating formulation, orthogonal experimental were adopted. The result indicated that the amount of polyvidone and citric acid ,the coating thickness ,the amount of plasticizer had significant influence on the drug release. As a result, the osmotic controlled release tablet for sinomenine hydrochloride was prepared and fitted to zero-order release kinetic using the osmotic pressure as the delivery force . The release rate from the tablet is insensitive to variations of the pH or rotation speeds of the paddle.The accelerating experiment showed that the drug release character , appearance and the content in well packaged did not change after six months store under 40 C,RH75% circumstance.Using the sustained release tablet on market as the reference, the pharmacokinetics in human of sinomenine hydrocholide osmotic pump controlled release tablet were studied. The result indicated that Tmax(11.5h)was longer, whereas Cmax(190.66ng/ml)was lower than products on market. The two formulation was similar in bioequality afer test. Obvious correlation was observed between absorption percentage in vivo and release rate in vitro.