The Sinomenine Flexible Liposomes And Evaluation

Sinomenine Hydrochloride(SM), a pure alkaloid abstracted from traditional Chinese medicine-Caulis Sinomenii, has been mainly used for rheumatoid arthritis in clinical therapeutics. However, oral administration of SM sometimes leads to the side effect of gastrointestinal complaints (e.g. nausea, diarrhea, constipation, gastralgia and occasionally vomiting). Thus, the Transdermal Drug Delivery System (TDDS) is expected. SM transfersome which is flexible and deformable was prepared and evaluated in this thesis. It can delivery more drugs into local deeper tissues and avoid high plasma concentration. It is important to minimize the side effects of oral SM and increase curative effect.Firstly, the method of UV spectrophotometry was established, and some physicochemical properties were determined. Such as equilibrium solubility, Oil/Water partition coefficient, the stability in solution, and the effect of pH on them etc.In the study, Sephadex gel column chromatography and mini-column centrifugation method which separated SM from transfersome were compared. The effluent behavior of drug's PBS solution and blank transfersome on the Chromatographic column and mini-column of Sephadex G-50 was investigated. The concentration of SM in transfersome was determined by HPLC method. The advantage and disadvantage of two methods were compared and mini-column centrifugation was selected for determining the entrapment efficiency (EE) of SM transfersome in final.Reverse phase evaporation method and pH gradient method were used for preparing SM transfersome. The former method investigated the effect of the ratio of PC and sodium cholate, the volume ratio of organic phase and aqueous phase and pH of PBS solution on the entrapment efficiency of SM transfersome, and the latter method studied the effect of the ratio of PC and sodium cholate, the ratio of drug and PC, incubation temperature and pH of external water phase on the entrapment efficiency of SM transfersome. Orthogonal experimental designs were respectively applied to optimize formulation for SM transfersomes prepared by two methods, and two optimal preparations have entrapment efficiency of 52.9±0.3% and 52.7±0.4% respectively. The evaluation on different transfersomes prepared by two methods was given from appearance, shape, particle size distribution, deformity, stability and so on. The preparation prepared by reverse phase evaporation method was used for transdermal delivery test.The transdermal delivery of SM transfersome across rat skin was studied by amended Franz diffusion cells in vitro. The results showed that comparing to occlusive donor compartment, penetration of SM into skin was higher in nonocclusive situations. Transfersome was deformable which is attributing to sodium cholate. The cumulative amount of SM increased with the increasi ng sodium cholate when it was no more than 100 mg. The bilayer structure of transfersome was necessary to promote the permeation of SM. Sodium cholate was substituted by equal dose of tween80 and span80, the order of the cumulative amount of SM was sodium cholate>tween80> span80, which suggested that sodium cholate can enhance transdermal delivery of SM.In addition, the irritancy of SM transfersome on skin and the pharmacodynamics were studied. The results of experiment proved that SM transfersome had no irritancy on skin, but excellent anti-inflammatory and analgesic effects.