Design And Evaluation Of Sinomenium Drug In Adhesive Patches

Sinomenine is a principal alkaloid isolated from the stem and root of Chinese medical plant Sinomenium acutum. Due to its analgesic and anti-inflammatory effects, sinomenine has been utilized clinically to treat rheumatoid arthritis and neuralgia. However, because of its short half-life, large dosage and long course of treatment, some severe adverse reaction often occurred during the therapy process, such as erythra and gastronintestinal irritation. In order to reduce the adverse effects after oral administration, the once daily sinomenine patch was formulated and evaluated in vitro.Based on the theory that the formation of ion pairing can enhance the permeability of drug, sinomenium （SM） was first prepared from sinomenium chloridate （SM-C1）, The formation of SM was demonstrated by differential scanning calorimetry （DSC） thermogram studies. Promoting effects of counter ions and enhancers on the penetration of SM was evaluated from the EI system （ethanol:isopropyl myristate （v/v）=2:8） through excised rat skin using 2-compartment horizontal diffusion cells. As counter ions, maleic acid, fumaric acid, succinic acid and lactic acid were used. The steady-state flux of SM markedly increased in the presence of lactic acid. In addition, N-methyl-2-pyrrolidone, azone, menthol and oleic acid were employed as penetration enhancers, however, only azone and menthol increased the flux of SM in comparison to the control, menthol had the highest enhancing activity. Than, the promoting activity of menthol in combination with azone or in combination with lactic acid on 1he permeation of SM were also evaluated, but no synergistic effect was observed.Drug-in adhesive patches of SM was prepared using DURO-TAK?87-4098 by the organic solvent evaporation technique. In vitro permeability of SM from patches was also evaluated through excised rat skin using 2-compartment horizontal diffusion cells. The optima formulation of SM patch was determined to be 1.0% （w/w） SM and 10% isopropyl myristate （w/w）. Comparing the permeation parameters of drug from patches prepared by the DURO-TAK^?87-2677 and DURO-TAK^?87-4098, the type of pressure sensitive adhesives affected the permeability of drug significantly. Although the steady-state flux of drug from patches was much lower than that from the EI system, the permeation characteristics of drug from the two were similar. Therefore, the investigation on the permeation of drug from the EI system was a very useful method of pre-formulation study for patches.Adhesion （tacking strength, cohesive strength and peeling strength）, drug content and drug releasing degree were also investigated in the present study. Based on the experiment results, the specific requirements of the indices were instituted.