A Novel Transdermal Delivery System For Antimalarial Artemisinin

The purpose of this study was to investigate a transdermal delivery system of antimalarial drug: artemisinin. The solubility of artemisinin was poor either in water or in oil. Saturated concentration of artemisinin in Duro-Tak 87-2677 (DT2677) pressure sensitive adhesive (PSA) was estimated approximately to be about 3% (w/w) without crystal within at least 1 year. To improve the concentration and the stability of the patch, PEG and Polyvinylpyrrolidone (PVP) were used as crystallization inhibitor.To improve the rate of percutaneous absorption of artemisinin, some penetration enhancers (PEs), including Glyceride, Transcutol(?), dimethylsulfoxide (DMSO), iso-Propyl Myristate (IPM) and etc, were considered to present synergistic effect. Transcutol(?), commonly as PEs, conduced to dissolving artemisinin and accelerating the cross-link of acrylic pressure sensitive adhesive containing carboxyl functional group with magnesium stearate. Glyceride presented predominant efficient to transdermal permeation of artemisinin, but it has irritation to the skin at high concentration. Propylene glycol (PG) and lecithin improved percutaneous flux of artemisinin across hairless mouse skin in vitro when associating with other PEs. When the content of lecithin exceeded 3% the cohesion of matrix was also declined and the breakdown phenomenon was found. The greatest cumulative amount permeated was obtained in patch with the synergistic combination of penetration enhancers (SCOPE) of glyceryl monooleate (GMO), Transcutol^?, DMSO, PG: 754.00±35.64 fig/cm2 until 24h. It could be concluded that glyceride together with other PEs and solvents synergistically enhanced the skin permeation of poorly soluble drug artemisinin in vitro.After transdermal administration in vivo, the mean maximal plasma concentration of artemisinin was 220 ng/ml at 2.5 h. The mean plasma concentration could be maintained over 100 ng/ml for at least 72 h, which was consistent with the result of in vitro substantially. After applying the patch to the nude mice infecting malaria for 96 h, 96.51% plasmodium turned darkening, which indicated that the development of transdermal artemisinin patch might be feasible.To improve the effect of PEs on the matrix of PSA and the preparation with high cohesion and appropriate adhesion, different metal ions were investigated. Magnesium stearate and magnesium chloride could make the matrix with -COOH cross linking, but sodium stearate did not have the effect. With high concentration of 1% magnesium stearate the speed of crosslinker was too swift to spead. 0.5% magnesium stearate was added to the patch to make the matrix cross linking, improve the cohesion.