| Objective:Gout is a chronic metabolic disease caused by the disorder of purine metabolism in the body.Acute gouty arthritis is one of the common orthopedic illness which is the inflammatory reaction of pathological damage caused by the urate deposition in the joint capsule, bursa, cartilage, boneand and other tissues. In the21st century, accompanied by of the continuous improvement of people’s living standards and the structure changes of diet, the incidence of acute gouty arthritis showes a gradual increase in a trend, and thus pose a serious threat to people’s health and quality of life. In the domestic and international clinical treatment for the disease, the main treatment is to take advantage of various drugs for anti-inflammatory, relieving pain, decreasing urate deposition in the blood and so on. Between these drugs, colchicine has a good effect on the treatment of acute gout. However, colchicine mainly through the oral administration, and has more adverse effects, and thus to some extent, they impact the clinical comprehensive applications of the drug. The purpose of this study is to prepare colchicine ethosomes, to design the preparation of its pressure-sensitive adhesive patches, and investigate the feasibility and quality of preparation of the patch in transdermal drug delivery systems.Method:By the uniform design sotfware, the uniform design was used to optimize the patch components of polyacrylic resin Ⅳ#,succinic acid and triethyl citrate,with its initial adhesion and hold tack as the composite indice.Then the colchicine ethosomes patches of soybean lecithin(SL) and hydrogenated soybean phosphatidylcholine(HSPC) were prepared.The automated dissolution test analyzer and improved Franz diffusion cell were adopted to compare the release and transdermal properties of the two types of colchicine ethosomes patches respectively.Moreover, they were studied by their stability of the preparation of light, humidity and high temperature conditions, and a rabbit skin irritation test and in vivo drug kinetics study. The colchicine dynamic changes were investigated for the patches in mice.Result:The viscosity requirements of colchicine ethosomes patches were in line with the provisions of the2010edition of Chinese Pharmacopoeia. The vitro release of the colchicine ordinary patches, the ethosomes patches of SL and HSPC fitted to the Higuchi equation.Their transdermal absorption fitted to the zero level quation, and their transdermal rates of J were improved in turn. The stability of the ethosome patches of HSPC was higher than SL, especially for colours. The ethosome patches of SL and HSPC had no stimulation for48h by the rabbit skin irritation test.Compared with the oral administration, two colchicine ethosome transdermal patches had various differences that their Tmax and mean retention time MRTX were extended (p<0.05), peak plasma concentration Cmax was decreased (p<0.05), and AUC was significantly higher (p<0.05).And the HSPC Colchicine ethosome patches had the higher AUC than the SL Colchicine ethosome patches.Conclusion:Compared with ordinary patches, the two ethosomes patches have high in vitro cumulative release rate of Q and transdermal rate J.It indicates that ethosomes can have the role of improving transdermal drug absorption. And the stability test of the HSPC.patches,especially for color change, and in vivo drug parameters such as AUC, Cmax, and so on in mice are superior to the SL ones. So HSPC is a novel kind of excellent phospholipid material that can replace SL, and that can improve the stability and the drug absorption rate of ethosomes in the body. |
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