Study On The Formulation, Process Optimization And Percutaneous Permeability Of Xiang-Jiang Transdermal Drug Delivery System

Object: A detection method of 6-gingerol in ginger was seted up to optimize the extraction condition of ginger oil by the supercritical CO₂ fluid extraction technology. A detection method of costunolide and dehydrocostuslactone in root of Aucklandia lappa was seted up to optimize the extraction condition of Aucklandia lappa by ethanol refluxing technology. Optimizing the prescription of traditional Chinese medicine for anti-Motion sickness(MS), and finding the best match of Rhizoma zingiberis recens,herba Pogostemonis,radix aucklandiae for anti-MS, and to prepare the anti-MS drug–Jiang-Xiang patch, optimizing its recipe and studying its percutaneous permeability in vitro.Methods: Setting up a detection method of 6-gingerol and comparing the three extraction technology of ginger: wet distillation, supercritical CO₂ extraction, ethanol percolate extraction. The extraction condition of ginger oil by supercritical CO₂ fluid were optimized using L9(3⁴) orthogonal table with extraction pressure, extraction temperature,pressure of separator I and extraction time as factors and with the yield of ginger oil and the level of 6-gingerol as index. Setting up a detection method of costunolide and dehydrocostuslactone, and an L9(3⁴) orthogonal test was used to evaluate the influence factors of extracting Aucklandia lappa by ethanol refluxing technology, including the concentration of ethanol, ratio of ethanol to drug material,extraction time and numbers, with the contents of costunolide and dehydrocostuslactone as index,then after ethanol evaporated to dryness the extract liquid under this best condition was abstracted by ethyl acetate for 3 times, and evaporated ethyl acetate to dryness to obtain the extract of Aucklandia lappa. The experiments were arranged by uniform design, MS index was taken as the parameters for MS in rodents in order to get the best proportion of the three extractive: Rhizoma zingiberis recens,herba Pogostemonis,radix aucklandiae ,which were extracted under the optimum extraction conditions. We prepared the Jiang-Xiang patch with the extractive of the best prescription, and optimized the recipe and researched its permeability characteristics with automatic instrument for permeability in vitro.Results: The yield of ginger oil was 2.117% and the level of 6-gingerol in the ginger oil was 23.164%(n=3) under the optimum technical condition of supercritical CO₂ extraction: extraction pressure at 20MPa;extraction temperature at 40℃;extraction time at 3h;pressure of separator I at 6MPa;pressure of separatorâ…¡at 3MPa. The optimum condition of Aucklandia lappa by ethanol refluxing extraction technology was 6 times of 80% ethanol,extracting 3 times and 1 hour each time.After abstracted by ethyl acetate and evaporating ethyl acetate to dryness, the yield of Aucklandia lappa extractive was 6.36%, the level of costunolide and dehydrocostuslactone in Aucklandia lappa extractive was 14.463%,18.567% (n=3). The extractive of prescription 2 is the best in prescription 1 to 5, and its action is better significantly than dimenhydrinate. The patches , the remedium cardinale of which was the extractive of prescription 2 were prepared with different extraction technology of ginger, different polyacrylic acid glue, and different ratio of penetration enhancer, the third recipe (supercritical CO₂ extractive, import polyacrylic acid glue and 1%azone) had the best permeability with a high transit through skin after two hours. Others showed a zero order release.Conclusion: The optimized extraction condition of ginger by the supercritical CO₂ fluid has the following merits: the biological activity maintained;high performance;pure extraction etc. The optimized extraction condition of Aucklandia lappa is the base of the preparation of percutaneous controlled-release drug delivery system by reducing the dose,improving the quality. MS index is a stable and sensitive parameters, it is suitable to evaluate anti-MS drugs, the optimum proportion of Rhizoma zingiberis recens , herba Pogostemonis , radix aucklandiae singled out by MS index can against MS efficiently and the patches made of the extractive of the optimum recipe as the remedium cardinale, have a good permeability through skin, it is a foundation for developing a patch which have a good perspective in anti-MS territory.