Hydrobromide High Black Armor Element Research Of Transdermal Drug Delivery Preparation

Lappaconitine Hydrobromide, an alkaloid series be extracted from aconitum sinomoutanum nakai, Ranunculaceae, Aconitum--hydrobromate lappaconitine, which was a first patent non-dependence analgesia drug in domestic. To be used in midrange pain and more. In addition, the drug also has been used in the local anesthetic, cooling, antipyretic and anti-inflammatory swelling. Because the fat-soluble and the water solubility of hydrobromide Lappaconitine was slightly, the therapeutic safety range of hydrobromide Lappaconitine was very narrow and the therapeutic index of hydrobromide Lappaconitine was low, the percataneous preparations of Lappaconitine hydrobromide will avoid the liver first pass effect of oral administration that avoid the drug be damage in the gastrointestinal tract, so it will reduce drug toxicity and adverse reactions, reduce delivery times, and convenient to use. There were being reported about the research of Lappaconitine Hydrobromide patches, but no reported about Lappaconitine hydrobromide transdermal microemulsion. In this study, the microemulsion and gels Prescription will be researched and the character of vitro percutaneous absorption of Lappaconitine hydrobromide transdermal microemulsion will be studied.In this study we first established an accurate, reliable in vitro analysis method and investigated the effect of various permeation enhancers on Lappaconitine hydrobromide percutaneous behavior. Through Study two transdermal factors of horny layer and concentration for Lappaconitine Hydrobromide. Testing its transdermal absorption performance through HPLC and TK-20B skin diffusion test instruments. Results was the Q(Accumulation osmolality) of the gommage at 24th hour is 13.22 times more than the Q of integrity skin; And the transdermal is not linear with the concentration of Lappaconitine Hydrobromide. So Reduce the Horny layer barrier can improve the transdermal of Lappaconitine Hydrobromide, reference for other similar study.Gel has the character of strong adhesiveness, Skin Absorption well after Topical Drug Administration. In this following study, the Lappaconitine hydrobromide gel will be prepared and compared four formulation of the Lappaconitine hydrobromide in 1% carbomer 934 groundmass and it with 1% Azone and 10%PG,3% LA,3% OA and 3% PG as enhancers, The experiment results showed that When used respectively, Azone+PG, OA+PG and 3% LA can enhance the cumulative permeation quantity, the Lappaconitine hydrobromide in 1% carbomer 934 groundmass with 3% LA shows the best penetration enhancing effect, which can significantly increase the permeability of Lappaconitine hydrobromide (P<0.01) and its enhancement factor was more than 3 times. The advantages of microemulsion for the dermal delivery of drugs will be showed below: First, the concentration of drug in the skin is increased due to large amount of drug can be incorporated in the formulation. On the other hand, the increased thermodynamic activity of the drug may favor its partitioning into the skin. At the same time, the ingredients of microemulsion may reduce the diffusional barrier of the stratum corneum and increase the permeation rate of drug via skin by acting as permeation enhancers. To further enhance the percutaneous permeability of Lappaconitine hydrobromide and improve the clinical efficacy, we prepared Lappaconitine hydrobromide microemulsion. The ability of Permeation in vitro and in vivo was evaluated.The basic components of microemulsion formulation were determined by investigating different oils, surfactants and cosurfactant.The pseudo-ternary phase diagram of microemulsion were made to determine the microemulsion area. And cumulative amount of Lappaconitine hydrobromide permeated through the rat skins per units area at 12 hours were selected as the response variables to optimize the microemulsion formulation. The optimal formulation was:Microemulsion with 5% Oleic acid、labrasol、Anhydrous alcohol and water has perfect transdermal absorption performance. Lappaconitine hydrobromide microemulsion has some profiles:the average particle size was 40.3±6.1nm,100%, with homogeneous distribution; the viscosity was 1.563Pa·s.Compared different concentrations of transdermal Lappaconitine hydrobromide microemulsion and the stratum corneum of the role of transdermal drug effects use vitro percutaneous absorption. The results show that when the hydrobromide Lappaconitine concentration from 2mg/mL to 4mg/mL, Lappaconitine Hydrobromide permeability coefficient with the concentration did not change significantly (P> 0.05), but the drug concentration increased from 4mg/mL to 8mg/mL change, Lappaconitine hydrobromide the permeability coefficient increases with the concentration increased significantly (P<0.05); microemulsion in the full amount of drug accumulation in the skin, exfoliate the skin with a significant difference (P<0.01).In the last part of this study, we evaluated the analgesic effect of lappaconitine hydrobromide microemulsion lappaconitine hydrobromide gel.The result was that in the method of hot plate, the pain threshold percentage of microemulsion group of within 4 hours was 124.5～224.6%, the pain threshold percentage of gel group was 18.9～37.8%. In the method of mice Writhing, the analgesia rate of microemulsion group was 87.5%, the analgesia rate of gel group was 37.5%, it shows that microemulsion group of within 4 hours was 124.5～224.6%, the pain threshold percentage of gel group was 18.9～37.8%. In the method of mice Writhing, the analgesia rate of microemulsion group was 87.5%, the analgesia rate of gel group was 37.5%, it shows that analgesic effect of the microemulsion group was better than the gel group.