| Objective: Asiaticoside is a odorless, tasteless white crystal have cited moist, chemical name: 2-alpha,3-beta,23-trihydroxy-urs-12-en-28-oic aci o-6-deoxy-alpha-l-mannopy;ranosyl-(1-4)-o-beta-d-glucopyranosyl-(1-6)-o-beta-d-glucopyranosyl ester.Formula: C48H78O19. Molecular Weight: 959.12. Asiaticoside inhibit fibroblast proliferation, anti-tumor, anti-inflammatory pharmacology cardiovascular protection. Now widely used clinically to inhibit the proliferation of fibroblasts to achieve the treatment of burn scars and scleroderma and other fibrotic diseases. It is mainly through the activation of epithelial tissue so that the wounds to accelerate healing, inhibition of collagen synthesis, so that excessive proliferation of connective tissue matrix and fiber components are controlled and play a role in the treatment of scars. Asiaticoside commonly used in the treatment of burn scars and scleroderma and other fibrotic diseases. Because Asiaticoside is a weak acid and too large molecular weight compounds, very slightly soluble in water, and the drug solubility in water, direct impact on transdermal drug absorption, resulting in a lower bioavailability of the drug to clinical application subject to certain restrictions. Given Asiaticoside in clinical application problems in this study the use of non-ionic surfactant and cholesterol as a highly biocompatible materials, preparation Asiaticoside non-ionic surfactant niosomes, in order to improve the transdermal absorption rate, reduce irritation and increase drug stability, improve patient medication compliance, and lay the foundation for the development of new Asiaticoside transdermal preparation.Methods: High performance liquid chromatography(HPLC) method for the determination Asiaticoside concentration, linear intra-day precision, recoveries and stability test method validation. Separating equilibrium dialysis free Asiaticoside and then to niosomes, measured niosome encapsulation efficiency and drug loading. Adoption film hydration were prepared by evaporation method Asiaticoside niosome encapsulation efficiency and drug loading as an indicator of the type and amount of surfactant, the dosage of the drug, the drug fat ratio, incubation time, incubation temperature and speed of the rotary evaporator and other prescription factors and process conditions single factor screening and then a larger factors were orthogonal design prescription optimize the preparation process, determine asiaticoside niosomes optimal formulation and process and verify it.The optimal prescription Asiaticoside niosomes rational choice based on the solubility of the release medium, using Franze transdermal diffusion instrument investigate Asiaticoside niosomes in vitro release behavior and draw the cumulative release rate time curve for zero order release of the data, first order, Higuchi and Ritger-Peppas release model fitting and model fitting, explore the mechanism of drug release from the niosomes. Study temperature and light conditions on Asiaticoside niosomes nature and long-term stability under storage conditions of the past, to provide a theoretical basis for determining its storage conditions.The influence percutaneous absorption of Asiaticoside was evaluated using the retention time Asiaticoside niosomes and Azone, menthol, borneol three common penetration enhancers when used alone.Investigate factors influence the impact of temperature, light, etc. for Asiaticoside niosome stability and long-term stability under storage conditions of the past, to determine the conditions of storage niosomes provide a theoretical basis.Results: Asiaticoside standard curve equation is: A=2287.7C-3934.5,(r=1, n=5), indicates that the concentration of Asiaticoside 26.65μg?ml-1~426.4μg?ml-1 within the range good linear relationship. Low, medium and high concentrations of asiaticoside day precision RSD were 1.39%, 4.08%, 2.05%(n=5); day precision RSD were 3.55%, 1.83%, 0.47%. The average recovery was 105.60%, 24 h peak area RSD is 0.04%, the lowest detectable concentration Asiaticoside of 0.5μg?ml-1. Equilibrium dialysis method can effectively separate niosomes and free drugs to meet the requirements of the niosome encapsulation efficiency. Univariate study results show that for Asiaticoside niosome encapsulation efficiency greater impact on three factors were surfactant and cholesterol ratio(w/w), incubation temperature and incubation time, after optimization to determine the optimal prescription for: asiaticoside dosage of 36 mg + lipids(feed ratio of 100:25, m/m) + incubation temperature 30℃ + incubation time 30 min. Was prepared according to the optimal prescription Asiaticoside niosome encapsulation efficiency and drug loading was 89.56% and 25.26% respectively, the morphology of the double circular hollow sphere.In vitro studies showed that transdermal Asiaticoside solution 24 h through lower cumulative amount of 3.73μg?ml-1, Asiaticoside niosomes release the most liquid in the receiver, 24 h through cumulative amount 25.15μg?ml-1, the cumulative penetration percentage reached 88.95%, penetration of the drug effect was significantly higher penetration enhancers groups. In vitro percutaneous penetration curve basic Higuchi equation.The results show that the influence of temperature and light on the stability Asiaticoside larger niosomes, long-term stability tests showed, 4 ℃ under dark sealed six months, Asiaticoside niosome encapsulation efficiency decreased a slight flocculation.Conclusion: This study established method for the determination of Asiaticoside, in line with the requirements of resolution, high precision, good stability, and accurate. Using niosomes roundness film evaporation prepared well, and the process has been optimized for high prescription drug niosome encapsulation efficiency and drug loading volume. Vitro percutaneous experiment, so Asiaticoside niosomes with good permeability. Drug-loaded niosomes isolated dark at 4 ℃ under oxygen conditions of preservation, good stability. |
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