不同混合溶剂对丹参酮Ⅱ_A-PLGA微球的影响
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摘要
目的考察不同混合溶剂(二氯甲烷-二氧六环、二氯甲烷-乙酸乙酯、二氯甲烷-丙酮、二氯甲烷-乙腈)对丹参酮Ⅱ_A-PLGA微球的影响。方法乳化-溶剂挥发法制备微球后,测定其载药量、包封率、粒径、体外释放度、药物分布参数,分析微球性能与溶剂性质的相关性。结果所得微球平均载药量约10%,包封率约90%,粒径约40μm。不同混合溶剂中微球体外释放行为、药物分布存在明显差异,相关性显著。结论混合溶剂对丹参酮Ⅱ_A-PLGA微球性能和药物分布有较大影响。
AIM To investigate the effects of different solvent mixtures( dichloromethane-dioxane,dichloromethane-ethyl acetate,dichloromethane-acetone,dichloromethane-acetonitrile) on tanshinone Ⅱ_A-loaded PLGA microspheres. METHODS Emulsion-solvent evaporation method was applied to preparing microspheres,after which their drug loading,encapsulation efficiency,particle size,in vitro release and drug distribution parameters were determined, along with the correlation analysis of microsphere performance and solvent properties.RESULTS The obtained microspheres demonstrated the average drug loading of about 10%,encapsulation efficiency of about 90%,and particle size of about 40 μm. Obvious differences existed in the microspheres' in vitro release behaviors and drug distributions in different solvent mixtures, together with significant correlations.CONCLUSION Solvent mixtures have great effects on the performance and drug distributions of tanshinoneⅡ_Aloaded PLGA microspheres.
AIM To investigate the effects of different solvent mixtures( dichloromethane-dioxane,dichloromethane-ethyl acetate,dichloromethane-acetone,dichloromethane-acetonitrile) on tanshinone Ⅱ_A-loaded PLGA microspheres. METHODS Emulsion-solvent evaporation method was applied to preparing microspheres,after which their drug loading,encapsulation efficiency,particle size,in vitro release and drug distribution parameters were determined, along with the correlation analysis of microsphere performance and solvent properties.RESULTS The obtained microspheres demonstrated the average drug loading of about 10%,encapsulation efficiency of about 90%,and particle size of about 40 μm. Obvious differences existed in the microspheres' in vitro release behaviors and drug distributions in different solvent mixtures, together with significant correlations.CONCLUSION Solvent mixtures have great effects on the performance and drug distributions of tanshinoneⅡ_Aloaded PLGA microspheres.
引文
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[2]朱娅芳,姜丰,吴朝花,等.丹参酮ⅡA微球的研制与药剂学性质表征[J].中药材,2016,39(1):138-142.
[3]刘梅,夏鑫华.丹参酮ⅡA的化学稳定性研究[J].中药材,2010,33(4):606-609.
[4]董川,乔锦丽,杨频. pH对隐丹参酮和丹参酮A的荧光特性及分子结构影响研究[J].光谱实验室,2000,17(4):369-372.
[5]朱娅芳.丹参酮ⅡA微球的制备及药剂学性能研究[D].贵阳:贵州医科大学,2016.
[6] Sah H. Ethyl formate-alternative dispersed solvent useful in preparing PLGA microspheres[J]. Int J Pharm,2000,195(1-2):103-113.
[7]孙美丽,班俊峰,黄思玉,等. PLGA微球载药量和包封率的影响因素及控制[J].广东药学院学报,2011,27(6):643-648.
[8] Luciani A,Guarino V,Ambrosio L,et al. Solvent and melting induced microspheres sintering techniques:a comparative study of morphology and mechanical properties[J]. J Mater Sci Mater Med,2011,22(9):2019-2028.
[9]安森博,汪龙,胡懿郃.聚乳酸-羟基乙酸共聚物载药微球性质及缓释行为的影响因素[J].中国医院药学杂志,2016,36(13):1140-1144.
[10]杜超,王阳,杨彬,等.六种释放曲线相似性评价方法在非洛地平缓释片中的应用比较[J].中国药剂学杂志(网络版),2013,11(4):78-83.
[11]卢文彪,曾元儿,钟镜金,等.丹参制剂中丹参酮ⅡA的稳定性影响因素考察[J].时珍国医国药,2002,13(1):7-9.
[12] Wang H,Zhang G X,Sui H,et al. Comparative studies on the properties of glycyrrhetinic acid-loaded PLGA microparticles prepared by emulsion and template methods[J]. Int J Pharm,2015,496(2):723-731.
[13] Asad Ullah,刘国权,王浩,等.应用Image J程序包进行材料显微组织图像处理、分析和可视化的一种框架(英文)[J].中国体视学与图像分析, 2012,17(4):301-312.
[14] Aragón D M,Rosas J E,Martínez F. Relationship between the solution thermodynamic properties of naproxen in organic solvents and its release profiles from PLGA microspheres[J]. J Microencapsul,2013,30(3):218-224.
[15]王恺源,高永良.影响PLGA微球突释的因素以及控制技术[J].中国新药杂志,2011,20(6):557-562.
[16]韩蕾,潘峰,陈庆华.有机溶剂移除工艺对微球性质及药物释放的影响[J].中国医药工业杂志,2010,41(9):692-697.
[17]王虹,张广兴,刘艳华,等.溶剂体系对甘草次酸微球性能的影响研究[J].中国医院药学杂志,2016,36(22):1947-1950.
[18] Mao S R,Shi Y,Li L,et al. Effects of process and formulation parameters on characteristics and internal morphology of poly(D,L-lactide-co-glycolide)microspheres formed by the solvent evaporation method[J]. Eur J Pharm Biopharm,2008,68(2):214-223.
[19]周雪.基于乳化溶剂挥发法的缓释微球制备及性能研究[D].贵阳:贵阳医学院,2015.
[20] Grizic'D, Lamprecht A. Microparticle preparation by a propylene carbonate emulsification-extraction method[J]. Int J Pharm,2018,544(1):213-221.
[21] Wang S Y,Shi X D,Gan Z H,et al. Preparation of PLGA microspheres with different porous morphologies[J]. Chinese J Polym Sci,2015,33(1):128-136.