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首页> 外文期刊>Journal of Applied Polymer Science >Solute and solvent effects on the thermorheological properties of poly(oxyethylene)-poly(oxypropylene) block copolymers: Implications for pharmaceutical dosage form design
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Solute and solvent effects on the thermorheological properties of poly(oxyethylene)-poly(oxypropylene) block copolymers: Implications for pharmaceutical dosage form design

机译：溶质和溶剂对聚（氧乙烯）-聚（氧丙烯）嵌段共聚物的热流变性能的影响：对药物剂型设计的启示

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Despite their widespread use as platforms for topical drug delivery systems, there is a relative lack of information concerning the thermorheological and viscoelastic properties of poloxamer systems and the effects of formulation components on these properties. To address this deficit, we examined the effects of the poloxamer concentration (25 and 35% w/w), molecular weight blend (poloxamer 407 and poloxamer 188), cosolvents (ethanol, propylene glycol, and glycerol), and presence of inorganic and organic electrolytes (sodium chloride and tetracaine hydrochloride, respectively) on these properties. The rheological properties were examined with a rheometer (4-cm-diameter, stainless steel, parallel-plate geometry) in either thermal sweep (0.5 Hz) or frequency sweep (0.01-1.0 Hz and 37degreesC) modes. Increasing the poloxamer concentration increased the elasticity [i.e., increased the storage modulus (G') and reduced the loss tangent (tan 5)] and reduced the sol-gel transition temperature (T,,) of all the formulations. Decreasing the ratio (407:188) increased T-m and reduced the elasticity of all the formulations. Increasing the concentration of ethanol, propylene glycol, or glycerol in the solvent reduced T-m. The presence of ethanol reduced G' and increased tan 8 in a concentration-dependent fashion, whereas the viscoelastic properties of the poloxamers were more tolerant of glycerol (in particular) and propylene glycol. The elasticity of the formulations containing up to 10% glycerol and 5% propylene glycol was increased with respect to their aqueous counterparts. The presence of sodium chloride reduced T-m and, at lower concentrations (1 and 3%), increased G' and reduced tan 5 for aqueous poloxamer systems. Conversely, the addition of a model therapeutic agent, tetracaine hydrochloride (5 and 7% w/w), significantly increased T. and altered the viscoelastic character of the poloxamer system, notably reducing G' and increasing the loss modulus and tan 8. Alterations in the viscoelastic and thermorheological properties of aqueous poloxamer systems will have implications for their clinical performance. This study, therefore, has highlighted the need for the rational selection of components in the formulation of poloxamer systems as platforms for topical drug delivery. (C) 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1016 -1026, 2003. [References: 32]
机译：尽管它们广泛用作局部药物递送系统的平台，但是相对缺乏关于泊洛沙姆系统的热流变和粘弹性性质以及制剂组分对这些性质的影响的信息。为了解决这一不足，我们研究了泊洛沙姆浓度（25和35％w / w），分子量共混物（泊洛沙姆407和泊洛沙姆188），助溶剂（乙醇，丙二醇和甘油）以及存在无机盐和水的影响。有机电解质（分别为氯化钠和盐酸丁卡因）的这些特性。用流变仪（直径4厘米，不锈钢，平行板几何形状）以热扫描（0.5 Hz）或频率扫描（0.01-1.0 Hz和37℃）模式检查流变性能。泊洛沙姆浓度的增加增加了所有制剂的弹性[即，增加了储能模量（G'）并降低了损耗角正切值（tan 5）]，并降低了所有制剂的溶胶-凝胶转变温度（T ，，）。降低比例（407：188）会增加T-m并降低所有配方的弹性。增加溶剂中乙醇，丙二醇或甘油的浓度会降低T-m。乙醇的存在以浓度依赖的方式降低了G'并增加了tan 8，而泊洛沙姆的粘弹性能更耐受甘油（尤其是丙二醇）和丙二醇。相对于其水性对应物，包含至多10％的甘油和5％的丙二醇的制剂的弹性增加。氯化钠的存在降低了T-m，而在较低浓度（1％和3％）下，泊洛沙姆水溶液体系的G'增加且tan 5降低。相反，添加模型治疗剂盐酸丁卡因（5％和7％w / w）会显着增加T.并改变泊洛沙姆系统的粘弹性，特别是降低G'并增加损耗模量和tan 8。泊洛沙姆水溶液体系的粘弹性和热流变特性对其临床性能将产生影响。因此，这项研究强调了在泊洛沙姆系统的配方中应合理选择成分，以作为局部给药的平台。 （C）2002 Wiley Periodicals，Inc. J Appl Polym Sci 87：1016 -1026，2003。[参考：32]

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