Fakhari Amir, Corcoran Marta, Schwarz Alexander
Drug Delivery and Device Development, Medimmune LLC, United States.
Heliyon. 2017 Aug 30;3(8):e00390. doi: 10.1016/j.heliyon.2017.e00390. eCollection 2017 Aug.
Poloxamers are triblock copolymers with a center block of hydrophobic polypropylene oxide (PPO) flanked by two hydrophilic polyethyleneoxide (PEO) blocks. Among this family of copolymers, poloxamer 407 is a non-ionic surfactant with reversible gelation properties above a particular polymer concentration and a particular temperature. Easy preparation of poloxamer 407 based sterile injectable formulations have made this copolymer a good candidate for drug delivery, specifically when controlled release of the drug is required. Previously, the applications of compendial poloxamer 407 preparations were demonstrated; however, low viscosity, poor elasticity, and sol-to-gel transition temperature (T) over a wide temperature range were observed. A purification process was introduced to eliminate impurities and low molecular weight copolymer molecules from the compendial poloxamer 407 resulting in higher viscosity values with T in a narrow temperature range. Here, poloxamer 407 was purified based on the proposed process and the rheological and analytical evaluation of the purified poloxamer 407 was conducted and compared to unpurified, compendial poloxamer 407. Then, the impact of poloxamer 407 concentration on gel formation was evaluated. For drug delivery applications, the effect of relevant buffer salts and the effect of addition of ethanol to the poloxamer 407 solutions were rheologically evaluated.
泊洛沙姆是三嵌段共聚物,其中心嵌段为疏水的聚环氧丙烷(PPO),两侧是两个亲水的聚环氧乙烷(PEO)嵌段。在这一系列共聚物中,泊洛沙姆407是一种非离子表面活性剂,在特定的聚合物浓度和特定温度以上具有可逆凝胶化特性。易于制备基于泊洛沙姆407的无菌注射制剂,使这种共聚物成为药物递送的良好候选者,特别是在需要药物控释的情况下。以前,已证明了药典中泊洛沙姆407制剂的应用;然而,观察到其粘度低、弹性差,并且在很宽的温度范围内溶胶-凝胶转变温度(T)不理想。引入了一种纯化工艺以从药典中的泊洛沙姆407中去除杂质和低分子量共聚物分子,从而在较窄的温度范围内获得更高的粘度值。在此,基于所提出的工艺对泊洛沙姆407进行了纯化,并对纯化后的泊洛沙姆407进行了流变学和分析评估,并与未纯化的药典泊洛沙姆407进行了比较。然后,评估了泊洛沙姆407浓度对凝胶形成的影响。对于药物递送应用,对流变学评估了相关缓冲盐的影响以及向泊洛沙姆407溶液中添加乙醇的影响。