Graham P D, Brodbeck K J, McHugh A J
Department of Chemical Engineering, University of Illinois, 600 S. Mathews, Urbana, IL 61801, USA.
J Control Release. 1999 Mar 29;58(2):233-45. doi: 10.1016/s0168-3659(98)00158-8.
Dark ground optical microscopy, electron microscopy, and high performance liquid chromatography (HPLC) have been used to quantify the effects of formulation changes on the phase inversion dynamics and in vitro drug release properties of a PLGA-based drug delivery system. Gel growth rates and water influx rates are determined from plots of the square of the respective front motion with time. Results show that additives that accelerate the solution gelation rate at constant morphology result in high initial release rates. Conversely, additives that slow the rate of gelation dramatically reduce the initial drug release rate and lead to a more dense sponge-like morphology. Moreover, the phase inversion dynamics and morphology are the same regardless of whether the solutions are quenched with water, a PBS buffer solution or horse serum.
暗视野光学显微镜、电子显微镜和高效液相色谱法(HPLC)已被用于量化制剂变化对基于聚乳酸-羟基乙酸共聚物(PLGA)的药物递送系统的相转变动力学和体外药物释放特性的影响。凝胶生长速率和水流入速率由各自前沿运动的平方随时间的曲线确定。结果表明,在形态保持恒定的情况下,加速溶液凝胶化速率的添加剂会导致较高的初始释放速率。相反,减缓凝胶化速率的添加剂会显著降低药物的初始释放速率,并导致形成更致密的海绵状形态。此外,无论溶液是用水、磷酸盐缓冲盐水(PBS)溶液还是马血清淬灭,相转变动力学和形态都是相同的。