Jones Stuart A, Reid Monica L, Brown Marc B
Pharmaceutical Science Research Division, King's College, London, London, UK.
J Pharm Sci. 2009 Feb;98(2):543-54. doi: 10.1002/jps.21448.
A transiently supersaturated drug delivery system has the potential to enhance topical drug delivery via heightened thermodynamic activity. The aim of this work was to quantify the degree of saturation (DS) for transiently supersaturated formulations using three traditional and one novel in vitro assessment methods. Metered dose aerosols (MDA) were formulated containing saturated levels of beclomethasone dipropionate monohydrate (BDP) or betamethasone 17-valerate (BMV) within a pressurised canister, and included ethanol (EtOH), hydrofluoroalkane 134a propellant and poly(vinyl pyrrolidone). Attempts to determine the DS via the measurement of drug flux through synthetic membranes did not correlate and was shown to be dependent on the EtOH concentration. The inability of these methods to accurately assess the drug DS may be due to the transient nature of the formulation and the volatile solvents dehydrating the membrane. A mathematical equation that used the evaporation rate of the formulation was derived to determine the theoretical DS at various time points after MDA actuation. It was shown that the MDAs became supersaturated with a high DS, this enhanced drug release from the formulation and therefore these preparations have the potential to increase the amount of drug delivered into the skin.
瞬态过饱和药物递送系统有可能通过提高热力学活性来增强局部药物递送。本研究的目的是使用三种传统的和一种新型的体外评估方法来量化瞬态过饱和制剂的饱和度（DS）。在加压罐中配制含有饱和水平的倍氯米松二丙酸酯一水合物（BDP）或倍他米松17-戊酸酯（BMV）的定量气雾剂（MDA），并包含乙醇（EtOH）、氢氟烷烃134a推进剂和聚（乙烯基吡咯烷酮）。通过测量药物透过合成膜的通量来确定DS的尝试没有相关性，并且显示出取决于EtOH浓度。这些方法无法准确评估药物DS可能是由于制剂的瞬态性质以及挥发性溶剂使膜脱水。推导了一个使用制剂蒸发速率的数学方程，以确定MDA启动后不同时间点的理论DS。结果表明，MDA以高DS达到过饱和，这增强了药物从制剂中的释放，因此这些制剂有潜力增加递送至皮肤的药物量。
