Etherson Kelly, Halbert Gavin, Elliott Moira
Cancer Research UK Formulation Unit, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
J Pharm Pharmacol. 2016 Sep;68(9):1131-42. doi: 10.1111/jphp.12602. Epub 2016 Jul 1.
The aim of this study was to determine the influence of non-ionisable excipients hydroxypropyl-β-cyclodextrin (HPβCD) and poloxamers 407 and 188 on the supersaturation and precipitation kinetics of ibuprofen, gliclazide, propranolol and atenolol induced through solution pH shifts using the CheqSol method.
The drug's kinetic and intrinsic aqueous solubilities were measured in the presence of increasing excipient concentrations using the CheqSol method. Experimental data rate of change of pH with time was also examined to determine excipient-induced parachute effects and influence on precipitation rates.
The measured kinetic and intrinsic solubilities provide a determination of the influence of each excipient on supersaturation index, and the area under the CheqSol curve can measure the parachute capability of excipients. The excipients influence on precipitation kinetics can be measured with novel parameters; for example, the precipitation pH or percentage ionised drug at the precipitation point, which provide further information on the excipient-induced changes in precipitation performance.
This method can therefore be employed to measure the influence of non-ionisable excipients on the kinetic solubility behaviour of supersaturated solutions of ionisable drugs and to provide data, which discriminates between excipient systems during precipitation.
本研究旨在通过CheqSol方法，确定非离子型辅料羟丙基-β-环糊精（HPβCD）以及泊洛沙姆407和188对因溶液pH值变化诱导的布洛芬、格列齐特、普萘洛尔和阿替洛尔的过饱和及沉淀动力学的影响。
使用CheqSol方法，在辅料浓度不断增加的情况下，测量药物的动力学和固有水溶解度。还研究了pH值随时间变化的实验数据速率，以确定辅料诱导的降落伞效应以及对沉淀速率的影响。
所测得的动力学和固有溶解度可确定每种辅料对过饱和指数的影响，并且CheqSol曲线下的面积能够衡量辅料的降落伞能力。辅料对沉淀动力学的影响可用新参数来衡量；例如，沉淀pH值或沉淀点处的离子化药物百分比，这些参数能提供有关辅料诱导的沉淀性能变化的更多信息。
因此，该方法可用于测量非离子型辅料对可离子化药物过饱和溶液动力学溶解行为的影响，并提供在沉淀过程中区分辅料体系的数据。
