Ooi Jesslynn, Gaisford Simon, Boyd Ben J, Young Paul M, Traini Daniela
Respiratory Technology, Woolcock Institute of Medical Research, 431 Glebe Point Road, Glebe, NSW 2037, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
Int J Pharm. 2014 Jan 30;461(1-2):301-9. doi: 10.1016/j.ijpharm.2013.11.055. Epub 2013 Dec 8.
The purpose of this work was to evaluate gas perfusion isothermal calorimetry (ITC) as a method to characterize the physicochemical changes of active pharmaceutical ingredients (APIs) intended to be formulated in pressurized metered dose inhalers (pMDIs) after exposure to a model propellant. Spray dried samples of beclomethasone dipropionate (BDP) and salbutamol sulphate (SS) were exposed to controlled quantities of 2H,3H-decafluoropentane (HPFP) to determine whether ITC could be used as a suitable analytical method for gathering data on the behavioural properties of the powders in real time. The crystallization kinetics of BDP and the physiochemical properties of SS were successfully characterized using ITC and supported by a variety of other analytical techniques. Correlations between real and model propellant systems were also established using hydrofluoroalkane (HFA-227) propellant. In summary, ITC was found to be suitable for gathering data on the crystallization kinetics of BDP and SS. In a wider context, this work will have implications on the use of ITC for stability testing of APIs in HFA-based pMDIs.
本研究旨在评估气体灌注等温滴定量热法（ITC），作为一种表征活性药物成分（API）物理化学变化的方法。这些活性药物成分拟用于加压定量吸入器（pMDI）中，在接触模型推进剂后进行分析。将倍氯米松二丙酸酯（BDP）和硫酸沙丁胺醇（SS）的喷雾干燥样品暴露于定量的2H,3H-十氟戊烷（HPFP）中，以确定ITC是否可作为一种合适的分析方法，用于实时收集有关粉末行为特性的数据。使用ITC成功地表征了BDP的结晶动力学和SS的物理化学性质，并得到了多种其他分析技术的支持。还使用氢氟烷烃（HFA-227）推进剂建立了实际推进剂系统与模型推进剂系统之间的相关性。总之，发现ITC适用于收集有关BDP和SS结晶动力学的数据。从更广泛的角度来看，这项工作将对ITC用于基于HFA的pMDI中API的稳定性测试产生影响。
