Young Paul M, Price Robert, Tobyn Michael J, Buttrum Mark, Dey Fiona
Pharmaceutical Technology Research Group, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK.
J Pharm Sci. 2004 Mar;93(3):753-61. doi: 10.1002/jps.10549.
The influence of relative humidity (RH) on the cohesion properties of three drugs: salbutamol sulphate (SS), triamcinolone acetonide (TAA), and disodium cromoglycate (DSCG) was investigated using the atomic force microscope (AFM) colloidal probe technique. Micronized drug particles were mounted in heat-sensitive epoxy resin for immobilization. Multiple AFM force-distance curves were conducted between each drug probe and the immobilized drug particulates at 15, 45, and 75% RH using Force-Volume imaging. Clear variations in the cohesion profile with respect to RH were observed for all three micronized drugs. The calculated force and energy of cohesion to separate either micronized SS or DSCG increased as humidity was raised from 15 to 75% RH, suggesting capillary forces become a dominating factor at elevated RH. In comparison, the separation force and energy for micronized TAA particles decreased with increased RH. This behavior may be attributed to long-range attractive electrostatic interactions, which were observed in the approach cycle of the AFM force-distance curves. These observations correlated well with previous aerosolization studies of the three micronized drugs.
使用原子力显微镜（AFM）胶体探针技术研究了相对湿度（RH）对三种药物：硫酸沙丁胺醇（SS）、曲安奈德（TAA）和色甘酸钠（DSCG）内聚特性的影响。将微粉化药物颗粒固定在热敏环氧树脂中。使用力-体积成像在15%、45%和75%相对湿度下，在每个药物探针与固定的药物颗粒之间进行多条AFM力-距离曲线测量。观察到所有三种微粉化药物的内聚特性随相对湿度有明显变化。随着湿度从15%提高到75%，分离微粉化SS或DSCG所需的计算力和内聚能增加，这表明在较高相对湿度下毛细作用力成为主导因素。相比之下，微粉化TAA颗粒的分离力和能量随相对湿度增加而降低。这种行为可能归因于在AFM力-距离曲线的接近过程中观察到的长程吸引静电相互作用。这些观察结果与之前对这三种微粉化药物的雾化研究结果高度相关。
