Investigation into the Effect of Humidity on Drug–Drug Interactions Using the Atomic Force Microscope

• Published in: Journal of pharmaceutical sciences Vol. 92; no. 4; pp. 815 - 822
• Main Authors: Young, Paul M., Price, Robert, Tobyn, Michael J., Buttrum, Mark, Dey, Fiona
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.04.2003; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: Albuterol - chemistry; atomic force microscope; Biological and medical sciences; Chemical Phenomena; Chemistry, Pharmaceutical; Chemistry, Physical; Colloids; Drug Compounding; Drug Interactions; dry powder aerosolization; force volume; General pharmacology; Humidity; Medical sciences; Microscopy, Atomic Force - methods; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Powders - chemistry; atomic force microscope; humidity; force volume; dry powder aerosolization; Atomic force microscopy; Humidity; Inhaler; Micronization; Drug interaction; Salbutamol; Powder
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.10250

The atomic force microscope (AFM) has been used to characterize the cohesive nature of a micronized pharmaceutical powder used for inhalation therapy. Salbutamol sulfate (also referred to as albuterol sulfate), a therapeutic drug commonly delivered from dry powder inhalers (DPI), was chosen as a model system because the cohesion and subsequent de‐agglomeration during inhalation are critical aspects to the efficacy of such a delivery system. Salbutamol sulfate drug particulates were mounted on V‐shaped AFM cantilevers using a novel micromanipulation technique. Force–distance curves obtained from the measurements between cantilever drug probes and model compacts of salbutamol sulfate were integrated to determine separation energies. The effect of humidity (15–75% RH) on the energy required to separate a drug particle from model drug surface was determined using a custom‐built perfusion apparatus attached to the AFM. Separation energy measurements over 10 × 10‐μm areas of the compact surface (n = 4096) exhibited log normal distributions (apparent linear regression, R2 ≥ 0.97). Significant increases in the median separation energies (p < 0.05) between the salbutamol sulfate drug probes and salbutamol sulfate model surfaces were observed as humidity was increased. This result is most likely attributed to capillary interactions becoming more dominant at higher humidities. This investigation has shown the AFM to be a powerful technique for quantification of the separation energies between micronized drug particulates, highlighting the potential of the AFM as a rapid preformulation tool. © 2003 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:815–822, 2003