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Pharm Res. 2003 Mar;20(3):508-14.

Characterization of particle-interactions by atomic force microscopy: effect of contact area.

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Laboratory of Biophysics and Surface Analysis, School of Pharmaceutical Sciences, University of Nottingham, NG7 2RD, United Kingdom.



The purpose of this work was to compare adhesion forces, contact area, and work of adhesion of salbutamol sulphate particles produced using micronization and a supercritical fluid technique (solution-enhanced dispersion by supercritical fluids--SEDS) using atomic force microscopy (AFM).


Adhesion forces of individual particles of micronized and SEDS salbutamol against a highly orientated pyrolytic graphite surface were acquired in a liquid environment consistent with that of a pressurized metered dose inhaler. The forces were then related to contact area and work of adhesion.


The raw adhesion force data for the micronized and SEDS material were 14.1 nN (SD 2.5 nN) and 4.2 nN (SD 0.8 nN), respectively. After correction for contact area, the forces per unit area were 13 mN/microm2 (SD 2.3 mN/microm2) and 3 mN/microm2 (SD 0.6 mN/microm2). The average work of adhesion was calculated using the Johnson-Kendall-Roberts theory and was found to be 19 mJm(-2) (SD 3.4 mJm(-2)) for the micronized particle and 4 mJm(-2) (SD 0.8 mJm(-2)) for the SEDS particle.


It is possible to produce a three-dimensional representation of the contact area involved in the interaction and make quantitative comparisons between different particles. There was a lower force per unit area and work of adhesion observed for the SEDS material, possibly because of its lower surface free energy.

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