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An Atomic Force Microscopy Study of the Effect of Nanoscale Contact Geometry and Surface Chemistry on the Adhesion of Pharmaceutical Particles

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Abstract

Purpose. To understand differences in particle adhesion observed with increasing humidity between samples of salbutamol sulfate prepared by two different methods.

Methods. Atomic force microscopy (AFM) force measurements were performed as a function of humidity (<10% to 65% RH) using two systems. The first system used clean AFM tips against compressed disks of micronized and solution enhanced dispersion by supercritical fluid (SEDS) salbutamol. The second system involved particles of both salbutamol samples mounted onto the apexes of AFM cantilevers, and force measurements being performed against a highly orientated pyrolytic graphite (HOPG) substrate. Following these measurements, the contact asperities of the tips were characterized.

Results. The first system showed a maximum in the observed adhesion at 22% relative humidity (RH) for the SEDS salbutamol compared to 44% RH for the micronized salbutamol. The second system showed a mix of peaks and continual increases in adhesion with humidity. The predicted Johnson-Kendall-Roberts forces were calculated and divided by the actual forces in order to produce a ratio.

Conclusions. By relating the nature of the asperities to the force measurements, we propose a model in which adhesion scenarios range from single asperity nanometer-scale contact in which peaks in the adhesion were observed, to multiasperity contact where a continuous increase in adhesion was seen with humidity.

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Author notes

  1. Jennifer C. Hooton

    Present address: Pharmaceutical Technology Research Group, Department of Pharmacy and Pharmacology, University of Bath, BA2 7AY, U.K.

Authors and Affiliations

  1. Laboratory of Biophysics and Surface Analysis, School of Pharmacy, University of Nottingham, NG7 2RD, U.K.

    Jennifer C. Hooton, Stephanie Allen, Martyn C. Davies, Clive J. Roberts, Saul J. B. Tendler & Philip M. Williams

  2. Nektar, Bradford, BD7 1HR, U.K.

    Caroline S. German

Authors
  1. Jennifer C. Hooton
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  2. Caroline S. German
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  3. Stephanie Allen
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  4. Martyn C. Davies
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  5. Clive J. Roberts
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  6. Saul J. B. Tendler
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  7. Philip M. Williams
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Correspondence to Clive J. Roberts.

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Hooton, J.C., German, C.S., Allen, S. et al. An Atomic Force Microscopy Study of the Effect of Nanoscale Contact Geometry and Surface Chemistry on the Adhesion of Pharmaceutical Particles. Pharm Res 21, 953–961 (2004). https://doi.org/10.1023/B:PHAM.0000029283.47643.9c

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  • DOI: https://doi.org/10.1023/B:PHAM.0000029283.47643.9c

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