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The Effects of Milling on the Surface Properties of Form I Paracetamol Crystals

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Abstract

Purpose

The effects of milling and particle size on surface energies of form I paracetamol crystals are reported.

Methods

Paracetamol crystals (75–850 μm) were obtained by cooling methanol and acetone saturated solutions. Additionally, macroscopic (>2 cm) single crystals were grown by slow solvent evaporation from saturated solutions, ball milled and sieved into different particle size fractions. Surface properties were characterised using Inverse Gas Chromatography and compared with those calculated from sessile drop contact angle measurements on macroscopic single crystals.

Results

Dispersive surface energies, \( \gamma ^{d}_{{{\text{SV}}}} \) for milled samples increased by 20% with decreasing particle size. With decreasing particle size acceptor numbers, K A values were constant but donor numbers, K B decreased. For unmilled materials K B was comparable to K A but with a significantly lower \( \gamma ^{d}_{{{\text{SV}}}} \)of only 33 mJ/m2. Milling resulted in fracture along the crystal's lowest attachment energy plane (010), exposing facets of different surface chemistry to that of the native external facets. θ for the (010) fracture plane confirmed a higher \( \gamma ^{d}_{{{\text{SV}}}} \) compared to external facets such as (011) of single crystals.

Conclusions

Milling exposes a hydrophobic surface for paracetamol form I crystals which becomes increasingly more dominant with decreasing particle size.

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Authors and Affiliations

  1. Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK

    Jerry Y. Y. Heng & Daryl R. Williams

  2. Surface Measurement Systems Ltd., 5 Wharfside, Rosemount Road, London, HA0 4PE, UK

    Frank Thielmann & Daryl R. Williams

Authors
  1. Jerry Y. Y. Heng
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  2. Frank Thielmann
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  3. Daryl R. Williams
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Correspondence to Daryl R. Williams.

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Heng, J.Y.Y., Thielmann, F. & Williams, D.R. The Effects of Milling on the Surface Properties of Form I Paracetamol Crystals. Pharm Res 23, 1918–1927 (2006). https://doi.org/10.1007/s11095-006-9042-1

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  • DOI: https://doi.org/10.1007/s11095-006-9042-1

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