Counter-intuitive enhancement in the dissolution of indomethacin with the incorporation of cohesive poorly water-soluble inorganic salt additives

Tay, T, Allahham, A, Morton, D and Stewart, P 2011, 'Counter-intuitive enhancement in the dissolution of indomethacin with the incorporation of cohesive poorly water-soluble inorganic salt additives', European Journal of Pharmaceutics and Biopharmaceutics, vol. 79, no. 3, pp. 674-682.


Document type: Journal Article
Collection: Journal Articles

Title Counter-intuitive enhancement in the dissolution of indomethacin with the incorporation of cohesive poorly water-soluble inorganic salt additives
Author(s) Tay, T
Allahham, A
Morton, D
Stewart, P
Year 2011
Journal name European Journal of Pharmaceutics and Biopharmaceutics
Volume number 79
Issue number 3
Start page 674
End page 682
Total pages 9
Publisher Elsevier
Abstract The objective of this work was to investigate the influence of various micronized poorly water-soluble inorganic materials on the dissolution and de-agglomeration behaviour of a micronized, poorly water-soluble model drug, indomethacin, from lactose interactive mixtures. Dissolution of indomethacin was studied using the USP paddle method and the data were modelled with multi-exponential equations using a nonlinear least squares algorithm in order to obtain key parameter estimates. The dispersion of indomethacin mixtures was measured by laser diffraction. The addition of aluminium hydroxide and calcium phosphate to binary mixtures of indomethacin counter-intuitively improved the dissolution rate of indomethacin due to significant increases in both the estimated initial concentration and dissolution rate constant of dispersed particles of indomethacin. While some enhancement was due to pH changes in the dissolution medium, the presence of these poorly water-soluble inorganic salts caused de-agglomeration. Average particle size distributions indicated that the presence of aluminium hydroxide within the matrix of indomethacin had reduced the agglomerate concentration whilst increasing the dispersed particle concentration. These findings provide the first evidence of the ability of poorly water-soluble inorganic salts to enhance the de-agglomeration and dissolution of micronized powders, potentially translating to improved bioavailability of poorly water-soluble drugs.
Subject Pharmaceutical Sciences
Keyword(s) De-agglomeration
Dissolution
Dissolution modelling
Indomethacin interactive mixtures
Poorly water-soluble drugs
Poorly water-soluble inorganic salts
DOI - identifier 10.1016/j.ejpb.2011.06.002
Copyright notice © 2011 Elsevier
ISSN 0939-6411
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