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Understanding improved dissolution of indomethacin through the use of cohesive poorly water-soluble aluminium hydroxide: Effects of concentration and particle size distribution

Version 2 2024-06-04, 15:49
Version 1 2020-02-04, 15:54
journal contribution
posted on 2024-06-04, 15:49 authored by T Tay, A Allahham, David Morton, PJ Stewart
The objective of this study was to explore the effects of concentration and particle size distribution of an added poorly water‐soluble inorganic salt, aluminium hydroxide, on the dissolution of a poorly water‐soluble drug, indomethacin (IMC), from lactose interactive mixtures. Dissolution was studied using the United States Pharmacopeia paddle method in buffer pH 5.0 and the data most aptly fitted a bi‐exponential dissolution model which represented dissolution occurring from dispersed and agglomerated particles. The dispersion of IMC mixtures was measured in dissolution media under non‐sink conditions by laser diffraction. The dissolution of IMC increased as a function of the concentration of aluminium hydroxide (5–20%) added to the mixtures. Increasing the proportion of larger particles of the cohesive aluminium hydroxide increased the dissolution rate of IMC. The enhanced dissolution was attributed to increases in both the dissolution rate constant and initial concentration of dispersed particles. Mechanistically, the aluminium hydroxide was found to facilitate the detachment of IMC particles from the carrier surface, forming a complex interactive mixture that more readily deagglomerated than the cohesive drug agglomerates. The outcomes of this work would therefore allow more careful control and selection of the excipient specifications in producing solid dosage formulations with improved dissolution of poorly water‐soluble drugs.

History

Journal

Journal of Pharmaceutical Sciences

Volume

100

Pagination

4269-4280

Location

New York, N.Y.

ISSN

0022-3549

eISSN

1520-6017

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2011, Wiley-Liss and American Pharmacists Association

Issue

10

Publisher

Elsevier