Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485284 | Journal of Pharmaceutical Sciences | 2011 | 12 Pages |
Abstract
The objective of this study was to explore the effects of concentration and particle size distribution of an added poorly waterâsoluble inorganic salt, aluminium hydroxide, on the dissolution of a poorly waterâsoluble 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 biâexponential dissolution model which represented dissolution occurring from dispersed and agglomerated particles. The dispersion of IMC mixtures was measured in dissolution media under nonâsink 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 waterâsoluble drugs. © 2011 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 100:4269-4280, 2011
Keywords
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Tracy Tay, Ayman Allahham, David A.V. Morton, Peter J. Stewart,