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J Pharm Sci. 2007 Oct;96(10):2746-56.

Investigation of the influence of particle size on the excipient percolation thresholds of HPMC hydrophilic matrix tablets.

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Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain.


In previous papers of our research group, a linear relationship between the drug percolation threshold and the relative drug particle size (drug/excipient) has been found, in the case of the inert matrices. The objective of the present paper is to investigate the influence of the particle size on the excipient percolation threshold in the case of hydrophilic matrices. This influence can have important consequences on the release behaviour of these controlled release devices. Matrix tablets have been prepared using KCl/Lobenzarit Disodium as drugs and HPMC K4M as matrix forming material, employing six different excipient/drug particle size ratios (ranging from 0.42 to 4.16). The formulations studied contain a drug loading in the range of 20-90% (w/w). In order to estimate the percolation threshold, the behaviour of the kinetic parameters with respect to the volumetric fraction of each component at time zero, was studied. The obtained results support the existence of a linear relationship between a component percolation threshold (drug or excipient) and its relative particle size (drug/excipient in the case of the drug percolation threshold or excipient/drug in the case of the excipient percolation threshold). This relationship is valid for different drugs, excipients and systems (inert or hydrophilic matrix tablets).

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