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Study of the critical points of HPMC hydrophilic matrices for controlled drug delivery

Authors
Journal
International Journal of Pharmaceutics
0378-5173
Publisher
Elsevier
Publication Date
Volume
311
Identifiers
DOI: 10.1016/j.ijpharm.2005.12.012
Keywords
  • Gel Layer
  • Hpmc
  • Swelling
  • Percolation Theory
  • Percolation Threshold
Disciplines
  • Design

Abstract

Abstract The knowledge of the percolation thresholds of a system results in a clear improvement of the design of controlled release dosage forms such as inert matrices. Despite hydrophilic matrices are one of the most used controlled delivery systems in the world, but actuality, the mechanisms of drug release from these systems continue to be a matter of debate nowadays. The objective of the present paper is to apply the percolation theory to study the release and hydration rate of hydrophilic matrices. Matrix tablets have been prepared using KCl as a drug model and HPMC K4M as matrix-forming material, employing five different excipient/drug particle size ratios (ranging from 0.42 to 2.33). The formulations studied containing a drug loading in the range of 20–90% (w/w). Dissolution studies were carried out using the paddle method and the water uptake measurements were performed using a modified Enslin apparatus. 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 percolation theory has been applied for the first time to the study of matrix type controlled delivery systems. The application of this theory allowed to explain changes in the release and hydration kinetics of these matrices. The critical points observed in dissolution and water uptake studies can be attributed to the excipient percolation threshold, being this threshold one of the main factors governing the gel layer formation and consequently, the drug release control from hydrophilic matrices.

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