Study of critical points of drugs with different solubilities in hydrophilic matrices

Hydrophilic matrices are one of the most popular controlled release systems in the World. It is well known that drug solubility increases the osmotic stress in hydrophilic matrices, resulting in higher swelling through the creation of microcavities and influencing the release rate. Drug solubility also affects the drug release mechanism, favouring the diffusion against the erosion mechanism. Nevertheless it has not been studied whether this can modify the critical points of the hydrophilic matrices. The objective of the present work is to estimate the excipient percolation threshold in HPMC K4M hydrophilic matrices containing acetaminophen, theophiline and ranitidine.HCl, and to study the influence of the drug solubility on the excipient percolation threshold. Dissolution assays were performed using the paddle method. Water uptake was examined using the modified Enslin apparatus. In order to estimate the excipient percolation threshold, the behaviour of the kinetic parameters versus the excipient volume fraction plus initial porosity, was studied. The excipient percolation thresholds were situated between 24.8-25.8, 14.7-18.4 and around 31.2% (v/v) HPMC in theophiline, ranitidine.HCl and acetaminophen matrices, respectively. On the other hand, using these and some previously reported values no relation has been found between drug solubility and excipient percolation threshold in hydrophilic matrices. (C) 2009 Elsevier B.V. All rights reserved.