Study of morphine hydrochloride percolation threshold in Eudragit® RS–PM matrices

Abstract

Percolation theory has been applied in the pharmaceutical field since 1987. 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. In the present paper, the percolation thresholds of morphine hydrochloride inert matrices have been estimated and the obtained results have been applied to the design of controlled release inert matrices of this drug. The tablets were prepared by compression of binary mixtures of morphine hydrochloride, as a drug of clinical interest to cancer patients, and Eudragit® RS–PM, a hydrophobic acrylic polymer as matrix forming material. Drug loadings between 10% and 90% (w/w) were prepared, keeping constant the drug and excipient particle sizes. The dissolution assay was carried out exposing only one side of the tablets to the dissolution medium. The drug percolation threshold was estimated following the method of Leuenberger and Bonny as 0.506±0.014 of total porosity, corresponding to ca. 40% (w/w) drug content. The scanning electron microscopy (SEM) micrographs corresponding to the tablet side facing the lower punch and to the cross-section of these matrices are in agreement with the estimated percolation range.On the other hand, according to the SEM study and to the tablet integrity after the release assays, the excipient percolation threshold is expected to range from 65 to 80% (w/w) of drug, i.e. from 29.5 to 17% (v/v) of excipient. The release profiles of the matrices situated above the percolation threshold of the swelling substances (more than 41% v/v of excipient) have shown practically linear release profiles, which appear to not be sensitive to the drug load.