Effect of Polymer Hydration on the Kinetic Release of Drugs: A Study of Ibuprofen and Ketoprofen in HPMC Matrices

Abstract

Samples of drug/hydroxypropylmethylcellulose (HPMC) mixtures and matrices (drug/HPMC mixtures plus excipients) were allowed to equilibrate in closed chambers with defined relative humidities (RHs). Their water uptake and drug release were evaluated by differential scanning calorimetry/thermogravimetric analysis and dissolution studies, respectively. Analysis of the thermal behaviors of the drug/HPMC mixtures and of the polymer alone, as functions of RH, leads to the conclusion that most of the hydration water is retained by the polymer, and points to the occurrence of different types of hydration water, from the strongly polymer-bound water molecules at RH values up to 81%, to the almost “free water” for RH values close to 100%. In addition, application of the Korsmeyer model to the dissolution results leads to the conclusion that the rate determining dissolution processes are predominantly of the fickian type.