The influence of crystallization inhibition of HPMC and HPMCAS on model substance dissolution and release in swellable matrix tablets

Journal article, 2011

Poorly soluble compounds are mainly released in particulate form from swellable matrix tablets. If the bioavailability of the drug substance is limited to dissolution, it can be advantageous to formulate the dosage form in a way, which promotes release of molecular form of the drug. In this study, the solid state and dissolution behaviour of amorphous solid dispersions of a model crystalline substance, butylparaben in HPMC and HPMCAS was investigated. In addition, the suitability of HPMCAS both as effective solid solution carrier and as extended release matrix forming polymer was examined. The release from all systems investigated showed extended release capacity with release similar to matrix erosion. However, a detailed study of the factors affecting the release mechanism revealed that upon hydration, the model substance crystallized in the gel layer of the HPMC based formulation, whereas it remained in amorphous form in the HPMCAS tablets. In the case of HPMCAS formulation this effect was attributed to i) the ability of this polymer to keep the model substance in a supersaturated state and ii) the very slow matrix hydration, resulting in a steep concentration gradient of the drug substance and a short diffusion path through the matrix into the dissolution bulk.