Effects of HPMC substituent pattern on water up-take, polymer and drug release: An experimental and modelling study
Artikel i vetenskaplig tidskrift, 2017

The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Fick's law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices.

Tablets

MRI

Erosion

Hydrogel-Based Matrices

Dissolution

Diffusion

Drug release

Hydroxypropyl Methylcellulose

Methyl

HPMC

Matrices

NMR microimaging

Texture Analysis

Hydrophilic

Modeling

Cellulose

Hydrogel

Extended release

Författare

D. Caccavo

Universita degli Studi di Salerno

G. Lamberti

Universita degli Studi di Salerno

A. A. Barba

Universita degli Studi di Salerno

Susanna Abrahmsén-Alami

AstraZeneca AB

Anna Viridén

AstraZeneca AB

Anette Larsson

Chalmers, Kemi och kemiteknik, Tillämpad kemi, Farmaceutisk teknologi

International Journal of Pharmaceutics

0378-5173 (ISSN)

Vol. 528 1-2 705-713

Ämneskategorier

Läkemedelskemi

DOI

10.1016/j.ijpharm.2017.06.064