Release of theophylline and carbamazepine from matrix tablets - Consequences of HPMC chemical heterogeneity
Journal article, 2011
The release of theophylline and carbamazepine from matrix tablets composed of microcrystalline cellulose, lactose and hydroxypropyl methylcellulose (HPMC) was studied. The aim was to investigate the effect of different substituent heterogeneities of HPMC on the drug release from matrix tablets composed of either 35% or 45% HPMC. The release of the poorly soluble carbamazepine was considerably affected by the HPMC heterogeneity, and the time difference at 80% drug release was more than 12 h between the formulations of different HPMC batches. This was explained by slower polymer erosion of the heterogeneous HPMC and the fact that carbamazepine was mainly released by erosion. In addition, results from magnetic resonance imaging showed that the rate of water transport into the tablets was similar. This explained the comparable results of the release of the sparingly soluble theophylline from the two formulations even though the polymer erosion and the swelling of the tablets were considerably different. Thus, it can be concluded that the drug release was highly affected by the substituent heterogeneity, especially in the case of carbamazepine, which was released mainly by erosion. (C) 2011 Elsevier B.V. All rights reserved.
HPMC chemical heterogeneity
Drug solubility
hydroxypropylmethylcellulose
physicochemical properties
matrices
kinetics
hydrophilic
dissolution
polymer particle-size
hydroxypropyl methylcellulose matrices
Batch-to-batch variability
Hydrophilic matrix tablets
diffusion
Drug release
delivery-systems
drug-release
MRI
Author
Anna Viridén
Chalmers, Chemical and Biological Engineering, Pharmaceutical Technology
SuMo Biomaterials
Susanna Abrahmsén-Alami
AstraZeneca Sweden
Bengt Wittgren
AstraZeneca Sweden
Anette Larsson
Chalmers, Chemical and Biological Engineering, Pharmaceutical Technology
SuMo Biomaterials
European Journal of Mineralogy
0935-1221 (ISSN)
Vol. 78 3 470-479Subject Categories (SSIF 2011)
Chemical Sciences
DOI
10.1016/j.ejpb.2011.02.003