Release of theophylline and carbamazepine from matrix tablets – Consequences of HPMC chemical heterogeneity

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.

Graphical abstractDrug release from hydrophilic matrices composed of two HPMC batches of the same substituent and viscosity grade but with different substituent heterogeneity. The release of the poorly soluble carbamazepine was considerably slower from matrices composed of the HPMC with heterogeneous substituent pattern. This was explained by slower polymer erosion of the heterogeneous HPMC and the fact that carbamazepine was mainly released by erosion. The release of the sparingly soluble theophylline was more comparable from the two formulations, which was explained by the similar water transports into the tablets and the similar diffusion paths of theophylline..Figure optionsDownload full-size imageDownload as PowerPoint slide