Deeper insight into the drug release mechanisms in Eudragit RL-based delivery systems.

Tartaric acid, metoprolol free base and metoprolol tartrate act as plasticisers for Eudragit RL, in the dry but also in the wet state. Fitting analytical solutions of Fick's second law of diffusion allowed for the determination of the apparent diffusivities of water and of tartaric acid, metoprolol free base and metoprolol tartrate upon exposure of thin films to 0.1M HCl, phosphate buffer pH 7.4 and distilled water. Based on these calculations, it could be shown that water penetration into the systems is predominantly controlled by pure diffusion, irrespective of the type of bulk fluid. Interestingly, the plasticising effect of metoprolol tartrate was much more pronounced than that of tartaric acid, resulting in monotonically increasing diffusion coefficients with increasing initial drug content. In contrast, the plasticising activity of metoprolol free base was very limited in the wet state, due to drug precipitation in aqueous environments. Partially observed film shrinking (after an initial system swelling) could be attributed to the leaching of the plasticising compound into the release medium, resulting in less flexible polymeric networks and squeezing out of water. Also the release of tartaric acid, metoprolol free base and metoprolol tartrate into the investigated bulk fluids was predominantly diffusion controlled. However, the precipitation of the free base in wet films rendered the mass transport mechanisms more complex, at moderate and high initial drug loadings. The obtained new insight into the underlying drug release mechanisms in Eudragit RL networks can help to facilitate the optimisation of this type of dosage forms.

Characterisation of quaternary polymethacrylate films containing tartaric acid, metoprolol free base or metoprolol tartrate.

The aim of this study was to better understand the interactions between metoprolol tartrate and quaternary polymethacrylate (Eudragit RL and Eudragit RS) films. For reasons of comparison, polymeric films containing the free base metoprolol or free tartaric acid were also prepared. Systems containing various amounts of the free base, free acid and the salt were characterised using polarising light microscopy, X-ray powder diffraction, differential scanning calorimetry and mechanical analysis (puncture test). The free base is the most efficient plasticiser of the three species for Eudragit RL and Eudragit RS, but with limited solubility in the polymers. Due to its hydrophobicity, it can interact with the hydrophobic polymer backbones. In contrast, in salt containing films, ionic interactions between the positively charged quaternary ammonium groups and the negatively charged tartrate anions apparently occur, this being suggested by the different effects on Eudragit RL versus RS, which have different contents of quaternary ammonium groups. Importantly, the combination of acid and base as a salt avoids drug precipitation at higher metoprolol contents. The obtained new insight into the occurring drug-polymer interactions can help to facilitate the development/optimisation of this type of dosage forms.