The consequence of the chemical composition of HPMC in matrix tablets on the release behaviour of model drug substances having different solubility

This study investigates the effect of the chemical heterogeneity of hydroxypropyl methylcellulose (HPMC) on the release of model drug substances from hydrophilic matrix tablets. The hypothesis was that the release of drug substances could be influenced by possible interactions with HPMC batches having different chemical heterogeneity. The cloud point of the most heterogeneous batch was more affected by the model drug substances, methylparaben and butylparaben, and most by butylparaben with the lowest solubility. The different clouding behaviour was explained by the heterogeneously substituted batches being more associative and the more lipophilic butylparaben being able to interact more efficiently with the hydrophobic HPMC transient crosslinks that formed. Interestingly, tablet compositions of the heterogeneously substituted HPMC batches released the more soluble methylparaben at lower rates than butylparaben. The explanation is that the hydrophobic HPMC interactions with butylparaben made the gel of the tablet less hydrated and more fragile and therefore more affected by erosional stresses. In contrast, drug release from compositions consisting of the more homogeneously substituted batches was affected to a minor extent by the drugs and was very robust within the experimental variations. The present study thus reveals that there can be variability in drug release depending on the lipophilicity of the drug and the substituent heterogeneity of the HPMC used.

Drug release from hydrophilic matrices composed of HPMC with different substituent heterogeneity. The more heterogeneously substituted batches interacted with the poorly soluble drug to greater extent, which significantly increased the polymer erosion from the matrix. The increased erosion contributed to that the poorly soluble drug was released with a faster rate than the more soluble model drug. In contrast, the drug release from matrixes composed of more homogeneously substituted HPMC batches followed the expected drug release behaviour, where the poorly soluble drug was released with lower rates and with a greater erosional contribution to the release mechanism. Consequently, both the substituent heterogeneity of HPMC as well as the polymer-drug interactions highly influences the drug release from matrix tablets.Figure optionsDownload as PowerPoint slide