Evaluating hemicellulose-API miscibility using melting point depression

To improve the solubility of poorly soluble APIs, amorphous solid dispersions (ASDs) are commonly employed. For an ASD to remain stable and effective, sufficient miscibility between the API and the polymeric carrier is essential. Although hemicelluloses possess several favourable attributes compared with commonly used synthetic polymers, they are not yet widely applied in pharmaceutical formulation research due to limited understanding of their behavior in pharmaceutical mixtures. In this study, we demonstrate that Flory-Huggins theory combined with melting point depression measurements can be used to estimate the miscibility between hemicelluloses and APIs. Based on these analyses, all three model APIs were found to be immiscible with both hemicelluloses. The resulting phase diagrams indicate that, at room temperature, only ASDs containing minimal API fractions would remain stable. This suggests that hemicelluloses may have a limited ability to form thermodynamically stable mixtures with lipophilic drugs. However, they may still be able to stabilize APIs in amorphous form and enhance dissolution properties through other mechanisms.