Fundamentals of the powder dissolution temperature of methylcellulose derivatives in aqueous solutions

Powder dissolution temperature (PDT) was recently introduced as a tool with the potential to predict controlled release performance from tablets containing hydroxypropyl methylcellulose (HPMC) 2208. In the current article, the design space was expanded from HPMC 2208 to other HPMC chemistries, as well as to methylcellulose (MC). PDT varied by the cellulose ether chemistry and was determined to be a critical performance attribute for understanding temperature-dependent hydration needs. A critical aspect of the PDT measurement methodology is the use of stirring equipment. Based on a normalization approach, PDT can attain independence from stirring equipment and stirring speed. Furthermore, two competing hypotheses, entropy-controlled and enthalpy-controlled dissolution, are proposed to explain the inverse relationship between temperature and solubility of these macromolecules. The first postulates that dissolution is accompanied by an increase in entropy due to disruption of solid-state structure and the gain in molecular mobility during hydration. In this scenario, the process would be entropically favored (ΔS > 0), and the observed solubility at lower temperatures implies a strongly exothermic enthalpy change (ΔH < 0). The second hypothesis assumes that hydration is associated with formation of ordered supramolecular structures, e.g. micellar structures, which reduce entropy of the system (ΔS < 0).