Calorimetric investigation on heat release during the disintegration process of pharmaceutical tablets.

ABSTRACT

The compendial USP〈701〉 disintegration test method offers a crucial pass/fail assessment for immediate release tablet disintegration. However, its single end-point approach provides limited insight into underlying mechanisms. This study introduces a novel calorimetric approach, aimed at providing comprehensive process profiles beyond binary outcomes. We developed a novel disintegration reaction calorimeter to monitor the heat release throughout the disintegration process and successfully obtained enthalpy change profiles of placebo tablets with various porosities. The formulation comprised microcrystalline cellulose (MCC), anhydrous lactose, croscarmellose sodium (CCS), and magnesium stearate (MgSt). An abrupt temperature rise was observed after introducing the disintegration medium to tablets, and the relationship between the heat rise time and the tablet's porosity was investigated. The calorimeter's sensitivity was sufficient to discern distinct heat changes among individual tablets, and the analysis revealed a direct correlation between the two. Higher porosity corresponded to shorter heat rise time, indicating faster disintegration rates. Additionally, the analysis identified a concurrent endothermic process alongside the anticipated exothermic phenomenon, potentially associated with the dissolution of anhydrous lactose. Since lactose is the only soluble excipient within the blend composition, the endothermic process can be attributed to the absorption of heat as lactose molecules dissolve in water. The findings from this study underscore the potential of utilising calorimetric methods to quantify the wettability of complex compounds and, ultimately, optimise tablet formulations.