(T1230-12-80) Calorimetric Investigation on the Disintegration Process of Pharmaceutical Tablets

Purpose: The disintegration process of pharmaceutical solid dosage forms refers to a mechanical break-up of an intact tablet into smaller fragments to enhance the drug substance’s contact with the dissolution medium. This process is particularly critical for immediate-release dosage forms to ensure the end product’s bioavailability and efficacy [1]. Previous studies on this matter have largely focused on the microstructure of the tablets by considering factors such as porosity, pore size distribution, pore connectivity, tortuosity, permeability, hydrophilicity, and so on for different pharmaceutical excipients and manufacturing conditions. These factors have been modelled using capillary force as the driving force and often determined through contact angle measurements. However, limited studies have investigated the temperature rise at the interface between solid and liquid during spontaneous imbibition [2,3]. This is an alternative measurement approach to further characterise disintegration. We hypothesised that the capillary-driven spontaneous imbibition of pharmaceutical tablets could be quantified by measuring the enthalpy change during the disintegration process, and the resulting profiles could be utilised for the analysis of the liquid transport into the tablet matrix.

Methods: To investigate this hypothesis, we developed a novel calorimeter called the ‘disintegration calorimeter.’ Placebo tablets were placed in the test vials, and the system was allowed to reach temperature equilibrium, signifying no noticeable temperature changes. Approximately 1.5 ml of water was then added to the vials, and the temperature changes were monitored for 50 minutes. For the experimental tablets, five batches of complex formulation placebo tablets were produced using HB50 compaction simulator (Huxley Bertram, UK). Each batch was subjected to different target compaction pressures, ranging from 50 MPa to 250 MPa, resulting in five groups with varying porosities ranging from approximately 30% to 10%.

Results: Five distinct temperature change profiles were obtained, each representing a different porosity group. Analysis of the results revealed a strong correlation between the porosity of tablets and the heat release pattern during the disintegration process. The batch with the highest porosity exhibited the most abrupt increase in temperature at the beginning of hydration, followed by a gradual decrease. As the compaction pressure increased, the magnitude of the temperature increase gradually decreased.

Conclusion: In the study, we measured the heat released during the disintegration process using a novel disintegration calorimeter. Although specific thermodynamic contributors were not identified, the observations highlighted a strong correlation between tablet porosity and the enthalpy change during the process. The findings demonstrate the potential of utilising this approach as a novel method for quantifying the hydrophilicity of complex compounds as well as estimating the liquid penetration into the tablet matrix by analysing the correlation between the enthalpy change and the tablet properties.

References: [1] Markl D. and Zeitler J.A. Pharm Res 34. 5 (2017)
[2] Claxton G. J Chromatogr A. 2 (1959)
[3] Aslannejad H et al. Sci Rep-uk 7, 7268 (2017)

Schematic of the experimental setup for calorimetric investigation on the tablet disintegration process

Five enthalpy change profiles were obtained, each representing a different set of porosity of tablets. Analysis of the results revealed a strong correlation between the porosity of the tablet and the heat released during the disintegration process.