Flexible modelling of the dissolution performance of directly compressed tablets

In this study, a compartmental disintegration and dissolution model is proposed for the prediction and evaluation of the dissolution performance of directly compressed tablets. This dissolution model uses three compartments (Bound, Disintegrated, and Dissolved) to describe the state of each particle of active pharmaceutical ingredient. The disintegration of the tablet is captured by three fitting parameters. Two disintegration parameters, 𝛽0 and 𝛽𝑡,0, describe the initial disintegration rate and the change in disintegration rate, respectively. A third parameter, 𝛼, describes the effect of the volume of dissolved drug on the disintegration process. As the tablet disintegrates, particles become available for dissolution.

The dissolution rate is determined by the Nernst-Brunner equation, whilst taking into account the hydrodynamic effects within the vessel of a USP II (paddle) apparatus. This model uses the raw material properties of the active pharmaceutical ingredient (solubility, particle size distribution, true density), lending it towards early development activities during which time the amount of drug substance available may be limited. Additionally, the strong correlations between the fitting parameters and the tablet porosity indicate the potential to isolate the manufacturing effects and thus implement the model as part of a real-time release testing strategy for a continuous direct compression line.

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Materials

This study uses data previously published by Bawuah et al. (2021) to demonstrate the application of the dissolution model. Further details of the materials, and the manufacture and characterisation of tablets can be found therein. Two different APIs were investigated: ibuprofen (CAS 15687-27-1, 99.9%) from BLD Pharmatech Ltd (Hong Kong) and indomethacin (CAS 53-86-1, 98.5–100.5%) from Merck (Gillingham, UK). The ibuprofen and indomethacin tablets contained microcrystalline cellulose (MCC, Avicel PH-102®, FMC Europe NV), lactose anhydrous (Supertab® 21AN, DFE Pharma), croscarmellose sodium (CCS, DuPont Nutrition), and magnesium stearate (Fisher Scientific).

Natalie Maclean, John A. Armstrong, Mark A. Carroll, Mohammad Salehian, James Mann, Gavin Reynolds, Blair Johnston, Daniel Markl, Flexible modelling of the dissolution performance of directly compressed tablets, International Journal of Pharmaceutics, Volume 656, 2024, 124084, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.124084.

Read also our introduction article on DC Excipients here: