Disintegration and dissolution are among the most observed phenomena in granular products. However, in the literature, there is a lack of mathematical mechanistic understanding of disintegrating products specifically for a type of disintegration process known as swelling which can be induced by incorporating swelling agents (also known as disintegrants) into the product formulation. Such a model, designated as a product performance model in the literature, not only would be able to predict the disintegration behaviour of granules but also would be the first and main step to optimize the granulation process based on the desired disintegrating features in the product.
It is important to note that a mechanistic product performance model for the swelling driven disintegration of granules should consider all the mechanisms involved in the process. In this study, a new mechanistic disintegration model has been developed, consisting of two linked sub-models. The first sub-model, also known as the single granule swelling model, considers all the mechanisms involved in the swelling driven disintegration, including liquid imbibition, liquid absorption, swelling and breakage for a single granule. For this model, two different scenarios were considered: The first scenario assumes the primary particles in the granule are mono-sized, while the second scenario considers the size distribution of primary particles. Both scenarios can predict important variables such as granule size and primary particle size within the granule, porosity and saturation. In order to obtain the most important variables and reduce the time for validation and the inverse problem, a global sensitivity analysis was applied to the model. The outcome showed that for both scenarios, initial porosity and diffusivity of disintegrant are the most important parameters while for the distributed scenario, the size distribution of disintegrant also plays an important role. To validate the mono-sized model, a specific type of formulation was chosen to isolate the swelling driven disintegration that focused on the disintegrant content. The validation was performed on two sets of formulation using a specially designed flow cell combined with digital optical microscopy that tracked the size of a single granule during disintegration. Through the validation, it was concluded that the concentration of binder in the solution plays an important role in slowing down the disintegration.
In the second part, a lumped based population balance model was developed based on the mono-sized sub-model developed in the first part. The population balance model considers the growth (due to swelling and also erosion from hydrodynamic forces around the granules) and breakage as the only processes in the model. As with the single granule swelling model, global sensitivity analysis was applied to obtain the most important parameters in the model. It was determined that diffusivity of disintegrant was the single most influential parameter in the model. For the validation, a technique known as focused beam reflectance technique (FBRM) combined with an inverse problem method was utilized to obtain the size distribution of disintegrating granules and the released primary particles. The results showed that the model predicts the behaviour of the disintegration for all formulations, and the degree of disintegration increases as the disintegration time increases. Finally, a series of recommendations has been suggested to increase the accuracy of the model, such as combining the model with more detailed mathematical techniques.
