Acalabrutinib Maleate Tablets: The Physiologically Based Biopharmaceutics Model behind the Drug Product Dissolution Specification.

Acalabrutinib maleate tablets correspond to an improved formulation compared to acalabrutinib capsules as they can be dosed with and without acid reducing agents and therefore benefit more cancer patients. The dissolution specification for the drug product was determined using all the information available on the drug safety, efficacy, and in vitro performance. In addition, a physiologically based biopharmaceutics model was developed for acalabrutinib maleate tablets on the back of a previously published model for acalabrutinib capsules to establish that the proposed drug product dissolution specification would ensure safe and effective products for all patients including those under acid reducing agent treatment. The model was built, validated, and used to predict the exposure of virtual batches where the dissolution was slower than that of the clinical target. A combination of exposure prediction and the use of a PK-PD model allowed it to be demonstrated that the proposed drug product dissolution specification was acceptable. This combination of models enabled a larger safe space than would have been granted by consideration of bioequivalence only.