阿卡布鲁替尼麦酸盐片相比于阿卡布鲁替尼胶囊具有更好的配方优化，因为它们可以在有或无酸还原剂的情况下进行剂量，从而让更多的癌症患者受益。药物产品的溶出度规范是根据药品安全性、药效和体外性能等所有可用信息来确定的。此外，本着为确保所有患者安全和有效的考虑，还开发了基于生理药物动力学的阿卡布鲁替尼麦酸盐片模型，该模型基于此前发表的阿卡布鲁替尼胶囊模型而建立，以确保所提出的药品产品溶出度规范。该模型经过了构建、验证，还用于预测溶出速度低于临床目标的虚拟批次的暴露情况。将曝光预测和PK-PD模型相结合，可以证明所提出的药品产品溶出度规范是可接受的。这些模型的结合使得安全空间更大，而不仅仅考虑生物等效性。

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.