Discriminative Dissolution Development and Validation of Poorly Soluble Drugs Using Method Operable Design Region

Establishing reliable and discriminative dissolution methods is critical for maintaining the quality and batch consistency of poorly soluble drug formulations—a process often hindered by conventional development techniques. This review emphasizes the transformative benefits of implementing structured Quality by Design (QbD) and Analytical QbD (aQbD) methodologies. By employing Design of Experiments (DoE), a Method Operable Design Region (MODR) can be optimized to guarantee method robustness. Additionally, implementing systematic evaluation protocols—such as defining a Method Discriminative Design Region (MDDR)—ensures the method’s ability to detect critical variations in formulation and manufacturing processes. Adopting these advanced, science- and risk-based strategies provides a streamlined and dependable framework for creating fit-for-purpose dissolution techniques. Such an approach not only deepens process understanding but also ensures sustained product quality for complex, poorly soluble drugs across their entire lifecycle.