Development and Validation of a Discriminatory Dissolution Model for an Immediately Release Dosage Form by DOE and Statistical Approaches.

A discriminatory dissolution model was built through DOE with multivariate analysis of variance (MANOVA) and multiple linear regression (MLR) modeling to assess dissolution operational space for a highly water soluble immediate-release solid dosage drug product. The dissolution was utilized in the following five aspects: (1) understand the impact of individual variables and their interactions on dissolution performance through effect analysis; (2) explain the lack of discriminatory power of the initial dissolution condition used in early phase development by prediction profiler; (3) predict discriminatory dissolution operational space to differentiate photo degraded drug products from control with contour profiler analysis; (4) validate by the external experimental data acquired with the initial nondiscriminatory dissolution condition and the predicted discriminatory dissolution condition, followed by model independent statistical analysis (e.g., f2); and (5) establish correlation of the discriminatory dissolution with disintegration. The selected discriminatory dissolution method was validated by demonstrating accuracy, precision and linearity, specificity, repeatability, intermediate precision, stability, filter verification, and robustness.