Discriminative Dissolution Method Development Through an aQbD Approach

Using a one-factor-at-a-time approach for dissolution method and discrimination analysis can be time-consuming and may not yield the optimal and discriminative method. To address this, we have developed a two-stage workflow for the dissolution method development followed by demonstration of discrimination power through an analytical Quality by Design (aQbD) approach. In the first stage, an optimal dissolution method was achieved by determining the method operable design region (MODR) through a design of experiment study of the high-risk method-related parameters. In the second stage, we established a Formulation-Discrimination Correlation Diagram strategy to examine the method discrimination capability, through which one can determine the method discriminative design region (MDDR) and visualize the impact of each formulation parameter and their interactions on dissolution. The application of aQbD principles into a workflow provides a scientific-driven guidance for robust method development and demonstrating discrimination power for dissolution methods.

Materials

The drug substances (Biogen, Cambridge, MA), silicified microcrystalline cellulose (SMCC 90, JRS Pharma, Patterson, NY), croscarmellose sodium (CCM-Na, Merck KGaA, Billerica, MA), colloidal silicon dioxide (Aerosil 200, Evonik, Sanford, ME), magnesium stearate (MgSt, Spectrum, New Brunswick, NJ), sodium phosphate (Thermo Fisher Scientific, Fair Lawn, NJ), and sodium hydroxide (LabChem, Zelienople, PA), were used as received. Acetonitrile, methanol, isopropanol, ammonium hydroxide solution, and ammonium acetate were purchased from Fisher Chemical (Fair Lawn, NJ). All solvents were of HPLC grade.

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Chen, H., Wang, R. & McElderry, JD. Discriminative Dissolution Method Development Through an aQbD Approach. AAPS PharmSciTech 24, 255 (2023).
https://doi.org/10.1208/s12249-023-02692-8