Key Characteristics:

• Sensitive to critical material attribute changes (e.g., excipient levels, particle size) within meaning full ranges.
• Sensitive to formulation changes (e.g., excipient levels, particle size) within range of ± 10-20% from their theoretical values
• Responsive to process variations (e.g., compression force, mixing time) within range of ± 10-20% from their theoretical values
• Should capable to show in vitro differences between bio compliant and non-bio compliant test drug product batches
• Capable of detecting stability-related degradation
• Predictive of in vivo behavior, especially for poorly soluble drugs

Why Is It Important in ANDA/NDA Applications?

In Abbreviated New Drug Applications (ANDA) and New Drug Applications (NDA), dissolution discrimination plays a pivotal role.

For ANDA filings, QC dissolution test method must be discriminatory enough. For NDAs, it helps define the product’s critical quality attributes and supports robust Quality by Design (QbD) strategies.

FDA Perspectives and Quotes from Guidances

The U.S. Food and Drug Administration (FDA) emphasizes the importance of discriminatory dissolution methods across multiple guidances:

“The discriminatory power of the dissolution method is the method’s ability to detect changes in the drug product.” — FDA Guidance on Dissolution Testing of Immediate Release Solid Oral Dosage Forms

“A dissolution method with suitable discriminating power is preferred to indicate any possible changes in the quality of the product before in vivo performance is affected.” — Discriminatory Dissolution Method Development for Etoricoxib Tablets

“The FDA and EMA guidance documents... accept alternative approaches provided that the dissolution method has sufficient discriminatory power to assess the critical quality attributes (CQAs) of a drug product.” — Dissolution Method Development for Regulatory Approval

These quotes underscore the regulatory expectation that dissolution methods must not only be reproducible but also sensitive enough to detect formulation and process changes that could impact therapeutic efficacy.

How to Develop a Discriminatory Dissolution Method

Developing a robust discriminatory method involves:

• Understanding API properties (e.g., solubility, pKa)
• Selecting appropriate media (pH range, surfactants)
• Optimizing apparatus and conditions (paddle vs. basket, rpm, volume)
• Conducting risk assessments and design of experiments (DoE)
• Validating method reproducibility and robustness

The FDA recommends using f2 similarity factor and sink condition evaluations to assess method performance. A method should fail to show similarity when critical changes are introduced—this confirms its discriminatory nature.

Whether you have adopted the Compendial Dissolution method or OGD’s database method, it is required to justify the suitability of the dissolution method for proposed product. As each formulation is different, the recommendation in USP/FDA dissolution method database may not be suitable to for proposed drug product.

Whether you're preparing an ANDA, NDA, or teaching the next generation of pharmaceutical experts, understanding and applying discriminatory dissolution principles will elevate your work—and your impact.

Stay tuned and keep checking ISAZI Academy Blog for more such interesting insightful topics.

Disclaimer This and other blogs reflects the views of the author and should not be construed to represent any Agency’s views or policies. We are not liable for any damages, losses, or consequences that may arise from the use of this information or referencing it. The information is provided for academic interest and general information purpose only. Readers must ensure compliance with all applicable regulations and guidelines.