Setting dissolution specifications at the R&D stage is a critical step in pharmaceutical product development. It ensures that the formulation will consistently meet performance expectations and regulatory requirements. Here’s a clear step-by-step guide:
How to Set Dissolution Specifications in R&D
1. Understand the Role of Dissolution
Dissolution testing predicts how the drug will behave in vivo. It is especially important for oral solid dosage forms like tablets and capsules, where dissolution rate can impact bioavailability.
2. Start with the Reference Product
- For generics, the Reference Listed Drug (RLD) or innovator product is the baseline.
- Conduct comparative dissolution studies with the RLD in various media (pH 1.2, 4.5, 6.8).
- Identify the media in which the RLD shows discriminatory power (i.e., differentiates between formulations).
- Match the profile using f2 similarity factor (target: f2 ≥ 50).
3. Use Biopharmaceutics Classification System (BCS) Guidance
- BCS Class I: High solubility and permeability — usually less dissolution-sensitive.
- BCS Class II: Low solubility — dissolution is critical to bioavailability → tighter specs needed.
- Adjust specification based on how dissolution affects in vivo performance.
4. Design Discriminatory Method
- Your dissolution method should detect changes in formulation, process, and API attributes.
- Select a medium and apparatus that reflect real-world performance.
- Include surfactants (e.g., SLS) if needed for poorly soluble drugs.
5. Set a Tentative Specification
Common format for IR tablets:
Not less than 80% (Q) drug release in 30 minutes in selected medium
Adjust based on:
- RLD behavior
- Bioequivalence risk
- Clinical relevance
For MR/ER products: multi-timepoint specs like:
20–40% in 1 hour, 50–70% in 4 hours, NLT 80% in 12 hours
6. Refine Post-BE Study
Once BE is passed, revise specs to reflect actual release behavior of bioequivalent batches.
This becomes the final commercial specification.
7. Align with Regulatory Expectations
Follow regional guidelines:
- USFDA: SUPAC & dissolution guidance
- EMA: Guideline on the investigation of bioequivalence
- WHO: Stability and QC specs for multisource products
Best Practice Tip:
Always justify your specification scientifically — through comparative data, risk assessment, and in vitro–in vivo correlation (IVIVC) if available.
Read also:
- The f2 Similarity Factor in Dissolution
- What Should be Considered During Specification Setting?
- Impurity Specification Across Different Regulatory Bodies
Resource Person: Moinuddin Syed. Ph.D, PMP®