In dissolution testing, the focus is usually on ensuring the minimum drug release (e.g., "not less than 80% in 30 minutes") to guarantee therapeutic efficacy. An upper limit is not explicitly set for several reasons:
1. Complete Drug Release: The goal of dissolution is to confirm sufficient drug release (close to 100%) for bioavailability.
2. Analytical and Manufacturing Variability: Slight variations above 100% may occur due to assay variability, overfill, or excipient effects.
3. Focus on Patient Safety: In dissolution tests, higher-than-expected release rarely poses a direct risk since the drug is tested in controlled conditions.
However, when dissolution results exceed acceptable thresholds significantly, a systematic investigation is required:
Steps to Take When Dissolution Results Are High
1. Reconfirm the Results:
- Repeat the dissolution test.
- Verify equipment calibration and analytical accuracy (HPLC, UV, etc.).
2. Review the Analytical Method:
- Check the system suitability, media conditions (pH, volume, temperature), and assay performance.
3. Investigate the Manufacturing Process:
- Assess content uniformity and potential overfilling of the active pharmaceutical ingredient (API).
- Review raw material quality and excipient impact.
4. Analyze Possible Interferences:
- Look for excipient interactions or drug degradation products causing higher readings.
5. Root Cause Analysis (RCA):
- Use tools like the Ishikawa diagram to pinpoint the root cause of the issue.
6. Implement Corrective and Preventive Actions (CAPA):
- Correct the immediate problem.
- Apply preventive measures to avoid recurrence.
Key Takeaway:
While an upper limit isn’t explicitly defined in dissolution testing, significantly high results must be investigated thoroughly to maintain product quality, regulatory compliance, and most importantly, patient safety.
Read also:
- What is the Infinity Spin in Dissolution?
- What is Q value in Dissolution?
- Frequently Asked Questions and Answers on Out of specification (OOS)
