Dissolution or disintegration - substitution of dissolution by disintegration testing for a fixed dose combination...

Area of Science:

• Pharmaceutical Sciences
• Drug Product Development
• Quality Control

Background:

• International Council for Harmonisation (ICH) guideline Q6A permits replacing dissolution testing with disintegration testing under specific conditions.
• Establishing a relationship between dissolution and disintegration is crucial for this substitution.
• Empagliflozin and linagliptin fixed-dose combination (FDC) tablets require evaluation for this testing strategy.

Purpose of the Study:

• To establish the relationship between dissolution and disintegration for empagliflozin and linagliptin FDC tablets.
• To demonstrate that disintegration is the rate-limiting step in the drug release process.
• To support the replacement of dissolution testing with disintegration testing per ICH Q6A.

Main Methods:

• Investigated the contribution of film-coated tablet disintegration to active ingredient release.
• Correlated mean disintegration times with mean dissolution rates at selected time points.
• Utilized statistical analysis and bioavailability study data to set disintegration time specifications.

Main Results:

• Disintegration into primary particles was identified as the rate-limiting step for dissolution.
• A direct correlation between disintegration times and dissolution rates was established.
• The disintegration test method demonstrated comparable discriminatory power to dissolution testing.

Conclusions:

• The study successfully established the dissolution-disintegration relationship for the FDC tablet.
• Data support the replacement of dissolution testing with disintegration testing for empagliflozin and linagliptin FDC tablets, aligning with ICH Q6A.
• A clinically relevant disintegration time specification was successfully established.