Enhancing Chemical Stability and Bioavailability of Aneratrigine Capsules via Dry Granulation: Addressing Stability...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Formulation Development

Background:

• Aneratrigine, a selective Nav1.7 inhibitor, exhibits poor aqueous solubility in acidic conditions, limiting oral bioavailability.
• Initial attempts at oral formulation using sodium bicarbonate (NaHCO3) for pH modulation faced stability issues during wet granulation.

Purpose of the Study:

• To develop a stable and scalable oral formulation for aneratrigine.
• To overcome the challenges of poor solubility and NaHCO3-induced degradation in the formulation.

Main Methods:

• Development of a capsule formulation incorporating sodium bicarbonate (NaHCO3) for in situ pH modulation.
• Comparison of wet granulation and dry granulation techniques to address stability issues.
• Scalability assessment of the dry granulation process across different batch sizes.

Main Results:

• Dry granulation successfully minimized heat and moisture exposure, preventing NaHCO3 decomposition and subsequent degradation.
• The optimized dry granulation process was scalable from laboratory to commercial batches, maintaining chemical integrity.
• The final formulation demonstrated enhanced stability (total impurities < 0.05%) and improved dissolution (>80% at 30 min, pH 4.0).

Conclusions:

• A robust manufacturing platform was established for alkalizer-containing formulations, overcoming heat and moisture sensitivity.
• The developed formulation facilitates the advancement of aneratrigine to Phase 2a clinical trials.
• This approach serves as a model for formulating other heat- and moisture-sensitive compounds.