The Development of a Stable Peptide-Loaded Long-Acting Injection Formulation through a Comprehensive Understanding of...

Area of Science:

• Pharmaceutical Science
• Drug Delivery Systems
• Biotechnology

Background:

• Quality by Design (QbD) is a systematic pharmaceutical development approach.
• Understanding peptide degradation is crucial for stable formulations.
• Long-acting injectable (LAI) formulations offer advantages in drug delivery.

Purpose of the Study:

• To develop a stable peptide-loaded long-acting injectable (LAI) formulation using Quality by Design (QbD).
• To identify and control critical material attributes (CMAs) and critical process parameters (CPPs) for peptide stability.
• To achieve in vivo long-acting release of a peptide drug.

Main Methods:

• Forced degradation studies to elucidate peptide degradation pathways (hydrolysis, oxidation).
• Risk assessment to identify CMAs and CPPs linked to critical quality attributes (CQAs).
• Development and evaluation of LAI formulations using PLGA-based in situ gel.
• Pharmacokinetic studies in rats to assess in vivo performance.

Main Results:

• Acid hydrolysis and oxidation identified as primary degradation pathways for peptide ACTY116.
• Effective control strategies were developed for LAI formulations, enhancing CQAs.
• The most stable LAI formulation demonstrated successful in vivo long-acting release in rats.
• PLGA-based in situ gel proved effective in stabilizing peptide ACTY116.

Conclusions:

• The QbD approach successfully yielded a stable peptide-loaded LAI formulation.
• The developed LAI formulation addresses peptide chemical instability and achieves desired in vivo release.
• PLGA-based in situ gels are a promising platform for stabilizing various molecules in LAI formulations.