Insights into development of long-acting injectable suspensions

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Biopharmaceutics

Background:

• Long-acting injectable (LAI) suspensions are valuable for chronic disease management, improving adherence and reducing dosing frequency.
• Despite benefits, LAI suspension development faces challenges in understanding complex release mechanisms, defining critical quality attributes (CQAs), and establishing robust in vitro-in vivo correlations (IVIVCs).

Purpose of the Study:

• To provide a comprehensive review of the current landscape of LAI suspension development.
• To highlight recent advancements and identify challenges and future research directions in LAI suspension formulation and regulatory approval.

Main Methods:

• In-depth analysis of market trends, therapeutic uses, regulatory guidelines, manufacturing processes, and key formulation CQAs.
• Review of advancements in physicochemical characterization, in vitro release testing, IVIVC, and physiologically based pharmacokinetic (PBPK) modeling.
• Emphasis on the impact of particle characteristics and depot formation on drug release and novel in vitro methods.

Main Results:

• LAI suspensions present significant pharmaceutical opportunities but face hurdles in development due to complex release and undefined CQAs.
• Recent progress includes enhanced characterization techniques, novel in vitro release assays, and the development of IVIVC and PBPK models.
• Particle size, agglomeration, and depot formation are critical factors influencing drug release kinetics.

Conclusions:

• Overcoming regulatory and technical barriers requires innovative approaches, including biorelevant release methods and mechanistic modeling.
• Advancements in understanding and predicting drug release are crucial for successful LAI suspension development and approval.
• This review offers insights for scientists and regulators to advance the field of LAI suspension technology.