A cocrystal-based long-acting injectable suspension platform enables tunable drug release

Area of Science:

• Pharmaceutical Science
• Materials Science
• Drug Delivery

Background:

• Long-acting injectables are crucial for patient adherence in chronic disease management.
• Precise control over drug release from injectables remains a significant challenge.
• Pharmaceutical cocrystals offer a versatile strategy for modulating drug release kinetics.

Purpose of the Study:

• To develop a cocrystal-based long-acting injectable suspension platform with tunable drug release.
• To investigate the impact of coformer chain length on cocrystal properties and drug release.
• To establish a scalable and clinically translatable drug delivery system.

Main Methods:

• Aripiprazole cocrystals were synthesized using even-chain saturated monocarboxylic acids (C10-C24) via solution crystallization.
• Cocrystals were formulated into wet-milled suspensions for intramuscular administration.
• Pharmacokinetic studies were conducted in rats and beagles to evaluate drug exposure and release profiles.

Main Results:

• Isostructural aripiprazole cocrystals exhibited systematic physicochemical property variations with increasing fatty acid chain length.
• In vivo studies demonstrated chain length-dependent pharmacokinetics in rats.
• A lead cocrystal suspension in beagles achieved drug exposures comparable to a clinical combination regimen.

Conclusions:

• This work presents a scalable, tunable, and clinically translatable long-acting injectable system using cocrystals.
• The developed platform offers adjustable drug release properties for improved chronic disease management.
• This establishes a rational approach for developing cocrystal-based long-acting injectables.