Self-aggregating long-acting injectable microcrystals.

Area of Science:

• Biomaterials Science
• Pharmaceutics
• Drug Delivery Systems

Background:

• Injectable drug depots improve medication adherence via dose simplification.
• Patient acceptance of injectables is influenced by needle gauge and associated discomfort.
• High drug loading in injectables is crucial for sustained release and reduced injection volume/discomfort.

Purpose of the Study:

• To develop a novel injectable formulation, SLIM (self-aggregating long-acting injectable microcrystals), to address patient comfort and drug delivery efficiency.
• To achieve high drug loading and enable injection with low-profile needles (<25 G).
• To investigate the mechanism of self-aggregation and its impact on drug release kinetics.

Main Methods:

• Formulation of drug microcrystals designed for self-aggregation in the subcutaneous space.
• Characterization of the SLIM formulation, including drug loading capacity and polymer-to-drug ratio (0.0625:1 w/w).
• In vitro and in vivo studies to assess self-aggregation driven by solvent exchange and evaluate long-term drug release in rodents.

Main Results:

• SLIM forms a monolithic implant with minimal polymer excipient, allowing for high drug loading (293 mg/ml).
• Self-aggregation is confirmed to be solvent-exchange-dependent, with slower-exchanging solvents leading to denser implants.
• Enhanced long-term drug release was observed in vivo due to the self-aggregation mechanism.

Conclusions:

• SLIM technology facilitates the development of injectable formulations with high drug loading and low polymer content.
• The self-aggregation property enables injection via small-gauge needles, improving patient comfort.
• SLIM holds promise for cost-effective, long-acting injectable therapies, particularly for applications like contraceptives.