API particle size governs in situ forming implant formation, microstructure evolution and performance

Area of Science:

• Drug Delivery Systems
• Materials Science
• Pharmaceutical Sciences

Background:

• In situ forming implants (ISFIs) are long-acting injectable (LAI) systems forming implants upon injection.
• No generic ISFI products are currently available, highlighting a need to understand critical quality attributes (CQAs).
• The influence of the active pharmaceutical ingredient (API) on ISFI performance is not well-defined.

Purpose of the Study:

• To investigate the impact of API particle size and morphology on risperidone ISFI formation and in vitro release.
• To elucidate how API characteristics influence implant microstructure, water uptake, and polymer degradation.
• To support the development of generic and innovator ISFI products by defining key formulation attributes.

Main Methods:

• Formulations of risperidone ISFIs with varying API particle sizes were prepared.
• Implant microstructure was characterized using laser scanning confocal microscopy (LSCM) and an adhesive thin-film technique.
• Water uptake, polymer degradation, and in vitro drug release were extensively evaluated.

Main Results:

• API particle size was found to be a critical factor influencing ISFI microstructure.
• Significant differences in water uptake and polymer degradation rates were observed based on API particle size.
• In vitro drug release profiles were demonstrably affected by the API particle size and resulting implant characteristics.

Conclusions:

• API particle size is a crucial determinant of ISFI performance, affecting microstructure, degradation, and drug release.
• This study provides essential insights into the CQAs of ISFIs, particularly concerning API attributes.
• The findings will aid in the rational design and development of future generic and innovator ISFI products.