Drug release from injectable depots: two different in vitro mechanisms

Area of Science:

• Polymer science
• Biomaterials science
• Drug delivery systems

Background:

• Poly (lactide-co-glycolide) (PLGA) in benzyl benzoate (BB) can form gels under specific conditions.
• Depot formation is crucial for controlled drug release applications.
• Understanding gelation mechanisms is key to optimizing drug delivery formulations.

Purpose of the Study:

• To investigate the gelation behavior of PLGA/BB solutions.
• To elucidate the mechanism of depot formation in this system.
• To characterize in vitro drug release kinetics and influencing factors.

Main Methods:

• Evaluation of various PLGA polymers in benzyl benzoate.
• Assessment of gel formation upon aging and buffer injection.
• In vitro drug release studies using both base and salt drug forms.
• Rheological property measurements and gel permeation chromatography (GPC) analysis.

Main Results:

• PLGA/BB solutions that gel upon aging also form gel depots in buffer, indicating a distinct mechanism from phase inversion.
• In vitro drug release is governed by diffusion and erosion.
• The base form of the drug is released faster than its salt form due to base-catalyzed hydrolysis.
• Rheological studies show viscosity maxima upon buffer injection, dependent on drug type and concentration.

Conclusions:

• Depot formation in PLGA/BB systems differs from traditional phase inversion methods.
• Drug release is a complex process influenced by polymer properties, drug form, and formulation.
• PLGA/BB formulations offer potential for controlled drug delivery, with tunable release characteristics.