Injectable testosterone PLGA microsphere with different characteristics: effect of preparation method (paddle mixing...

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Pharmaceutical Technology

Background:

• Testosterone replacement therapy often utilizes long-acting injectable formulations.
• Polylactic-co-glycolic acid (PLGA) microspheres are a common drug delivery system for sustained release.
• Optimizing microsphere preparation is crucial for predictable in vivo drug performance.

Purpose of the Study:

• To compare testosterone PLGA microspheres prepared using a paddle mixer versus a microfluidics device.
• To evaluate the impact of preparation methods on in vitro and in vivo characteristics.
• To investigate the role of the solvent removal process in microsphere properties.

Main Methods:

• Preparation of testosterone PLGA microspheres using paddle mixer and microfluidics.
• In vitro characterization including drug content, particle size, and surface morphology analysis.
• In vitro drug release studies and in vivo pharmacokinetic evaluations in animal models.

Main Results:

• Solvent removal process critically affected drug content, particle size, and surface morphology.
• Spectroscopic analysis revealed differences in drug crystallinity and molecular interactions within microspheres.
• Both methods showed similar in vitro sustained release for one month, but distinct in vivo plasma concentration profiles.

Conclusions:

• The preparation method, particularly solvent removal, significantly impacts testosterone PLGA microsphere physicochemical properties.
• Differences in microsphere characteristics due to preparation can lead to varied in vivo drug performance and release kinetics.
• This study highlights the importance of optimizing manufacturing processes for consistent and effective long-acting injectable drug formulations.