Injectable testosterone PLGA microsphere with different characteristics: effect of preparation method (paddle mixing versus microfluidic device)

Abstract

The purpose of this study was to compare the characteristics of testosterone polylactic-co-glycolic (PLGA) microspheres prepared by a paddle mixer or microfluidics device. The comparison was conducted by not only in vitro evaluation but also in vivo evaluation which has not been reported up to date. We discovered that, among the steps in microsphere preparation, the solvent removal process strongly impacted drug content, particle size and surface morphology. Spectroscopic measurements suggested that molecular interactions and crystallinity of the drug incorporated in the microspheres differed. For the drug release profile, although both mixer- and microfluidics-prepared samples showed similar sustained release of the incorporated drug for approximately one month in vitro, they exhibited different plasma concentration profiles in vivo. Together, our findings show that the preparation process, especially the solvent removal process, may affect the physicochemical characteristics of testosterone PLGA microspheres, leading to different in vivo performance.

Graphical Abstract

Keywords:

• Polylactic-co-glycolic acid
• microsphere
• microfluidics
• emulsification
• testosterone

Acknowledgments

The authors thank Mr. Koichi Yonezawa, Mr. Hiroyuki Moriguchi and Mr. Hideki Isomura (Astellas Pharma Inc.) for their technical contribution to plasma concentration quantification; Mr. Shinichi Ogino for his technical contribution to in vivo studies; Dr. Ryo Mizoguchi for his analytical advice on X-ray diffraction measurement; and Mr. Naoki Takahashi for his technical support in FT-IR measurement.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was funded by Astellas Pharma Inc.