In vitro and in vivo evaluations of a 3-month sustained-release microsphere depot formulation of leuprolide acetate

• Published in: Journal of pharmaceutical investigation Vol. 52; no. 1; pp. 129 - 138
• Main Authors: Kim, Gwan-Young, Kim, Jin-Ho, Lee, Taeho, Bae, Byoung-Chan, Baik, Hyejeong, Kim, Taeheon, Kim, Junsik, Kang, Dong Wook, Kim, Ju Hee, Kim, Dahan, Cho, Hea-Young, Kim, Dae-Duk
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.01.2022; 한국약제학회
• Subjects: Biomedical and Life Sciences; Biomedicine; Original Article; 약학; 3-Month depot; Pharmacodynamics; Microsphere; Sustained-release; Pharmacokinetics; Leuprolide acetate
• ISSN: 2093-5552; 2093-6214
• DOI: 10.1007/s40005-021-00551-x

Purpose The aim of this work was to evaluate a new polylactic acid microsphere depot formulation (Leuprolide Depot 3 M) prepared by a water-in-oil-in-water emulsion/solvent evaporation method. Methods The physical properties of the microspheres, including particle size and drug encapsulation efficiency, were characterized. The accelerated and long-term in vitro release profiles were examined. Pharmacokinetic and pharmacodynamic studies were conducted in male beagle dogs after a single subcutaneous injection of the microspheres at 11.25 mg/animal leuprolide acetate by measuring the plasma leuprolide and testosterone levels, respectively. Results Leuprolide Depot 3 M was spherical in shape with a smooth surface and showed an average diameter of 17.83 μm and a drug loading content of 7.58% (w/w). These properties were comparable to those of Lupron Depot 30 mg, a commercial product. In vitro release of leuprolide at 37 °C from both formulations was sustained for up to 126 days and showed a similarity factor (f2) of 51.0. In the pharmacokinetic study, the plasma leuprolide concentration after subcutaneous injection of Leuprolide Depot 3 M or Lupron Depot 30 mg remained at approximately 0.1 ng/mL for up to 98 days. There were no significant differences in the pharmacokinetic parameters between the two formulations. Moreover, the plasma testosterone level was effectively suppressed to less than 0.5 ng/mL until the end of the evaluation. Conclusion These results suggest that Leuprolide Depot 3 M and Lupron Depot 30 mg are expected to have comparable efficacy profiles in clinical settings, which should be confirmed in further clinical studies.