Comparative in vitro release and clinical pharmacokinetics of leuprolide from Luphere 3M Depot, a 3-month release formulation of leuprolide acetate

Abstract

A 3-month depot formulation of leuprolide acetate (Luphere 3M Depot) with a mean microsphere diameter of 22.3 μm was prepared aseptically by spray-drying glacial acetic acid solution of the drug and polylactic acid, and lyophilization in a d-mannitol solution. The encapsulation efficiency and loading content of the drug in the Luphere 3M Depot were 94.7% and 9.92% (w/w), respectively. The in vitro release of leuprolide from the depot was substantially delayed and the release profile was similar to that of Lucrin Depot (Abbott Korea, Korea). The safety and pharmacokinetics of leuprolide were investigated over a period of 42 days in 20 prostate cancer patients following a subcutaneous injection of Luphere 3M or Lucrin Depot suspensions (leuprolide acetate dose of 11.25 mg) in a multi-center, randomized, single dose, parallel study. Both formulations were well tolerated by the patients and no serious adverse effects were observed during and after the study. No significant differences were observed in the maximum serum concentration (Cmax) and area under the curve (AUClast) of leuprolide between the two formulations. The results suggest comparable safety and efficacy profiles of Luphere 3M Depot and Lucrin Depot in clinical situations.