One- and three-month release injectable microspheres of the LH-RH superagonist leuprorelin acetate

Adv Drug Deliv Rev. 1997 Oct 13;28(1):43-70. doi: 10.1016/s0169-409x(97)00050-1.


The biodegradable polymers poly(lactic/glycolic acid) (PLGA) and poly(lactic acid) (PLA) were used as wall materials in the preparation of microspheres (msp) containing the LH-RH superagonist leuprorelin (leuprolide) acetate. A novel W/O/W emulsion-solvent evaporation method was devised for the preparation of msp containing this water-soluble peptide. This method achieved high entrapment efficiency and sustained drug release over a long period predominantly due to polymer bioerosion. The msp are fine microcapsules with polycores containing the peptide at a high concentration and are easily injectable through a conventional fine needle. Leuprorelin msp made with PLGA(75/25)-14,000 or PLA-15,000 released the drug in a zero-order fashion, maintained constant serum drug levels and attained persistent objective suppression of the pituitary-gonadal system ('chemical castration') over 1 or 3 months after i.m. or s.c. injection into animals. These results indicate that depot formulations may be potentially useful in the therapy of endocrine diseases in humans. In this paper, studies on the formulation, drug release and pharmacological effects in animals for these leuprorelin depot formulations are reviewed.