Polymeric delivery formulations of leuprolide with improved efficacy

The present invention relates to a liquid composition for use as a suitable controlled release implant, comprising (a) a biodegradable thermoplastic polyester which is at least substantially insoluble in aqueous medium or body fluid; (b) a unbiologically compatible polar aprotic solvent selected from the group consisting of amine, ester, carbonate, ketone, ether and sulfonyl, wherein the biocompatible polar aprotic solvent is miscible-dispersible in the aqueous medium or body fluid; and (c) contains leuprolide acetate. The present invention also provides a method for preparing the above composition. The invention also relates to the use of a biodegradable thermoplastic polyester, biocompatible polar aprotic solvent and leuprolide for the preparation of a composition, which is able to inject a biodegradable implant into situgaria in a patient when injected and enables the production of a solid biodegradable implant in which an effective amount of biodegradable thermoplastic polyester is present which is substantially insoluble in water or in body fluid; an effective amount of a biocompatible polar aprotic solvent selected from the group consisting of amide, ester, carbonate, ketone, ether and sulfonyl and abiopoiated polar aprotic solvent in a miscible, dispersible, aqueous medium or body fluid; and contains an effective amount of leuprolide acetate. The invention further provides a kit comprising: (a) a first container comprising a composition comprising a biodegradable thermoplastic polyester, which is at least substantially insoluble in aqueous medium or body fluid and comprises a biocompatible polar aprotic solvent and (b) a second container containing leuprolide acetate. The subject invention further comprises a solid implant comprising: (a) a biologically compatible thermoplastic polyester which is essentially insoluble in aqueous medium or body fluid; and (b) leuprolide acetate wherein the solid implant has a solid or gelatinous micropore matrix surrounded by a matrix core. HE which is essentially insoluble in aqueous medium or body fluid; and (b) leuprolide acetate wherein the solid implant has a solid or gelatinous micropore matrix surrounded by a matrix core. HE which is essentially insoluble in aqueous medium or body fluid; and (b) leuprolide acetate wherein the solid implant has a solid or gelatinous micropore matrix surrounded by a matrix core. HE