Polymeric delivery formulations of leuprolide with improved efficacy

A flowable composition suitable for use to form an in situ, single body controlled release implant, the composition comprising a non-aqueous, liquid solution of:

• (a) a biodegradable thermoplastic chain extended copolymer of lactide and glycolide including hexane diol as a chain extender;
• (b) N-methyl-2-pyrrolidone;
• and (c) leuprolide acetate;
• wherein,
• the copolymer has a weight average molecular weight of about 15,000 to about 45,000, and is present in the composition at about 30 wt % to about 50 wt %;
• the N-methyl-2-pyrrolidone is present in the composition at about 45 wt % to about 70 wt %;
• and,
• the leuprolide acetate is present in the composition at least at about 2 wt %.

A method of reducing serum testosterone levels in a male human comprising injecting subcutaneously into the male human about 0.2 ml to about 0.5 ml of a flowable composition comprising a non-aqueous, liquid solution of:

• (a) a biodegradable thermoplastic chain extended copolymer of lactide and glycolide including hexane diol as the chain extender;
• (b) N-methyl-2-pyrrolidone;
• and (c) leuprolide acetate;
• wherein
• the chain extended copolymer has a weight average molecular weight of about 15,000 to about 45,000 and is present in the composition at about 30 wt % to about 50 wt %;
• the N-methyl-2-pyrrolidone is present in the composition at about 45 wt % to about 70 wt %;
• and,
• the leuprolide acetate is present in the composition at least at about 2 wt %;
• the flowable composition forms in situ a monolithic solid implant of a microporous matrix of a core surrounded by a skin within a body tissue of the male human.