Microsphere formulations comprising nalmefene and methods for making and using the same

A microsphere formulation comprising polymer microspheres, each polymer microsphere comprising:

• (i) nalmefene;
• and
• (ii) a biodegradable polymer comprising an acid end-capped poly (D,L-lactide-co-glycolide) polymer having an inherent viscosity (IV) of between about 0.6 dL/g and 0.8 dL/g,
• wherein each polymer microsphere comprises a drug load of greater than 25 wt/wt %, and wherein the polymer microspheres have an average particle size of between about 10 μm to about 40 μm (D50), for use as a medicament for the treatment of alcohol and/or opioid dependence,
• wherein the formulation releases nalmefene at an amount of at least 0.5 ng/mL over a sustained period of at least 60 days.

A nalmefene formulation, comprising:

• a. a microsphere comprising poly(lactic-co-glycolic acid) (PLGA) with a ratio of lactide to glycolide of between 80:20 to 90:10;
• and
• b. a nalmefene base loaded into the microsphere at an amount of at least 20% w/w, relative to the microparticle,
• wherein the formulation releases nalmefene at an amount of at least 0.5 ng/ml over a sustained period of at least 80 days.

A nalmefene formulation, comprising:

• a. a microsphere comprising poly(lactic-co-glycolic acid) (PLGA) with a ratio of lactide to glycolide of between 82:18 to 88:12, a molecular weight of between 50-80 kDa, and an average particle size of between about 60 μm to about 100 μm;
• and
• b. a nalmefene base having an average particle size of about 2 μm to about 5 μm, loaded into the microsphere at an amount of at least 30% w/w, relative to the microsphere,
• wherein the formulation releases nalmefene at an amount of at least 1.0 ng/ml over a sustained period of at least 90 days.