Injectable naltrexone microsphere compositions and their use in reducing consumption of heroin and alcohol
AssigneeSouthern Research Institute
InventorsThomas R. Tice, Jay K. Staas, Teresa M. Ferrell
Life of this patent
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Abstract
An injectable slow-release naltrexone formulation is provided comprising naltrexone in a poly(D,L-lactide) matrix with a small amount of residual ethyl acetate. Upon intramuscular injection of the composition, naltrexone is released in a controlled manner over an extended period of time. The composition finds use in the treatment of heroin addicts and alcoholics to reduce consumption of the abused substances.
Claims26
A microsphere composition comprising:
- a naltrexone free base in an amount in the range of 15 to 50 weight %;
- a poly(D,L-lactide) as a matrix;
- a residual amount of ethyl acetate that is less than about 3 weight %, wherein said composition is capable of providing over a period of at least 28 days a physiologically effective level of naltrexone to reduce the consumption of at least one of heroin and alcohol when administered intramuscularly in a mammal, and wherein at least 90 weight % of said microsphere composition comprises microspheres having a diameter in the range of 20 to 100 μm.
A microsphere composition comprising:
- a naltrexone free base in an amount in the range of 15 to 25 weight %;
- a poly(D,L-lactide) as a matrix, wherein said poly(D,L-lactide) has an inherent viscosity in the range of about 0.3 to 0.4 dL/g;
- less than about 3 weight % ethyl acetate, wherein said composition is capable of providing over a period of at least 28 days a physiologically effective level of naltrexone to reduce the consumption of at least one of heroin and alcohol when administered intramuscularly in a mammal, and wherein at least 90 weight % of said microsphere composition comprises microspheres having a diameter in the range of 20 to 100 μm.
A microsphere composition comprising:
- a naltrexone free base in an amount in the range of 35 to 45 weight %;
- a poly(D,L-lactide) as a matrix, wherein said poly(D,L-lactide) has an inherent viscosity in the range of about 1.0 to 1.1 dL/g;
- less than about 3 weight % ethyl acetate, wherein said composition is capable of providing over a period of at least 28 days a physiologically effective level of naltrexone to reduce the consumption of at least one of heroin and alcohol when administered intramuscularly in a mammal, and wherein at least 90 weight % of said microsphere composition comprises microspheres having a diameter in the range of 20 to 100 μm.
A microsphere composition comprising:
- 35 to 45 weight % naltrexone having a poly(D,L-lactide) matrix wherein said composition is capable of releasing about 10 to 40% per week of the initial amount of said naltrexone in said microsphere composition into a human subject over a 4-week period, while maintaining a therapeutic dosage of at least about 1 ng/mL during said 4-week period.
A method of making a plurality of naltrexone poly(D,L-lactide) microspheres, said method comprising:
- preparing an approximately 2 to 7 weight % poly(D,L-lactide) polymer solution with ethyl acetate as the solvent;
- combining naltrexone free base with said polymer solution to produce a naltrexone dispersed phase containing approximately 2 to 3 weight % naltrexone;
- preparing approximately a 2 weight % of poly(vinyl alcohol) solution in water and adding ethyl acetate to produce a poly(vinyl alcohol) continuous phase;
- combining said naltrexone dispersed phase with said polyvinyl alcohol continuous phase to produce an emulsion that contains microdroplets comprising naltrexone, ethyl acetate and poly(D,L-lactide);
- and
- contacting said emulsion with an extraction water phase whereby said plurality of naltrexone poly(D,L-lactide) microspheres are obtained.
A method of microencapsulating naltrexone with poly(D,L-lactide) to form naltrexone poly(D,L-lactide) microspheres, said method comprising
- preparing approximately a 2 to 7 weight % of poly(D,L-lactide) polymer solution with naltrexone free base and ethyl acetate as the solvent;
- preparing approximately a 2 weight % of poly(vinyl alcohol) solution in water and adding ethyl acetate to produce a poly(vinyl alcohol) continuous phase;
- combining said polymer solution with said poly(vinyl alcohol) continuous phase so that an emulsion which contains microdroplets comprising naltrexone, poly(D,L-lactide) and ethyl acetate is obtained;
- and
- contacting said emulsion with an extraction water phase whereby said naltrexone poly (D,L-lactide) microspheres are obtained.
Dependencies are inferred from the claim text.