Buccal, polar and non-polar spray containing testosterone
Buccal aerosol sprays or capsules using polar and non-polar solvent have now been developed which provide testosterone for rapid absorption through the oral mucosa, resulting in fast onset of effect. The buccal polar compositions of the invention comprise formulation I: aqueous polar solvent, testosterone or a pharmaceutically acceptable ester thereof, and optional flavoring agent; formulation II: aqueous polar solvent, testosterone or a pharmaceutically acceptable ester thereof, optionally flavoring agent, and propellant; formulation III: non-polar solvent, testosterone or a pharmaceutically acceptable ester thereof, and optional flavoring agent; and formulation IV: non-polar solvent, testosterone or a pharmaceutically acceptable ester thereof, optional flavoring agent, and propellant; formulation V: a mixture of a polar and a non-polar solvent, testosterone or a pharmaceutically acceptable ester thereof, and optional flavoring agent; formulation VI: a mixture of a polar and a non-polar solvent, testosterone or a pharmaceutically acceptable ester thereof, optional flavoring agent, and propellant.
1 . An oral spray composition for transmucosal administration of testosterone or a pharmaceutically acceptable ester thereof comprising: testosterone or a pharmaceutically acceptable ester thereof in an amount of between 0.1 and 25 percent by weight of the total composition; a polar solvent in an amount between 10 and 97 percent by weight of the total composition; and a propellant in an amount between 2 and 10 percent by weight of the total composition, wherein said propellant is a C 3 to C 8 hydrocarbon of linear or branched configuration.
2 . The composition of claim 1 , further comprising a taste mask and/or flavoring agent in an amount between 0.05 and 10 percent by weight of the total composition.
3 . The composition of claim 2 , wherein the polar solvent is present in an amount between 20 and 97 percent by weight of the total composition, the testosterone or a pharmaceutically acceptable ester thereof is present in an amount between 0.1 and 15 percent by weight of the total composition, the propellant is present in an amount between 2 and 5 percent by weight of the composition, and the taste mask and/or flavoring agent is present in an amount between 0.1 and 5 percent by weight of the total composition.
4 . The composition of claim 3 , wherein the polar solvent is present in an amount between 25 and 97 percent by weight of the total composition, the testosterone or a pharmaceutically acceptable ester thereof is present in an amount between 0.2 and 25 percent by weight of the total composition, the propellant is present in an amount between 2 and 4 percent by weight of the composition, and taste mask and/or flavoring agent is present in an amount between 0.1 and 2.5 percent by weight of the total composition.
5 . The composition of claim 1 , wherein the polar solvent is selected from the group consisting of polyethyleneglycols having a molecular weight between 400 and 1000, C2 to C 8 mono- and poly-alcohols, and C 7 to C 18 alcohols of linear or branched configuration.
6 . The composition of claim 5 , wherein the polar solvent comprises polyethylene glycol.
7 . The composition of claim 5 , wherein the polar solvent comprises ethanol.
8 . The composition of claim 2 , wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
9 . The composition of claim 1 , wherein the propellant is selected from the group consisting of propane, N-butane, iso-butane, N-pentane, iso-pentane, neo-pentane, and mixtures thereof.
10 . The composition of claim 1 , wherein the pharmaceutically acceptable ester of testosterone is selected from the group consisting of testosterone propionate, testosterone enanthate, and testosterone cypionate.
11 . A method of administering testosterone or a pharmaceutically acceptable ester thereof to a mammal, comprising spraying the oral mucosa of the mammal with the composition of claim 1 .
12 . The method of claim 11 , wherein the amount of the spray is predetermined.
13 - 29 . (canceled)
30 . An oral spray composition for transmucosal administration of testosterone or a pharmaceutically acceptable ester thereof comprising: testosterone or a pharmaceutically acceptable ester thereof in an amount between 0.05 and 50 percent by weight of the total composition; a mixture of a polar and a non-polar solvent in an amount between 10 and 97 percent by weight of the total composition, wherein the ratio of the polar solvent to the non-polar solvent ranges from 1:99 to 99:1; and a propellant in an amount between 5 and 80 percent by weight of the total composition, wherein said propellant is a C 3 to C 8 hydrocarbon of linear or branched configuration.
31 . The composition of claim 30 , further comprising a taste mask and/or flavoring agent is present in an amount between 0.01 and 10 percent by weight of the total composition.
32 . The composition of claim 31 , wherein the propellant is present in an amount between 10 and 70 percent by weight of the total composition, the solvent is present in an amount between 20 and 97 percent by weight of the total composition, the testosterone or a pharmaceutically acceptable ester thereof is present in an amount from between 0.1 and 40 percent by weight of the total composition, and the taste mask and/or flavoring agent is present in an amount between 1 and 8 percent by weight of the total composition.
33 . The composition of claim 30 , wherein the propellant is selected from the group consisting of propane, n-butane, iso-butane, n-pentane, iso-pentane, neo-pentane, and mixtures thereof.
34 . The composition of claim 33 , wherein the propellant is n-butane or iso-butane and has a water content of not more than 0.2 percent and a concentration of oxidizing agents, reducing agents, Lewis acids, and Lewis bases of less than 0.1 percent.
35 . The composition of claim 30 , wherein the polar solvent is selected from the group consisting of polyethylene glycols having a molecular weight between 400 and 1000, C 2 to C 8 mono- and poly-alcohols, and C 7 to C 1 s alcohols of linear or branched configuration and the non-polar solvent is selected from the group consisting of (C 2 -C 24 ) fatty acid (C 2 -C 6 ) esters, C 7 -C 18 hydrocarbons of linear or branched configuration, C 2 -C 6 alkanoyl esters, and triglycerides of C 2 -C 6 carboxylic acids.
36 . The composition of claim 30 , wherein the pharmaceutically acceptable ester of testosterone is selected from the group consisting of testosterone propionate, testosterone enanthate, and testosterone cypionate.
37 . A method of administering testosterone or a pharmaceutically acceptable ester thereof to a mammal, comprising spraying the oral mucosa of the mammal with the composition of claim 30 .
38 . The method of claim 37 , wherein the amount of the spray is predetermined.
39 . A method of treating hypogonadism in a patient by spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of claim 1 .
40 . A method of improving muscle development in a patient by spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of claim 1 .
41 . A method of stimulating erythropoiesis in a patient by spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of claim 1 .
42 . A method of treating anemia in a patient by spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of claim 1 .
43 . The method of claim 67 , wherein the anemia is associated with failure of bone marrow, myelofibrosis, or renal failure.
44 . A method of treating angioneurotic edema in a patient by spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of claim 1 .
45 . A method of treating growth retardation in a patient by spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of claim 1 .
46 . A method of treating carcinoma of the breast in a women by spraying the oral mucosa of the women with a therapeutically effective amount of the spray of claim 1 .
47 . A method of treating osteoporosis in a patient by spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of claim 1 .
48 - 65 . (canceled)
66 . A method of treating hypogonadism in a patient by spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of claim 30 .
67 . A method of improving muscle development in a patient by spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of claim 30 .
68 . A method of stimulating erythropoiesis in a patient by spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of claim 30 .
69 . A method of treating anemia in a patient by spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of claim 30 .
70 . The method of claim 69 , wherein the anemia is associated with failure of bone marrow, myelofibrosis, or renal failure.
71 . A method of treating angioneurotic edema in a patient by spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of claim 30 .
72 . A method of treating growth retardation in a patient by spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of claim 30 .
73 . A method of treating carcinoma of the breast in a women by spraying the oral mucosa of the women with a therapeutically effective amount of the spray of claim 30 .
74 . A method of treating osteoporosis in a patient by spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of claim 30.