Buccal, polar and non-polar spray containing ondansetron

Abstract

Buccal aerosol sprays or capsules using polar and non-polar solvents have now been developed which provide ondansetron 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, ondansetron, and optional flavoring agent; formulation II: aqueous polar solvent, ondansetron, optionally flavoring agent, and propellant; formulation III: non-polar solvent, ondansetron, and optional flavoring agent; formulation IV: non-polar solvent, ondansetron, optional flavoring agent, and propellant; formulation V: a mixture of a polar solvent and a non-polar solvent, ondansetron, and optional flavoring agent; formulation VI: a mixture of a polar solvent and a non-polar solvent, ondansetron, optional flavoring agent, and propellant.

1 - 10 . (canceled)  
     
     
         11 . An oral spray composition for transmucosal administration of ondansetron or a pharmaceutically acceptable salt thereof comprising: ondansetron or a pharmaceutically acceptable salt 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.  
     
     
         12 . The composition of  claim 11 , further comprising a taste mask and/or flavoring agent in an amount between 0.05 and 10 percent by weight of the total composition.  
     
     
         13 . The composition of  claim 12 , wherein the polar solvent is present in an amount between 20 and 97 percent by weight of the total composition, the ondansetron or a pharmaceutically acceptable salt 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.  
     
     
         14 . The composition of  claim 13 , wherein the polar solvent is present in an amount between 25 and 97 percent by weight of the total composition, the ondansetron or a pharmaceutically acceptable salt 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.  
     
     
         15 . The composition of  claim 11 , wherein the polar solvent is selected from the group consisting of polyethyleneglycols having a molecular weight between 400 and 1000, C 2  to C 8  mono- and poly-alcohols, and C 7  to C 18  alcohols of linear or branched configuration.  
     
     
         16 . The composition of  claim 15 , wherein the polar solvent comprises polyethylene glycol.  
     
     
         17 . The composition of  claim 15 , wherein the polar solvent comprises ethanol.  
     
     
         18 . The composition of  claim 12 , 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.  
     
     
         19 . The composition of  claim 11 , wherein the propellant is selected from the group consisting of propane, N-butane, iso-butane, N-pentane, iso-pentane, neo-pentane, and mixtures thereof.  
     
     
         20 . A method of administering ondansetron or a pharmaceutically acceptable salt thereof to a mammal, comprising spraying the oral mucosa of the mammal with the composition of  claim 11 .  
     
     
         21 . The method of  claim 20 , wherein the amount of the spray is predetermined.  
     
     
         22 - 28 . (canceled)  
     
     
         29 . An oral spray composition for transmucosal administration of ondansetron or a pharmaceutically acceptable salt thereof comprising: ondansetron or a pharmaceutically acceptable salt thereof in an amount between 0.05 and 50 percent by weight of the total composition; and a non-polar solvent in an amount between 19 and 85 percent by weight of the total composition; 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.  
     
     
         30 . The composition of  claim 29 , further comprising a taste mask and/or flavoring agent in an amount of between 0.1 and 10 percent by weight of the total composition.  
     
     
         31 . The composition of  claim 30 , 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.  
     
     
         32 . An oral spray composition for transmucosal administration of ondansetron or a pharmaceutically acceptable salt thereof comprising: ondansetron or a pharmaceutically acceptable salt thereof in an amount between 0.01 and 40 percent by weight of the total composition; a non-polar solvent in an amount between 25 and 89 percent by weight of the total composition; a propellant in an amount between 10 and 70 percent by weight of the total composition, wherein said propellant is a C 3  to C 8  hydrocarbon of linear or branched configuration; and a 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 32 , wherein the propellant is present in an amount between 20 and 70 percent by weight of the total composition, the non-polar solvent is present in an amount between 25 and 75 percent by weight of the total composition, the ondansetron or a pharmaceutically acceptable salt thereof is present in an amount from between 0.25 and 35 percent by weight of the total composition, and the taste mask and/or flavoring agent is present in an amount between 2 and 7.5 percent by weight of the total composition.  
     
     
         34 . The composition of  claim 29 , wherein the propellant is selected from the group consisting of propane, n-butane, iso-butane, n-pentane, iso-pentane, neo-pentane, and mixtures thereof.  
     
     
         35 . The composition of  claim 34 , 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.  
     
     
         36 . The composition of  claim 29 , wherein the 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.  
     
     
         37 . The composition of  claim 36 , wherein the solvent is a triglyceride.  
     
     
         38 . A method of administering ondansetron or a pharmaceutically acceptable salt thereof to a mammal, comprising spraying the oral mucosa of the mammal with the composition of  claim 29 .  
     
     
         39 . The method of  claim 38 , wherein the amount of the spray is predetermined.  
     
     
         40 - 48 . (canceled)  
     
     
         49 . An oral spray composition for transmucosal administration of ondansetron or a pharmaceutically acceptable salt thereof comprising: ondansetron or a pharmaceutically acceptable salt thereof in an amount between 0.05 and 50 percent by weight of the total composition; a mixture of a polar solvent 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.  
     
     
         50 . The composition of  claim 49 , 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.  
     
     
         51 . The composition of  claim 50 , 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 ondansetron or a pharmaceutically acceptable salt 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.  
     
     
         52 . The composition of  claim 49 , wherein the propellant is selected from the group consisting of propane, n-butane, iso-butane, n-pentane, iso-pentane, neo-pentane, and mixtures thereof.  
     
     
         53 . The composition of  claim 52 , 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.  
     
     
         54 . The composition of  claim 49 , 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 18  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.  
     
     
         55 . A method of administering ondansetron or a pharmaceutically acceptable salt thereof to a mammal, comprising spraying the oral mucosa of the mammal with the composition of  claim 49 .  
     
     
         56 . The method of  claim 55 , wherein the amount of the spray is predetermined.  
     
     
         57 - 64 . (canceled)  
     
     
         65 . A method of treating emesis in a patient, comprising spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of  claim 11 .  
     
     
         66 . The method of  claim 65 , wherein the emesis is caused by chemotherapy or radiation.  
     
     
         67 . The method of  claim 66 , further comprising administering to the patient a corticosteroid.  
     
     
         68 . The method of  claim 66 , further comprising administering to the patient dexamethasone.  
     
     
         69 . The method of  claim 66 , wherein the oral mucosa of the patient is sprayed between about 5 minutes and 2 hours before chemotherapy or radiation therapy begins.  
     
     
         70 . The method of  claim 69 , further comprising spraying the oral mucosa of the patient between about 1 hour and 6 hours after chemotherapy or radiation therapy ends.  
     
     
         71 . A method of administering anesthesia to a patient comprising spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of  claim 11  before the anesthesia is administered.  
     
     
         72 . A method of treating anxiety in a patient, comprising spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of  claim 11 .  
     
     
         73 - 80 . (canceled)  
     
     
         81 . A method of treating emesis in a patient, comprising spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of  claim 29 .  
     
     
         82 . The method of  claim 81 , wherein the emesis is caused by chemotherapy or radiation.  
     
     
         83 . The method of  claim 82 , further comprising administering to the patient a corticosteroid.  
     
     
         84 . The method of  claim 82 , further comprising administering to the patient dexamethasone.  
     
     
         85 . The method of  claim 82 , wherein the oral mucosa of the patient is sprayed between about 5 minutes and 2 hours before chemotherapy or radiation therapy begins.  
     
     
         86 . The method of  claim 85 , further comprising spraying the oral mucosa of the patient between about 1 hour and 6 hours after chemotherapy or radiation therapy ends.  
     
     
         87 . A method of administering anesthesia to a patient comprising spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of  claim 29  before the anesthesia is administered.  
     
     
         88 . A method of treating anxiety in a patient, comprising spraying the oral mucosa of the patient with a therapeutically effective amount of the buccal spray of  claim 29 .  
     
     
         89 - 96 . (canceled)  
     
     
         97 . A method of treating emesis in a patient, comprising spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of  claim 49 .  
     
     
         98 . The method of  claim 97 , wherein the emesis is caused by chemotherapy or radiation.  
     
     
         99 . The method of  claim 98 , further comprising administering to the patient a corticosteroid.  
     
     
         100 . The method of  claim 98 , further comprising administering to the patient dexamethasone.  
     
     
         101 . The method of  claim 98 , wherein the oral mucosa of the patient is sprayed between about 5 minutes and 2 hours before chemotherapy or radiation therapy begins.  
     
     
         102 . The method of  claim 101 , further comprising spraying the oral mucosa of the patient between about 1 hour and 6 hours after chemotherapy or radiation therapy ends.  
     
     
         103 . A method of administering anesthesia to a patient comprising spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of  claim 49  before the anesthesia is administered.  
     
     
         104 . A method of treating anxiety in a patient, comprising spraying the oral mucosa of the patient with a therapeutically effective amount of the spray of  claim 49.