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 - 104 . (canceled) 
   
   
       105 . A method of administering ondansetron to a mammal to provide transmucosal absorption of a therapeutically effective amount of ondansetron through the oral mucosa of the mammal to the systemic circulatory system of the mammal, comprising:
 spraying the oral mucosa of the mammal with a buccal spray composition comprising in weight percent of the composition: 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; and   wherein said spraying the oral mucosa results in transmucosal absorption of a therapeutically effective amount of ondansetron through the oral mucosa of said mammal.   
   
   
       106 . The method of  claim 105 , wherein the composition further comprises a taste mask and/or flavoring agent in an amount between 0.05 and 10 percent by weight of the total composition. 
   
   
       107 . The method of  claim 106 , 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. 
   
   
       108 . The method of  claim 107 , 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. 
   
   
       109 . The method of  claim 105 , 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. 
   
   
       110 . The method of  claim 109 , wherein the polar solvent comprises polyethylene glycol. 
   
   
       111 . The method of  claim 109 , wherein the polar solvent comprises ethanol. 
   
   
       112 . The method of  claim 106 , 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. 
   
   
       113 . The method of  claim 105 , wherein the propellant is selected from the group consisting of propane, N-butane, iso-butane, N-pentane, iso-pentane, neo-pentane, and mixtures thereof. 
   
   
       114 . The method of  claim 105 , wherein the amount of the spray is predetermined. 
   
   
       115 . A method of administering ondansetron to a mammal to provide transmucosal absorption of a therapeutically effective amount of ondansetron through the oral mucosa of the mammal to the systemic circulatory system of the mammal, comprising:
 spraying the oral mucosa of the mammal with a buccal spray composition comprising in weight percent of the composition: 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; and   wherein spraying the oral mucosa results in transmucosal absorption of a therapeutically effective amount of ondansetron through the oral mucosa of said mammal.   
   
   
       116 . The method of  claim 115 , wherein the composition further comprises a taste mask and/or flavoring agent in an amount of between 0.1 and 10 percent by weight of the total composition. 
   
   
       117 . The method of  claim 116 , 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. 
   
   
       118 . A method of administering ondansetron to a mammal to provide transmucosal absorption of a therapeutically effective amount of ondansetron through the oral mucosa of the mammal to the systemic circulatory system of the mammal, comprising:
 spraying the oral mucosa of the mammal with a buccal spray composition comprising in weight percent of the composition: 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 89.9 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; and   wherein spraying the oral mucosa results in transmucosal absorption of a therapeutically effective amount of ondansetron through the oral mucosa of said mammal.   
   
   
       119 . The method of  claim 118 , 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 74.75 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. 
   
   
       120 . The method of  claim 115 , wherein the propellant is selected from the group consisting of propane, n-butane, iso-butane, n-pentane, iso-pentane, neo-pentane, and mixtures thereof. 
   
   
       121 . The method of  claim 120 , 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. 
   
   
       122 . The method of  claim 115 , 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. 
   
   
       123 . The method of  claim 122 , wherein the solvent is a triglyceride. 
   
   
       124 . The method of  claim 115 , wherein the amount of the spray is predetermined. 
   
   
       125 . A method of administering ondansetron to a mammal to provide transmucosal absorption of a therapeutically effective amount of ondansetron through the oral mucosa of the mammal to the systemic circulatory system of the mammal, comprising:
 spraying the oral mucosa of the mammal with a buccal spray composition comprising in weight percent of the composition: 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; and   wherein spraying the oral mucosa results in transmucosal absorption of a therapeutically effective amount of ondansetron through the oral mucosa of said mammal.   
   
   
       126 . The method of  claim 125 , wherein the composition further comprises a taste mask and/or flavoring agent is present in an amount between 0.01 and 10 percent by weight of the total composition. 
   
   
       127 . The method of  claim 126 , 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. 
   
   
       128 . The method of  claim 125 , wherein the propellant is selected from the group consisting of propane, n-butane, iso-butane, n-pentane, iso-pentane, neo-pentane, and mixtures thereof. 
   
   
       129 . The method of  claim 128 , 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. 
   
   
       130 . The method of  claim 125 , 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. 
   
   
       131 . The method of  claim 125 , wherein the amount of the spray is predetermined. 
   
   
       132 . The method of  claim 105 , further comprising administering to the patient a corticosteroid. 
   
   
       133 . The method of  claim 105 , further comprising administering to the patient dexamethasone. 
   
   
       134 . The method of  claim 105 , wherein the oral mucosa of the patient is sprayed between about 5 minutes and 2 hours before chemotherapy or radiation therapy begins. 
   
   
       135 . The method of  claim 134 , further comprising spraying the oral mucosa of the patient between about 1 hour and 6 hours after chemotherapy or radiation therapy ends. 
   
   
       136 . The method of  claim 115 , further comprising administering to the patient a corticosteroid. 
   
   
       137 . The method of  claim 115 , further comprising administering to the patient dexamethasone. 
   
   
       138 . The method of  claim 115 , wherein the oral mucosa of the patient is sprayed between about 5 minutes and 2 hours before chemotherapy or radiation therapy begins. 
   
   
       139 . The method of  claim 138 , further comprising spraying the oral mucosa of the patient between about 1 hour and 6 hours after chemotherapy or radiation therapy ends. 
   
   
       140 . The method of  claim 125 , further comprising administering to the patient a corticosteroid. 
   
   
       141 . The method of  claim 125 , further comprising administering to the patient dexamethasone. 
   
   
       142 . The method of  claim 125 , wherein the oral mucosa of the patient is sprayed between about 5 minutes and 2 hours before chemotherapy or radiation therapy begins. 
   
   
       143 . The method of  claim 142 , further comprising spraying the oral mucosa of the patient between about 1 hour and 6 hours after chemotherapy or radiation therapy ends. 
   
   
       144 . A method of treating chemotherapy or radiation induced nausea and/or vomiting in a mammal, comprising:
 spraying the oral mucosa of the mammal with a buccal spray composition comprising in weight percent of the composition: 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; and   wherein said spraying the oral mucosa occurs between about 1 hour and 6 hours after administration of chemotherapy or radiation therapy and results in transmucosal absorption of a therapeutically effective amount of ondansetron through the oral mucosa of said mammal to prevent chemotherapy or radiation induced nausea and/or vomiting.