Buccal, polar and non-polar spray containing zolipidem

Abstract

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

1 - 62 . (canceled) 
     
     
         63 . A method of administering zolpidem to a mammal to provide transmucosal absorption of a pharmacologically effective amount of zolpidem 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: zolpidem or a pharmaceutically acceptable salt thereof in an amount of between 0.5 and 55 percent by weight of the total composition; and a non-polar solvent in an amount between 30 and 99 percent by weight of the total composition; and   wherein said spraying the oral mucosa results in transmucosal absorption of a pharmacologically effective amount of zolpidem through the oral mucosa to the systemic circulatory system of said mammal.   
     
     
         64 . The method of  claim 63 , wherein the composition further comprises a taste mask and/or flavoring agent in an amount between 0.1 and 10 percent by weight of the total composition. 
     
     
         65 . The method of  claim 63 , wherein 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. 
     
     
         66 . The method of  claim 65 , wherein the polar solvent comprises a triglyceride. 
     
     
         67 . The method of  claim 64 , 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. 
     
     
         68 . The method of  claim 63 , wherein the amount of the spray is predetermined. 
     
     
         69 . A method of administering zolpidem to a mammal to provide transmucosal absorption of a pharmacologically effective amount of zolpidem 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: zolpidem 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 said spraying the oral mucosa results in transmucosal absorption of a pharmacologically effective amount of zolpidem through the oral mucosa to the systemic circulatory system of said mammal.   
     
     
         70 . The method of  claim 69 , 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. 
     
     
         71 . The method of  claim 70 , wherein the flavoring agent is selected from the group consisting of or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof. 
     
     
         72 . A method of administering zolpidem to a mammal to provide transmucosal absorption of a pharmacologically effective amount of zolpidem 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: zolpidem 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; and   wherein said spraying the oral mucosa results in transmucosal absorption of a pharmacologically effective amount of zolpidem through the oral mucosa to the systemic circulatory system of said mammal.   
     
     
         73 . The method of  claim 72 , 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 zolpidem 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. 
     
     
         74 . The method of  claim 72 , wherein the propellant is selected from the group consisting of propane, n-butane, iso-butane, n-pentane, iso-pentane, neo-pentane, and mixtures thereof. 
     
     
         75 . The method of  claim 72 , wherein the propellant is n-butane or iso-butane and has a water content 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. 
     
     
         76 . The method of  claim 72 , 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. 
     
     
         77 . The method of  claim 76 , wherein the solvent is a triglyceride. 
     
     
         78 . The method of  claim 72 , wherein the amount of the spray is predetermined. 
     
     
         79 . A method of administering zolpidem to a mammal to provide transmucosal absorption of a pharmacologically effective amount of zolpidem 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: zolpidem 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 said spraying the oral mucosa results in transmucosal absorption of a pharmacologically effective amount of zolpidem through the oral mucosa to the systemic circulatory system of said mammal.   
     
     
         80 . The method of  claim 79 , 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. 
     
     
         81 . The method of  claim 80 , 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 zolpidem 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. 
     
     
         82 . The method of  claim 79 , wherein the propellant is selected from the group consisting of propane, n-butane, iso-butane, n-pentane, iso-pentane, neo-pentane, and mixtures thereof. 
     
     
         83 . The method of  claim 82 , 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. 
     
     
         84 . The method of  claim 79 , 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. 
     
     
         85 . A method of administering zolpidem to a mammal to provide transmucosal absorption of a pharmacologically effective amount of zolpidem 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: zolpidem or a pharmaceutically acceptable salt thereof in an amount between 0.001 and 60 percent by weight of the total composition; and a mixture of a polar solvent and a non-polar solvent in an amount between 30 and 99.69 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   wherein said spraying the oral mucosa results in transmucosal absorption of a pharmacologically effective amount of zolpidem through the oral mucosa to the systemic circulatory system of said mammal.   
     
     
         86 . The method of  claim 85 , 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.