Buccal, polar and non-polar spray or capsule containing drugs for treating pain

Abstract

Buccal aerosol sprays or capsules using polar and non-polar solvent have now been developed which provide biologically active compounds 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, active compound, and optional flavoring agent; formulation II: aqueous polar solvent, active compound, optionally flavoring agent, and propellant; formulation III: non-polar solvent, active compound, and optional flavoring agent; and formulation IV: non-polar solvent, active compound, optional flavoring agent, and propellant.

1 - 76 . (canceled) 
   
   
       77 . A method of administering an effective amount of a pharmacologically active compound to a mammal to provide transmucosal absorption of a therapeutically effective amount of the active compound 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 propellant free buccal spray composition comprising:
 an active compound in an amount between 0.001 and 60 percent by weight of the total composition comprising an anti-opioid agent, an anti-migraine agent, an anesthetic, a pain control agent selected from the group consisting of alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol or a pharmaceutically acceptable salt thereof, or a mixture thereof; and   a polar solvent in an amount between 30 and 99.69 percent by weight of the total composition.   
   
   
       78 . The method of  claim 77 , further comprising a flavoring agent in an amount between 0.1 and 10 percent by weight of the total composition. 
   
   
       79 . The method of  claim 78 , wherein the polar solvent is present in an amount between 37 and 98.58 percent by weight of the total composition, the active compound is present in an amount between 0.005 and 55 percent by weight of the total composition, and the flavoring agent is present in an amount between 0.5 and 8 percent by weight of the total composition. 
   
   
       80 . The method of  claim 79 , wherein the polar solvent is present in an amount between 60.9 and 97.06 percent by weight of the total composition, the active compound is present in an amount between 0.01 and 40 percent by weight of the total composition, and the flavoring agent is present in an amount between 0.75 and 7.5 percent by weight of the total composition. 
   
   
       81 . The method of  claim 77 , wherein the polar solvent comprises a polyethylene glycol having a molecular weight between 400 and 1000, a C 2  to C 8  mono- and polyalcohol, or a C 7  to C 18  alcohol of linear or branched configuration. 
   
   
       82 . The method of  claim 77 , wherein the polar solvent comprises aqueous polyethylene glycol. 
   
   
       83 . The method of  claim 77 , wherein the polar solvent comprises aqueous ethanol. 
   
   
       84 . The method of  claim 77 , wherein the active compound is selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin or a pharmaceutically acceptable salt thereof. 
   
   
       85 . The method of  claim 77 , wherein the active compound is selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan or a pharmaceutically acceptable salt thereof. 
   
   
       86 . The method of  claim 77 , wherein the active compound is selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocalne, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine or a pharmaceutically acceptable salt thereof. 
   
   
       87 . The method of  claim 78 , wherein the flavoring agent comprises a synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavor, sweetener or a mixture thereof. 
   
   
       88 . The method of  claim 77 , wherein the amount of the spray is predetermined. 
   
   
       89 . A method of administering an effective amount of a pharmacologically active compound to a mammal to provide transmucosal absorption of a therapeutically effective amount of the active compound 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 propellant free buccal spray composition comprising:
 an active compound in an amount between 0.005 and 55 percent by weight of the total composition comprising an anti-opioid agent, an anti-migraine agent, a pain control agent, an anesthetic or a mixture thereof; and   a non-polar solvent in an amount between 30 and 99.69 percent by weight of the total composition.   
   
   
       90 . The method of  claim 89 , further comprising a flavoring agent in an amount between 0.1 and 10 percent by weight of the total composition. 
   
   
       91 . The method of  claim 89 , wherein the active compound is selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin or a pharmaceutically acceptable salt thereof. 
   
   
       92 . The method of  claim 89 , wherein the active compound is selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan or a pharmaceutically acceptable salt thereof. 
   
   
       93 . The method of  claim 89 , wherein the active compound is selected from the group consisting of a non-steroidal anti-inflammatory drug, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine sufentanil, tramadol or a pharmaceutically acceptable salt thereof. 
   
   
       94 . The method of  claim 89 , wherein the active compound is selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocalne, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine or a pharmaceutically acceptable salt thereof. 
   
   
       95 . The method of  claim 90 , wherein the flavoring agent comprises a synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavor, sweetener or a mixture thereof. 
   
   
       96 . The method of  claim 89 , wherein the solvent comprises a (C 2 -C 24 ) fatty acid (C 2 -C 6 ) ester, a C 7 -C 18  hydrocarbon of linear or branched configuration, a C 2 -C 6  alkanoyl ester, or a triglyceride of C 2 -C 6  carboxylic acid. 
   
   
       97 . The method of  claim 96 , wherein the solvent comprises one or more fatty acid esters. 
   
   
       98 . The method of  claim 89 , wherein the amount of the spray is predetermined. 
   
   
       99 . A method for administering an effective amount of a pharmacologically active compound to a mammal to provide transmucosal absorption of a therapeutically effective amount of the active compound 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 propellant free buccal spray composition, containing a pharmacologically active compound dissolved in a pharmacologically acceptable solvent, comprising in weight percent of the composition:   an active compound in an amount between 0.001 and 60 percent by weight of the total composition comprising an anti-opioid agent, an anti-migraine agent, a pain control agent, an anesthetic or a mixture thereof; and   a polar solvent in an amount between 30 and 99.69 percent by weight of the total composition.   
   
   
       100 . The method of  claim 99 , further comprising a flavoring agent in an amount between 0.1 and 10 percent by weight of the total composition. 
   
   
       101 . The method of  claim 100 , wherein the polar solvent is present in an amount between 37 and 98.58 percent by weight of the total composition, the active compound is present in an amount between 0.005 and 55 percent by weight of the total composition, and the flavoring agent is present in an amount between 0.5 and 8 percent by weight of the total composition. 
   
   
       102 . The method of  claim 101 , wherein the polar solvent is present in an amount between 60.9 and 97.06 percent by weight of the total composition, the active compound is present in an amount between 0.01 and 40 percent by weight of the total composition, and the flavoring agent is present in an amount between 0.75 and 7.5 percent by weight of the total composition. 
   
   
       103 . The method of  claim 99 , wherein the polar solvent comprises a polyethylene glycol having a molecular weight between 400 and 1000, a C 2  to C 8  mono- and polyalcohol, or a C 7  to C 18  alcohol of linear or branched configuration. 
   
   
       104 . The method of  claim 99 , wherein the polar solvent comprises aqueous polyethylene glycol. 
   
   
       105 . The method of  claim 99 , wherein the polar solvent comprises aqueous ethanol. 
   
   
       106 . The method of  claim 99 , wherein the active compound is selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin or a pharmaceutically acceptable salt thereof. 
   
   
       107 . The method of  claim 99 , wherein the active compound is selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan or a pharmaceutically acceptable salt thereof. 
   
   
       108 . The method of  claim 99 , wherein the active compound is selected from the group consisting of a non-steroidal anti-inflammatory drug, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol or a pharmaceutically acceptable salt thereof. 
   
   
       109 . The method of  claim 99 , wherein the active compound is selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocalne, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine or a pharmaceutically acceptable salt thereof. 
   
   
       110 . The method of  claim 99 , wherein the flavoring agent comprises a synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavor, sweetener or a mixture thereof. 
   
   
       111 . A method for administering an effective amount of a pharmacologically active compound to a mammal to provide transmucosal absorption of a therapeutically effective amount of the active compound 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 propellant free buccal spray composition, containing a pharmacologically active compound dissolved in a pharmacologically acceptable solvent, comprising in weight percent of the composition:   an active compound in an amount between 0.005 and 55 percent by weight of the total composition comprising an anti-opioid agent, an anti-migraine agent, a pain control agent, an anesthetic or a mixture thereof; and   a non-polar solvent in an amount between 30 and 99.69 percent by weight of the total composition.   
   
   
       112 . The method of  claim 111 , further comprising a flavoring agent in an amount between 0.1 and 10 percent by weight of the total composition. 
   
   
       113 . The method of  claim 111 , wherein the active compound is selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin or a pharmaceutically acceptable salt thereof. 
   
   
       114 . The method of  claim 111 , wherein the active compound is selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan or a pharmaceutically acceptable salt thereof. 
   
   
       115 . The method of  claim 111 , wherein the active compound is selected from the group consisting of a non-steroidal anti-inflammatory drug, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine sufentanil, tramadol or a pharmaceutically acceptable salt thereof. 
   
   
       116 . The method of  claim 111 , wherein the active compound is selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocalne, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine or a pharmaceutically acceptable salt thereof. 
   
   
       117 . The method of  claim 112 , wherein the flavoring agent comprises a synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavor, sweetener or a mixture thereof. 
   
   
       118 . The method of  claim 111 , wherein the solvent comprises a (C 2 -C 24 ) fatty acid (C 2 -C 6 ) ester, a C 7 -C 18  hydrocarbon of linear or branched configuration, a C 2 -C 6  alkanoyl ester, or a triglyceride of C 2 -C 6  carboxylic acid. 
   
   
       119 . The method of  claim 118 , wherein the solvent comprises one or more fatty acid esters. 
   
   
       120 . A method of administering an anti-migraine effective amount of sumatriptan to a mammal to provide transmucosal absorption of a therapeutically effective amount of sumatriptan 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 propellant free buccal spray composition comprising:
 sumatriptan or a pharmaceutically acceptable salt thereof in an amount between 1 and 20 percent by weight of the total composition; and   a polar solvent in an amount between 5 and 60 percent by weight of the total composition, wherein said polar solvent is selected from the group consisting of water, propylene glycol, polyethylene glycol, and mixtures thereof.