Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system

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 - 134 . (canceled) 
     
     
         135 . 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 acetylcholinesterase inhibitor, a nerve impulse inhibitor, an anti-cholinergic, an anti-convulsant, an anti-psychotic, an anxiolytic agent, a dopamine metabolism inhibitor, an agent for treating post stroke sequelae, a neuroprotectant, an agent treating Alzheimer's disease, a neurotransmitter, a neurotransmitter agonist, a sedative, an agent for treating attention deficit disorder, an agent for treating narcolepsy, a central adregenic antagonist, an anti-depression agent, an agent for treating Parkinson's disease, a benzodiazepine antagonist, a stimulant, a neurotransmitter antagonist, a tranquilizer or a mixture thereof; and   a polar solvent in an amount between 30 and 99.69 percent by weight of the total composition.   
     
     
         136 . The method of  claim 135 , wherein the active compound is an acetylcholinesterase inhibitor comprising galantamine, neostigmine, physostigmine, edrophonium or a mixture thereof. 
     
     
         137 . The method of  claim 135 , wherein the active compound is a nerve impulse inhibitor comprising levobupivacaine, lidocaine, prilocaine, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxaurium, mivacuium, pancuronium, vercuronium, pipecuronium, rocurronium or a mixture thereof. 
     
     
         138 . The method of  claim 135 , wherein the active compound is an anti-cholinergic comprising amantadine, ipratropium, oxitropium, dicycloverine or a mixture thereof. 
     
     
         139 . The method of  claim 135 , wherein the active compound is an anti-convulsant comprising acetazolamide, carbamazepine, clonazepam, diazepam, divalproex, ethosuximide, lamotrignine acid, levetriacetam, oxcarbazepine, Phenobarbital, phenyloin, pregabalin, primidone, remacemide, trimethadione, topiramate, vigabatrin, zonisamide or a mixture thereof. 
     
     
         140 . The method of  claim 135 , wherein the active compound is an anti-psychotic comprising amisulpride, aripiprazole bifemelane, bromperidol, clozapine, chlorpromazine, haloperidol, iloperidone loperidone, olanzapine, quetiapine, fluphenazine, esperidone, thiothixene, thioridazine, sulpride, ziprasidone or a mixture thereof. 
     
     
         141 . The method of  claim 135 , wherein the active compound is an anxiolytic agent comprising amitryptiline, atracurium, buspirone, chlorzoxazone, clorazepate, cisatracurium, cyclobenzaprine, eperisone, esopiclone, hydroxyzine, mirtazapine, mivacurium, pagoclone, superide, zaleplon, zopiclone or a mixture thereof. 
     
     
         142 . The method of  claim 135 , wherein the active compound is a dopamine metabolism inhibitor comprising entacapone, lazebemide, selegiline, tolcapone or a mixture thereof. 
     
     
         143 . The method of  claim 135 , wherein the active compound is an agent for treating post stroke sequelae comprising glatiramer, estradiol, progesterone or a mixture thereof. 
     
     
         144 . The method of  claim 135 , wherein the active compound is a neuroprotectant comprising donepezil, memanine, nimodipine, riluzole, rivastigmine, tacrine, xaliproden or a mixture thereof. 
     
     
         145 . The method of  claim 135 , wherein the active compound is a agent for treating Alzheimer's disease comprising carbidopa, levodopa, tacrine, donezepil, rivastigmine, galantamine or a mixture thereof. 
     
     
         146 . The method of  claim 135 , wherein the active compound is a neurotransmitter comprising acetylcholine, serotonin, 5-hydroxytryptamine (5-HT), GABA, glutamate, aspartate, glycine, histamine, epinephrine, norpinephrine, dopamine, adenosine, ATP nitric oxide or a mixture thereof. 
     
     
         147 . The method of  claim 135 , wherein the active compound is a neurotransmitter agonist comprising almotriptan, aniracetam, atomoxetine, benserazide, bromocriptine, bupropion, cabergoline, citalopram, clomipramine, desipramine, diazepam, dihydroergotmine, doxepin duloxetine, eletriptan, escitalopram, fluvoxamine, gabapentin, imipramine, moclobemide, naratriptan, nefazodone, nefiracetam acamprosate, nicergoline, nortryptiline, paroxetine, pergolide, pramipexole, rizatriptan, ropinirole, sertraline, sibutramine, sumatriptan, tiagabine, trazodone, venlafaxine, zolmitriptan or a mixture thereof. 
     
     
         148 . The method of  claim 135 , wherein the active compound is a sedative comprising dexmedetomidine, eszopiclone, indiplon, zolpidem, zaleplon or a mixture thereof. 
     
     
         149 . The method of  claim 135 , wherein the active compound is an agent for treating attention deficit disorder comprising amphetamine, dextroamphetamine, methylphenidate, pemoline or a mixture thereof. 
     
     
         150 . The method of  claim 135 , wherein the active compound is an agent for treating narcolepsy comprising modafinil, mazindol or a mixture thereof. 
     
     
         151 . The method of  claim 135 , wherein the active compound is an anti-depression agent comprising amitriptyline, amoxapine, bupropion, clomipramine, clorgyline, despipramine, doxepin, fluoxetine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline, sertraline, tranylcypromine, trazodone, venlafaxine or a mixture thereof. 
     
     
         152 . The method of  claim 135 , wherein the active compound is an agent for treating Parkinson's disease comprising amantadine, bromocriptine, carvidopa, levodopa, pergolide, selegiline or a mixture thereof. 
     
     
         153 . The method of  claim 135 , wherein the active compound comprises flumazenil. 
     
     
         154 . The method of  claim 135 , wherein the active compound comprises deramciclane. 
     
     
         155 . The method of  claim 135 , wherein the active compound is a stimulant comprising amphetamine, dextroamphetamine, dinoprostone, methylphenidate, methylphenidate, modafinil, pemoline or a mixture thereof. 
     
     
         156 . The method of  claim 135 , wherein the active compound comprises mesoridazine. 
     
     
         157 . The method of  claim 135 , wherein the amount of the spray is predetermined. 
     
     
         158 . The method of  claim 135 , further comprising a flavoring agent in an amount between 0.1 and 10 percent by weight of the total composition. 
     
     
         159 . The method of  claim 158 , wherein the flavoring agent comprises a synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavor, sweetener or a mixture thereof. 
     
     
         160 . The method of  claim 158 , 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. 
     
     
         161 . The method of  claim 160 , wherein the polar solvent is present in an amount between 60.9 and 97.06 percent by eight 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. 
     
     
         162 . The method of  claim 135 , 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. 
     
     
         163 . The method of  claim 135 , wherein the polar solvent comprises aqueous polyethylene glycol. 
     
     
         164 . The method of  claim 135 , wherein the polar solvent comprises aqueous ethanol. 
     
     
         165 . 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 acetylcholinesterase inhibitor, a nerve impulse inhibitor, an anti-cholinergic, an anti-convulsant, an anti-psychotic, an anxiolytic agent, a dopamine metabolism inhibitor, an agent for treating post stroke sequelae, a neuroprotectant, an agent treating Alzheimer's disease, a neurotransmitter, a neurotransmitter agonist, a sedative, an agent for treating attention deficit disorder, an agent for treating narcolepsy, a central adregenic antagonist, an anti-depression agent, an agent for treating Parkinson's disease, a benzodiazepine antagonist, a stimulant, a neurotransmitter antagonist, a tranquilizer or a mixture thereof; and   a non-polar solvent in an amount between 30 and 99.69 percent by weight of the total composition.   
     
     
         166 . The method of  claim 165 , further comprising a flavoring agent in an amount between 0.1 and 10 percent by weight of the total composition. 
     
     
         167 . The method of  claim 165 , wherein the active compound is an acetylcholinesterase inhibitor comprising galantamine, neostigmine, physostigmine, and edrophonium or a mixture thereof. 
     
     
         168 . The method of  claim 165 , wherein the active compound is a nerve impulse inhibitor comprising levobapivacaine, lidocaine, prilocaine, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxaurium, mivacuium, pancuronium, vercuronium, pipecuronium, rocuronium or a mixture thereof. 
     
     
         169 . The method of  claim 165 , wherein the active compound is an anti-cholinergic comprising amantadine, ipretropium, oxitropium, dicycloverine or a mixture thereof. 
     
     
         170 . The method of  claim 165 , wherein the active compound is an anti-convulsant comprising acetazloamide, earbamazepine, clonazepatn, diazepam, divalproex, ethosuximide, lamotrignine acid, levetriacetam, oxcarbazepine, phenobarbital, phenyloin, pregabalin, primidone, remacemide, trimethadione, topiramate, vigabatrin, zonisamide or a mixture thereof. 
     
     
         171 . The method of  claim 165 , wherein the active compound is an anti-psychotic comprising amisulpride, aripiprazole bifemelane, bromperidol, clozapine, chlorpromazine, haloperidol, iloperidone loperidone, olanzapine, quetiapine, fluphenazine, risperidone, thiothixene, thioridazine, sulpride, ziprasidone or a mixture thereof. 
     
     
         172 . The method of  claim 165 , wherein the active compound is an anxiolytic agent comprising amitryptiline, atracurium, buspirone, chlorzoxazone, clorazepate, cisatracurium, cyclobenzaprine, eperisone, esopiclone, hydroxyzine, mirtazapine, mivacurium, pagoclone, sulperide, zaleplon, zopiclone or a mixture thereof. 
     
     
         173 . The method of  claim 165 , wherein the active compound is a dopamine metabolism inhibitor comprising entacapone, lazebemide, selegiline, tolcapone or a mixture thereof. 
     
     
         174 . The method of  claim 165 , wherein the active compound is an agent for treating post stroke sequelae comprising glatiramer, estradiol, progesterone or a mixture thereof. 
     
     
         175 . The method of  claim 165 , wherein the active compound is a neuroprotectant comprising donepezil, memanine, nimodipine, riluzole, rivastigmine, tacrine, xaliproden or a mixture thereof. 
     
     
         176 . The method of  claim 165 , wherein the active compound is an agent for treating Alzheimer's disease comprising carbidopa, lelvodopa, tacrine, donezepil, rivastigmine, galantamine or a mixture thereof. 
     
     
         177 . The method of  claim 165 , wherein the active compound is a neurotransmitter comprising acetylcholine, serotonin, 5-hydroxytryptamine (5-HT), GABA, glutamate, aspartate, glycine, histamine, epinephrine, norpinephrine, dopamine, adenosine, ATP, nitric oxide or a mixture thereof. 
     
     
         178 . The method of  claim 165 , wherein the active compound is a neurotransmitter agonist comprising almotriptan, aniracetam, atomoxetine, benserazide, bromociptine, bupropion, cabergoline, citalopram, clomipramine, desipramine, diazepam, dihydroergotamine, doxepin duloxetine, eletriptan, escitalopram, fluvoxamine, gabapentin, imipramine, moclobemide, naratriptan, nefazodone, nefiracetam, acamprosate, nicergoline, nortryptiline, paroxetine, pergolide, pramipexole, rizatriptan, ropinirole, sertraline, sibutramine, sumatriptan, tiagabine, trazodone, venlafaxine, zolmitriptan or a mixture thereof. 
     
     
         179 . The method of  claim 165 , wherein the active compound is a sedative comprising dexmedetomidine, eszopiclone, indiplon, zolpidem, zaleplon or a mixture thereof. 
     
     
         180 . The method of  claim 165 , wherein the active compound is an agent for treating attention deficit disorder comprising amphetamine, dextroamphetamine, methylphenidate, pemoline or a mixture thereof. 
     
     
         181 . The method of  claim 165 , wherein the active compound is an agent for treating narcolepsy comprising modafinil, mazindol or a mixture thereof. 
     
     
         182 . The method of  claim 165 , wherein the active compound is an anti-depression agent comprising amitriptyline, amoxapine, bupropion, clomipramine, clomipramine, clorgyline, despipramine, doxepin, fluoxetine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline, sentraline, tranylcyporomine, trazodone, venlafaxine or a mixture thereof. 
     
     
         183 . The method of  claim 165 , wherein the active compound is an agent for treating Parkinson's disease comprising amantadine, bromocriptine, carvidopa, levodopa, pergolide, selegiline or a mixture thereof. 
     
     
         184 . The method of  claim 165 , wherein the active compound comprises flumazenil. 
     
     
         185 . The method of  claim 165 , wherein the active compound comprises deramciclane. 
     
     
         186 . The method of  claim 165 , wherein the active compound is a stimulant comprising amphetamine, dextroamphetamine, dinoprostone, methylphenidate, methylphenidate, modafinil, pemoline or a mixture thereof. 
     
     
         187 . The method of  claim 165 , wherein the active compound comprises mesoridazine. 
     
     
         188 . The method of  claim 165 , wherein the amount of the spray is predetermined. 
     
     
         189 . The method of  claim 165 , further comprising a flavoring agent which comprises a synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavor, sweetener or a mixture thereof. 
     
     
         190 . The method of  claim 165 , 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. 
     
     
         191 . The method of  claim 190 , wherein the solvent comprises one or more fatty acid esters. 
     
     
         192 . A method for administering an effective amount of a pharmacologically active sedative to a mammal to provide transmucosal absorption of a therapeutically effective amount of the sedative 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 sedative dissolved in a pharmacologically acceptable solvent, comprising in weight percent of the composition:   zolpidem in an amount between 0.001 and 60 percent by weight of the total composition; and   propylene glycol in an amount between 30 and 99.69 percent by weight of the total composition;   wherein a therapeutically effective amount of zolpidem is absorbed through the oral mucosa to the systemic circulatory system to the mammal.