Details for Patent: 9,308,208

Title:	Aerosol generating method and device
Abstract:	A method and device are provided to generate an aerosol having a desired particle sizes, i.e., from molecular to about 10 microns, which can be used to effectively deliver a physiologically active compound to organs and tissues such as the lung, eye, mucosa and skin. The aerosol is formed through vaporization of the compound while mixing the resulting vapor with a gas, in a ratio, to form the desired particle size when a stable concentration of particles in the gas is reached.
Inventor(s):	Wensley; Martin J. (Los Gatos, CA), Mufson; Daniel (Napa, CA), Hodges; Craig C. (Walnut Creek, CA), Lloyd; Peter M. (Walnut Creek, CA), Rogers; Daniel D. (Oakland, CA)
Assignee:	ALEXZA PHARMACEUTICALS, INC. (Mountain View, CA)
Filing Date:	Jul 30, 2010
Application Number:	12/847,584
Claims:	1. A method for generating an aerosol comprising the steps of: (a) depositing a coating comprising a physiologically active compound onto a substrate comprising dissolving the compound in an organic solvent, applying the solution to all or a portion of the substrate and allowing the solvent to evaporate; (b) heating the physiologically active compound to vaporize at least a portion of the compound, following said evaporation; (c) cooling the resulting vapor by mixing the vapor with a gas in a predetermined ratio, selected to form an aerosol comprised of particles within a desired size range when a stable concentration of particles in the gas is reached. 2. The method of claim 1 wherein the desired size range is a mass median aerodynamic diameter between about 1 to 3 microns. 3. The method of claim 1 wherein the desired size range is a mass median aerodynamic diameter between about 10 to 100 nanometers. 4. The method of claim 1 wherein the gas is air. 5. The method of claim 1 wherein the compound is selected from the group consisting of cannabinoid extracts from cannabis, THC, ketorolac, fentanyl, morphine, testosterone, ibuprofen, codeine, nicotine, Vitamin A, Vitamin E acetate, Vitamin E, nitroglycerin, pilocarpine, mescaline, testosterone enanthate, menthol, phencaramide, methsuximide, eptastigmine, promethazine, procaine, retinol, lidocaine, trimeprazine, isosorbide dinitrate, timolol, methyprylon, etamiphyllin, propoxyphene, salmetrol, vitamin E succinate, methadone, oxprenolol, isoproterenol bitartrate, etaqualone, Vitamin D3, ethambutol, ritodrine, omoconazole, cocaine, lomustine, ketamine, ketoprofen, cilazaprol, propranolol, sufentanil, metaproterenol, pentoxapylline, captopril, loxapine, cyproheptidine, carvediol, trihexylphenadine, alprostadil, melatonin, testosterone proprionate, valproic acid, acebutolol, terbutaline, diazepam, topiramate, pentobarbital, alfentanil HCl, papaverine, nicergoline, fluconazole, zafirlukast, testosterone acetate, droperidol, atenolol, metoclopramide, enalapril, albuterol, ketotifen, isoproterenol, amidarone HCl, zileuton, midazolam, oxycodone, cilostazol, propofol, nabilone, gabapentin, famotidine, lorezepam, naltrexone, acetaminophen, sumatriptan, bitolterol, nifedipine, phenobarbital, phentolamine, 13-cis retinoic acid, droprenilamine HCl, amlodipine, caffeine, zopiclone, tramadol HCl, pirbuterol, naloxone, meperidine HCl, trimethobenzamide, nalmefene, scopolamine, sildenafil, carbamazepine, procaterol HCl, methysergide, glutathione, olanzapine, zolpidem, levorphanol, buspirone and mixtures thereof. 6. The method of claim 1 wherein an inhalation dose of the compound is vaporized over a period of time no greater than 2 seconds. 7. The method of claim 1 wherein the mixing comprises passing the gas across the surface of the coating. 8. The method of claim 1 further comprising administering the resulting aerosol to a patient. 9. The method of claim 1 wherein the stable concentration is about 10.sup.9 particles/cc. 10. A method for generating an aerosol comprising the steps of: (a) depositing a coating comprising a physiologically active compound onto a substrate comprising dissolving the compound in an organic solvent, applying the solution to all or a portion of the substrate and allowing the solvent to evaporate; (b) heating a coating comprising a therapeutic amount of said physiologically active compound deposited onto said substrate to vaporize at least a portion of the compound, following said evaporation; (c) cooling the resulting vapor by mixing the vapor with a gas in a predetermined ratio, selected to form an aerosol comprised of particles within a desired size range when a stable concentration of particles in the gas is reached. 11. The method of claim 10 wherein the desired size range is a mass median aerodynamic diameter between about 1 to 3 microns. 12. The method of claim 10 wherein the desired size range is a mass median aerodynamic diameter between about 10 to 100 nanometers. 13. The method of claim 10 wherein the gas is air. 14. The method of claim 10 wherein an inhalation dose of the compound is vaporized over a period of time no greater than 2 seconds. 15. The method of claim 10 wherein the mixing comprises passing the gas across the surface of the coating. 16. The method of claim 10 further comprising administering the resulting aerosol to a patient. 17. The method of claim 10 wherein the stable concentration is about 10.sup.9 particles/cc. 18. A method for generating an aerosol comprising the steps of: (a) depositing a coating comprising a physiologically active compound onto a substrate comprising dissolving the compound in an organic solvent, applying the solution to all or a portion of the substrate and allowing the solvent to evaporate (b) heating the physiologically active compound to vaporize at least a portion of the compound, following said evaporation; (c) cooling the resulting vapor by mixing the vapor with a gas in a predetermined ratio, selected to form an aerosol comprised of particles within a desired size range that are sufficiently stable that they will remain within that range during the time necessary to administer the aerosol to a patient. 19. The method of claim 18 wherein the desired size range is a mass median aerodynamic diameter between about 1 to 3 microns. 20. The method of claim 18 wherein the desired size range is a mass median aerodynamic diameter between about 10 to 100 nanometers. 21. The method of claim 18 wherein the gas is air. 22. The method of claim 18 wherein the compound is selected from the group consisting of cannabinoid extracts from cannabis, THC, ketorolac, fentanyl, morphine, testosterone, ibuprofen, codeine, nicotine, Vitamin A, Vitamin E acetate, Vitamin E, nitroglycerin, pilocarpine, mescaline, testosterone enanthate, menthol, phencaramide, methsuximide, eptastigmine, promethazine, procaine, retinol, lidocaine, trimeprazine, isosorbide dinitrate, timolol, methyprylon, etamiphyllin, propoxyphene, salmetrol, vitamin E succinate, methadone, oxprenolol, isoproterenol bitartrate, etaqualone, Vitamin D3, ethambutol, ritodrine, omoconazole, cocaine, lomustine, ketamine, ketoprofen, cilazaprol, propranolol, sufentanil, metaproterenol, pentoxapylline, captopril, loxapine, cyproheptidine, carvediol, trihexylphenadine, alprostadil, melatonin, testosterone proprionate, valproic acid, acebutolol, terbutaline, diazepam, topiramate, pentobarbital, alfentanil HCl, papaverine, nicergoline, fluconazole, zafirlukast, testosterone acetate, droperidol, atenolol, metoclopramide, enalapril, albuterol, ketotifen, isoproterenol, amidarone HCl, zileuton, midazolam, oxycodone, cilostazol, propofol, nabilone, gabapentin, famotidine, lorezepam, naltrexone, acetaminophen, sumatriptan, bitolterol, nifedipine, phenobarbital, phentolamine, 13-cis retinoic acid, droprenilamine HCl, amlodipine, caffeine, zopiclone, tramadol HCl, pirbuterol, naloxone, meperidine HCl, trimethobenzamide, nalmefene, scopolamine, sildenafil, carbamazepine, procaterol HCl, methysergide, glutathione, olanzapine, zolpidem, levorphanol, buspirone and mixtures thereof. 23. The method of claim 18 wherein an inhalation dose of the compound is vaporized over a period of time no greater than 2 seconds. 24. The method of claim 18 wherein the mixing comprises passing the gas across the surface of the coating. 25. The method of claim 18 further comprising administering the resulting aerosol to a patient. 26. A method for generating an aerosol comprising the steps of: (a) depositing a coating comprising a compound onto a substrate comprising dissolving the compound in an organic solvent, applying the solution to all or a portion of the substrate and allowing the solvent to evaporate; (b) heating a coating comprising a therapeutic amount of a physiologically active compound deposited onto said substrate to vaporize at least a portion of the compound, following said evaporation; (c) cooling the resulting vapor by mixing the vapor with a gas in a predetermined ratio, selected to form an aerosol comprised of particles within a desired size range that are sufficiently stable that they will remain within that range during the time necessary to administer the aerosol to a patient. 27. The method of claim 26 wherein the particle size is a mass median aerodynamic diameter between about 1 to 3 microns. 28. The method of claim 26 wherein the particle size is a mass median aerodynamic diameter between about 10 to 100 nanometers. 29. The method of claim 26 wherein the gas is air. 30. The method of claim 26 wherein an inhalation dose of the compound is vaporized over a period of time no greater than 2 seconds. 31. The method of claim 26 wherein the mixing comprises passing the gas across the surface of the coating. 32. The method of claim 26 further comprising administering the resulting aerosol to a patient.