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

• US 20030185761A1
• Filed: 08/29/2002
• Published: 10/02/2003
• Est. Priority Date: 10/01/1997
• Status: Abandoned Application

• Current Assignee: NovaDel Pharma Inc.
• Original Assignee: NovaDel Pharma Inc.
• Inventors: Dugger, Harry A. III
• Application Number:
  US10/230,059
• Publication Number:
  US 20030185761A1
• Time in Patent Office: Days
• US Class Current: 424/43
• CPC Class Codes: A61K 31/085 having an ether linkage to aromatic ring nuclear carbon
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/421 1,3-Oxazoles, e.g. pemoline, trimethadione
• CPC Class Codes: A61K 31/433 Thidiazoles
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents

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.

Claims

1. A propellant free buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:

an active compound in an amount of between 0.001 and 60 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof; and

a polar solvent in an amount between 30 and 99 percent by weight of the total composition.

2. The composition of claim 1, further comprising a flavoring agent in an amount of between 0.1 and 10 percent by weight of the total composition.

3. The composition of claim 2, wherein the polar solvent is present in an amount between 37 and 98 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.

4. The composition of claim 3, wherein the polar solvent is present in an amount between 60 and 97 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.

5. The composition of claim 1, wherein the polar solvent is selected from the group consisting of polyethylene glycols having a molecular weight between 400 and 1000, C₂ to C₈ mono- and poly-alcohols, and C₇ to C₁₈, alcohols of linear or branched configuration.

6. The composition of claim 1, wherein the polar solvent comprises aqueous polyethylene glycol.

7. The composition of claim 1, wherein the polar solvent comprises aqueous ethanol.

8. The composition of claim 1, wherein the active compound is an anti-opioid agent selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof.

9. The composition of claim 1, wherein the active compound is an anti-migraine agent selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof.

10. The composition of claim 1, wherein the active compound is a pain control agent selected from the group consisting of non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof.

11. The composition of claim 1, wherein the active compound is an anesthetic selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocaine, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof.

12. The composition of claim 2, 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.

13. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim 1.

14. The method of claim 13, wherein the amount of the spray is predetermined.

15. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:

an active compound in an amount of between 0.1 and 25 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof;

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 C₃ to C₈ hydrocarbon of linear or branched configuration.

16. The composition of claim 15, further comprising a flavoring agent in an amount between 0.05 and 10 percent by weight of the total composition.

17. The composition of claim 16, wherein the polar solvent is present in an amount between 20 and 97 percent by weight of the total composition, the active compound 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 flavoring agent is present in an amount between 0.1 and 5 percent by weight of the total composition.

18. The composition of claim 17, wherein the polar solvent is present in an amount between 25 and 97 percent by weight of the total composition, the active compound 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 flavoring agent is present in an amount between 0.1 and 2.5 percent by weight of the total composition.

19. The composition of claim 15, wherein the polar solvent is selected from the group consisting of polyethyleneglycols having a molecular weight between 400 and 1000, C₂ to C₈ mono- and poly-alcohols, and C₇ to C₁₈ alcohols of linear or branched configuration.

20. The composition of claim 19, wherein the polar solvent comprises aqueous polyethylene glycol.

21. The composition of claim 19, wherein the polar solvent comprises aqueous ethanol.

22. The composition of claim 15, wherein the active compound is an anti-opioid agent selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof.

23. The composition of claim 15, wherein the active compound is an anti-migraine agent selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof.

24. The composition of claim 15, wherein the active compound is a pain control agent selected from the group consisting of non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof.

25. The composition of claim 15, wherein the active compound is an anesthetic selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocaine, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof.

26. The composition of claim 16, 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.

27. The composition of claim 15, wherein the propellant is selected from the group consisting of propane, N-butane, iso-butane, N-pentane, iso-pentane, neo-pentane, and mixtures thereof.

28. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim 15.

29. The method of claim 28, wherein the amount of the spray is predetermined.

30. A propellant free buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:

an active compound in an amount between 0.005 and 55 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof; and

a non-polar solvent in an amount between 30 and 99 percent by weight of the total composition.

31. The composition of claim 30, further comprising a flavoring agent in an amount between 0.1 and 10 percent by weight of the total composition.

32. The composition of claim 30, wherein the active compound is an anti-opioid agent selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof.

33. The composition of claim 30, wherein the active compound is an anti-migraine agent selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof.

34. The composition of claim 30, wherein the active compound is a pain control agent selected from the group consisting of non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof.

35. The composition of claim 30, wherein the active compound is an anesthetic selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocaine, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof.

36. The composition of claim 31, 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.

37. The composition of claim 30, wherein the solvent is selected from the group consisting of (C₂-C₂₄) fatty acid (C₂-C₆) esters, C₇-C₁₈ hydrocarbons of linear or branched configuration, C₂-C₆ alkanoyl esters, and triglycerides of C₂-C₆ carboxylic acids.

38. The composition of claim 37, wherein the solvent is miglyol.

39. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim 30.

40. The method of claim 39, wherein the amount of the spray is predetermined.

41. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:

an active compound in an amount between 0.05 and 50 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof; 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 C₃ to C₈ hydrocarbon of linear or brancehed configuration.

42. The composition of claim 41, further comprising a flavoring agent in an amount of between 0.1 and 10 percent by weight of the total composition.

43. The composition of claim 42, 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.

46. The composition of claim 42, wherein the propellant is selected from the group consisting of propane, n-butane, iso-butane, n-pantane, iso-pentane, neo-pentane, and mixtures thereof.

47. The composition of claim 46, 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.

48. The composition of claim 41, wherein the solvent is selected from the group consisting of (C₂-C₂₄) fatty acid (C₂-C₆) esters, C₇-C₁₈ hydrocarbons of linear or branched configuration, C₂-C₆ alkanoyl esters, and triglycerides of C₂-C₆ carboxylic acids.

49. The composition of claim 48, wherein the solvent is miglyol.

50. The composition of claim 41, wherein the active compound is an anti-opioid agent selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof.

51. The composition of claim 41, wherein the active compound is an anti-migraine agent selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof.

52. The composition of claim 41, wherein the active compound is a pain control agent selected from the group consisting of non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof.

53. The composition of claim 41, wherein the active compound is an anesthetic selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocaine, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof.

54. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim 41.

55. The method of claim 54, wherein the amount of the spray is predetermined.

44. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:

an active compound in an amount between 0.01 and 40 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof; and

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 C₃ to C₈ hydrocarbon of linear or brancehed configuration; and

A flavoring agent is present in an amount between 1 and 8 percent by weight of the total composition.

45. The composition of claim 44, 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 active compound is present in an amount from between 0.25 and 35 percent by weight of the total composition, and the flavoring agent is present in an amount between 2 and 7.5 percent by weight of the total composition.