TRANSDERMAL, ALCOHOL-FREE, PHARMACEUTICAL COMPOSITIONS

• US 20090098069A1
• Filed: 09/12/2008
• Published: 04/16/2009
• Est. Priority Date: 09/14/2007
• Status: Abandoned Application

• Current Assignee: Lumara Health IP Ltd. (Apollo Global Management, Inc.)
• Original Assignee: DrugTech Corporation (PD International Holdings LLC)
• Inventors: Vacca, Rita Downard
• Application Number:
  US12/209,864
• Publication Number:
  US 20090098069A1
• Time in Patent Office: Days
• US Class Current: 424/59
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 47/08 containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

An alcohol-free, transdermal drug delivery composition administered via a metered spray drug delivery device is described herein. The non-occlusive transdermal drug delivery composition includes a therapeutically effective amount of at least one physiologically active agent or prodrug thereof, an effective amount of at least one dermal penetration enhancer; and at least one non-volatile liquid. The transdermal drug delivery composition is administered to a dermal or mucosal surface of an animal needing the same using a metered spray device capable of delivering a fine spray of substantially uniform particle size to minimize the required drying time therefor.

Claims

1. An alcohol-free composition comprising:

an effective amount of one or more physiologically active agents;

an effective amount of one or more dermal penetration enhancers selected from the group consisting of ethers of diethylene glycol and ester sunscreens; and

one or more non-volatile liquids in an alcohol-free composition.

3. The composition of claim 1 wherein said active agents are selected from the group consisting of androgens, anti-androgens, estrogens, anti-estrogens, progestogens, anti-progestogens, adrenergic agonists, analgesics, sedatives, amides, arylpiperazines, nerve agents, antineoplastics, anti-inflammatory agents, anticholinergics, anticonvulsants, antidepressants, antiepileptics, antihistaminics, antihypertensives, muscle relaxants, diuretics, bronchodilators, and glucocorticoids.

4. The composition of claim 1 wherein said active agents are selected from the group consisting of alimentary agents, cardiovascular agents, blood and haemopoietic agents, central nervous system agents, musculoskeletal agents, hormones, steroids, genitourinary agents, antimicrobials, metabolism agents, allergy and immune system agents and respiratory agents.

5. The composition of claim 1 wherein said active agent is 17-β

-oestradiol.

6. The composition of claim 1 wherein said dermal penetration enhancers are selected from the group consisting of ether sunscreen penetration enhancers, mono C_1-6 alkyl ethers of diethylene glycol, laurocapram derivatives, laurocapram derivatives, oleic acid and its ester derivatives, sorbitan esters, fatty acid esters, esters of 2-pyrrolidone and 2-n-nonyl-1-3-dioxolane.

7. The composition of claim 1 wherein said dermal penetration enhancer is an ether of diethylene glycol.

8. The composition of claim 1 wherein said non-volatile liquids are selected from the group consisting of deionized water, water, glycerides, vegetable oils, mineral oils, silicone oils, animal oils and benzoates.

9. The composition of claim 1 wherein said non-volatile liquid is water or deionized water.

10. The composition of claim 1 wherein said active agent is present in an amount ranging from about 0.1 to about 15 weight percent.

11. The composition of claim 1 wherein said dermal permeation enhancer is present in an amount ranging from about 0.1 to about 60 weight percent.

12. The composition of claim 1 wherein said non-volatile liquid is present in an amount up to about 65 weight percent.

13. The composition of claim 1 wherein said composition additionally includes one or more propellants.

14. The composition of claim 1 wherein said composition additionally includes one or more propellants selected from the group consisting of dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide and dimethyl ether.

15. The composition of claim 1 wherein said composition additionally includes a carbon dioxide or dimethyl ether propellant.

53. A method for the treatment or prophylaxis of a disease or condition in an animal which comprises administering to a dermal or mucosal surface of said animal in need of such treatment a therapeutically effective amount of the composition of claim 1.

54. The method according to claim 53, wherein the disease or condition requires male hormone replacement therapy or requires female hormone replacement therapy.

55. The method according to claim 53, wherein the disease or condition is soft tissue injury, narcotic withdrawal, severe post-operative pain, motion sickness, oestrogen dependent breast cancer, prostatic enlargement and/or prostatic cancer, alopecia and acne, anxiety disorders, male impotence, Raynauds syndrome and varicose veins, sleep disorders, jetlag, herpes virus infections, deep vein thrombosis, migraine, high blood pressure, malaria, diagnosis of cystic fibrosis, asthma or nocturnal asthma.

2. A drug delivery device comprising:

an effective amount of one or more physiologically active agents;

an effective amount of one or more dermal penetration enhancers; and

a non-volatile liquid in an alcohol-free composition contained within a valve-actuated metered spray drug delivery device.

16. The device of claim 2 wherein said active agents are selected from the group consisting of androgens, anti-androgens, estrogens, anti-estrogens, progestogens, anti-progestogens, adrenergic agonists, analgesics, sedatives, amides, arylpiperazines, nerve agents, antineoplastics, anti-inflammatory agents, anticholinergics, anticonvulsants, antidepressants, antiepileptics, antihistaminics, antihypertensives, muscle relaxants, diuretics, bronchodilators, and glucocorticoids.

17. The device of claim 2 wherein said active agent is selected from the group consisting of alimentary agents, cardiovascular agents, blood and haemopoietic agents, central nervous system agents, musculoskeletal agents, hormones, steroids, genitourinary agents, antimicrobials, metabolism agents, allergy and immune system agents and respiratory agents.

18. The device of claim 2 wherein said active agent is 17-□

-oestradiol.

19. The device of claim 2 wherein said dermal penetration enhancers are selected from the group consisting of ether sunscreen penetration enhancers, mono C1-6 alkyl ethers of diethylene glycol, laurocapram derivatives, laurocapram derivatives, oleic acid and its ester derivatives, sorbitan esters, fatty acid esters, esters of 2-pyrrolidone and 2-n-nonyl-1-3-dioxolane.

20. The device of claim 2 wherein said dermal penetration enhancer is an ether of diethylene glycol.

21. The device of claim 2 wherein said non-volatile liquids are selected from the group consisting of deionized water, water, glycerides, vegetable oils, mineral oils, silicone oils, animal oils and benzoates.

22. The device of claim 2 wherein said non-volatile liquid is water or deionized water.

23. The device of claim 2 wherein said active agent is present in an amount ranging from 0.1 to 15 weight percent.

24. The device of claim 2 wherein said dermal permeation enhancer is present in an amount ranging from 0.1 to 60 weight percent.

25. The device of claim 2 wherein said non-volatile liquid is present in an amount up to about 65 weight percent.

26. The device of claim 2 wherein said composition additionally includes one or more propellants.

27. The device of claim 2 wherein said composition additionally includes one or more propellants selected from the group consisting of dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide and dimethyl ether.

28. The device of claim 2 wherein said composition additionally includes dimethyl ether or carbon dioxide as a propellant.

29. The device of claim 2 wherein said device includes a vapor tap dimensioned about 0.013 inches to about 0.020 inches.

30. The device of claim 2 wherein said device includes a stem orifice dimensioned about 0.010 inches to about 0.014 inches.

31. The device of claim 2 wherein said device includes a nozzle orifice dimensioned about 0.018+10 percent.

32. The device of claim 2 wherein said device upon actuation sprays said composition at a spray delivery rate of about 0.20 g/second to about 0.25 g/second.

33. The device of claim 2 wherein said device upon actuation sprays said composition with a particle size of approximately 50 microns.

34. A method of making an alcohol-free drug delivery composition comprising:

combining an effective amount of one or more physiologically

active agents;

an effective amount of one or more dermal penetration enhancers selected from the group consisting of ethers of diethylene glycol and ester sunscreens; and

one or more non-volatile liquids in an alcohol-free composition.

36. The method of claim 34 or 35 wherein said active agents are selected from the group consisting of androgens, anti-androgens, estrogens, anti-estrogens, progestogens, anti-progestogens, adrenergic agonists, analgesics, sedatives, amides, arylpiperazines, nerve agents, antineoplastics, anti-inflammatory agents, anticholinergics, anticonvulsants, antidepressants, antiepileptics, antihistaminics, antihypertensives, muscle relaxants, diuretics, bronchodilators, and glucocorticoids.

37. The method of claim 34 or 35 wherein said active agents are selected from the group consisting of alimentary agents, cardiovascular agents, blood and haemopoietic agents, central nervous system agents, musculoskeletal agents, hormones, steroids, genitourinary agents, antimicrobials, metabolism agents, allergy and immune system agents and respiratory agents.

38. The method of claim 34 or 35 wherein said active agent is 17-□

-oestradiol.

39. The method of claim 34 or 35 wherein said dermal penetration enhancers are selected from the group consisting of ether sunscreen penetration enhancers, mono C1-6 alkyl ethers of diethylene glycol, laurocapram derivatives, laurocapram derivatives, oleic acid and its ester derivatives, sorbitan esters, fatty acid esters, esters of 2-pyrrolidone and 2-n-nonyl-1-3-dioxolane.

40. The method of claim 34 or 35 wherein said dermal penetration enhancer is an ether of diethylene glycol.

41. The method of claim 34 or 35 wherein said non-volatile liquids are selected from the group consisting of deionized water, water, glycerides, vegetable oils, mineral oils, silicone oils, animal oils and benzoates.

42. The method of claim 34 or 35 wherein said non-volatile liquid is water or deionized water.

43. The method of claim 34 or 35 wherein said active agent is present in an amount ranging from about 0.1 to about 15 weight percent.

44. The method of claim 34 or 35 wherein said dermal permeation enhancer is present in an amount ranging from about 0.1 to about 60 weight percent.

45. The method of claim 34 or 35 wherein said non-volatile liquid is present in an amount up to about 65 weight percent.

46. The method of claim 34 or 35 wherein said composition additionally includes one or more propellants.

47. The method of claim 34 or 35 wherein said composition additionally includes one or more propellants selected from the group consisting of dichlorodifluoromethane, tichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide and dimethyl ether.

48. The method of claim 34 or 35 wherein said composition additionally includes dimethyl ether or carbon dioxide as a propellant.

35. A method of administering an alcohol-free drug delivery composition comprising:

spraying an effective amount of one or more physiologically

active agents;

an effective amount of one or more dermal penetration enhancers selected from the group consisting of ethers of diethylene glycol and ester sunscreens; and

one or more non-volatile liquids in an alcohol-free composition onto a dermal or mucosal surface.

49. The method of claim 35 wherein said surface is dry in less than 10 minutes.

50. The method of claim 35 wherein said surface is dry in less than 4 minutes.

51. The method of claim 35 wherein said surface is dry in less than 3 minutes.

52. The method of claim 35 wherein said surface is dry in less than 1 minute.

56. A non-occlusive, transdermal drug delivery composition which comprises:

(i) a therapeutically effective amount of at least one physiologically active agent;

(ii) at least one dermal penetration enhancer, which is present in an amount of from 10 to 10,000 wt % based on the weight of the active agent;

(iii) at least one non-volatile liquid present in an amount to act as a vehicle for the active agent and penetration enhancer;

wherein;

the dermal penetration enhancer (A) is adapted to transport the physiologically active agent across a dermal or mucosal surface of an animal, when the non-volatile liquid evaporates, to form a reservoir or depot of a mixture comprising the penetration enhancer and the physiologically active agent within said surface or membrane, and (B) is tolerated by the dermal or mucosal surface of the animal; and

,

after administration of the composition to an area of the dermal or mucosal surface, the area becomes dry within 4 minutes of application.

57. A composition according to claim 56, wherein the dermal or mucosal surface becomes dry within one minute of application.

58. A composition according to claim 56, wherein said dermal permeation enhancer is an alkyl para-aminobenzoate, alkyl dimethyl-para-aminobenzoate, alkyl cinnamate, alkyl methoxycinnamate or alkyl salicylate.

59. A composition according to claim 56, wherein said dermal penetration enhancer is octyl dimethyl-para-aminobenzoate, octyl para-methoxycinnamate or octyl salicylate.

60. A composition according to claim 56, wherein the non-volatile liquid is deionized water.

61. A composition according to claim 56, wherein the physiologically active agent is a steroid, hormone derivative, non-steroidal anti-inflammatory drug, opioid analgesic, antinauseant, antioestrogen, aromatase inhibitor, 5-alpha reductase inhibitor, anxiolytic, prostaglandin, anti-viral drug, anti-migraine compound, antihypertensive agent, anti-malarial compound, bronchodilator anti-depressant, anti-alzheimer'"'"'s agent, neuroleptic and antipsychotic agent, anti-parkinson'"'"'s agent, antiandrogen or anorectic agent.

62. A composition according to claim 56, wherein the physiologically active agent is testosterone, oestradiol, ethinyloestradiol, progesterone, norethisterone acetate, ibuprofen, ketoprofen, flurbiprofen, naproxen, diclofenac, fentanyl, buprenorphine, scopolamine, prochlorperazine, metochlopramide, ondansetron, tamoxifen, epitiostanol, exemestane, 4-hydroxy-androstenedione and its derivatives, finasteride, turosteride, LY191704, MK-306, alprazolam, alprostadil, prostacylcin and its derivatives, melatonin, n-docosanol, tromantadine, lipophilic pro-drugs of acyclovir, low molecular weight heparin, enoxaparin, sumatriptan, amlodipine, nitrendipine, primaquine, minoxidil, minoxidil pro-drugs, pilocarpine, salbutamol, terbutaline, salmeterol, ibogaine, bupropian, rolipram, tacrine, fluphenazine, haloperidol, N-0923, cyproterone acetate or mazindol.

63. A composition according to claim 56, wherein the composition is applied to a dermal surface by a metered aerosol spray.

64. A composition according to claim 56, wherein the aerosol is a fixed or variable metered dose aerosol.

65. A composition according to claim 56, further comprising a pharmaceutical compounding agent, co-solvent, surfactant, emulsifier, antioxidant, preservative, stabiliser, diluent or a mixture of two or more of said components.