Pharmaceutical composition and method for transdermal drug delivery

• US 20050025833A1
• Filed: 07/15/2004
• Published: 02/03/2005
• Est. Priority Date: 07/16/2003
• Status: Abandoned Application

• Current Assignee: Perrigo Israel Pharmaceuticals Limited (Perrigo Company PLC)
• Original Assignee: Perrigo Israel Pharmaceuticals Limited (Perrigo Company PLC)
• Inventors: Zeevi, Amira, Asculai, Eilon, Abu-Gnim, Chalil, Aschkenasy, Chaim, Chen, Oren, Boochnik, Rami
• Application Number:
  US10/891,486
• Publication Number:
  US 20050025833A1
• Time in Patent Office: Days
• US Class Current: 424/484
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone

Abstract

A pharmaceutical composition for transdermal administration of a hormone (e.g., testosterone), which includes a quaternary ammonium compound as a penetration enhancer, and methods utilizing same for treating medical conditions in which elevating a hormone serum level is beneficial are disclosed.

Claims

1. A hydroalcoholic gel pharmaceutical composition for topical application comprising a pharmaceutically active ingredient, a penetration enhancer, an alcohol and a gelling agent, wherein said pharmaceutically active ingredient is a hormone, and said penetration enhancer is a quaternary ammonium compound.

2. The hydroalcoholic gel pharmaceutical composition of claim 1, being capable, upon application of an amount of the composition onto at least one biological surface of a subject, of elevating a blood serum concentration of said hormone in said subject from a subpotent concentration to a potent concentration within about 24 hours after said application.

3. The hydroalcoholic gel pharmaceutical composition of claim 2, wherein said amount ranges between about 0.1 grams and about 10 grams.

4. The hydroalcoholic gel pharmaceutical composition of claim 2, wherein said amount ranges between about 3 milligrams and about 100 milligrams per square centimeter of said at least one biological surface.

5. The hydroalcoholic gel pharmaceutical composition of claim 4, wherein said amount ranges between about 4 milligrams and about 60 milligrams per square centimeter of said at least one biological surface.

6. The hydroalcoholic gel pharmaceutical composition of claim 1, wherein a concentration of said quaternary ammonium compound ranges between about 0.04 weight percentages and about 0.4 weight percentages.

7. The hydroalcoholic gel pharmaceutical composition of claim 6, wherein a concentration of said quaternary ammonium compound ranges between about 0.07 weight percentage and about 0.1 weight percentage.

8. The hydroalcoholic gel pharmaceutical composition of claim 1, wherein said quaternary ammonium compound is selected from the group consisting of benzalkonium chloride, benzethonium chloride, hexadecyltrethylammonium bromide, methylbenzethonium chloride, cetalkonium chloride, centrimonium bromide, domiphen bromide, domiphen chloride, domiphen fluoride, cetyl pyridinium chloride, dequalinium chloride, the cis isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride, cetyl trimethylammonium bromide, benzalkonium saccharinate;

behenalkonium chloride;

cetalkonium chloride;

erucalkonium chloride;

lauralkonium chloride;

myristalkonium chloride;

myristalkonium saccharinate (Quaternium-3);

stearalkonium chloride;

olealkonium chloride;

tallowalkonium chloride;

dodecylbenzyltrimethylammonium chloride (Quaternium-28);

dodecylbenzyl trimethyl ammonium 2-ethylhexanoate;

ethylbenzyl alkyldimethylammonium cyclohexylsulfanamate (Quaternium-8);

ethylbenzyl dimethyl dodecyl ammonium chloride (Quaternium-14);

dodecylbenzyl dimethyl octadecyl ammonium chloride;

dodecylbenzyl triethanol ammonium chloride (Quaternium-30);

benzoxonium chloride;

benzylbis(2-hydroxyethyl)(2-dodecyloxyethyl)ammonium bromide;

benzylbis(2-hydroxyethyl)(2-dodecyloxyethyl)ammonium chloride;

N,N-(diethyl-N-[2-[4-(1,1,3,3-tetramethylbutyl)phenoxy]ethyl] benzenemethanaminium chloride (phenoctide);

dodecarbonium chloride;

babassuamidopropalkonium chloride;

wheatgermamidopropalkonium chloride.

9. The hydroalcoholic gel pharmaceutical composition of claim 8, wherein said quaternary ammonium compound is benzalkonium chloride.

10. The hydroalcoholic gel pharmaceutical composition of claim 1, wherein said hormone is selected from the group consisting of an androgenic hormone, an estrogenic hormone and a progestogenic hormone.

11. The hydroalcoholic gel pharmaceutical composition of claim 10, wherein said hormone is selected from the group consisting of methyltestosterone, androsterone, androsterone acetate, androsterone propionate, androsterone benzoate, androsteronediol, androsteronediol-3-acetate, androsteronediol-17-acetate, androsteronediol 3-17-diacetate, androsteronediol-17-benzoate, androsteronedione, androstenedione, androstenediol, dehydrocpiandrosterone, sodium dehydroepiandrosterone sulfate, dromostanolone, dromostanolone propionate, ethylestrenol, fluoxymesterone, nandrolone phenpropionate, nandrolone decanoate, nandrolone furylpropionate, nandrolone cyclohexane-propionate, nandrolone benzoate, nandrolone cyclohexanecarboxylate, androsteronediol-3-acetate-1-7-benzoate, oxandrolone, oxymetholone, stanozolol, testosterone, testosterone decanoate, 4-dihydrotestosterone, 5α

-dihydrotestosterone, testolactone, 17α

-methyl-19-nortestosterone, desogestrel, dydrogesterone, ethynodiol diacetate, medroxyprogesterone, levonorgestrel, medroxyprogesterone acetate, hydroxyprogesterone caproate, norethindrone, norethindrone acetate, norethynodrel, allylestrenol, 19-nortestosterone, lynoestrenol, quingestanol acetate, medrogestone, norgestrienone, dimethisterone, ethisterone, cyproterone acetate, chlormadinone acetate, megestrol acetate, norgestimate, norgestrel, desogrestrel, trimegestone, gestodene, nomegestrol acetate, progesterone, 5α

-pregnan-3β

,20α

-diol sulfate, 5α

-pregnan-3β

,20β

-diol sulfate, 5α

-pregnan-3β

-ol-20-one, 16,5α

-pregnen-3β

-ol-20-one, 4-pregnen-20β

-ol-3-one-20-sulfate, acetoxypregnenolone, anagestone acetate, cyproterone, dihydrogesterone, flurogestone acetate, gestadene, hydroxyprogesterone acetate, hydroxymethylprogesterone, hydroxymethyl progesterone acetate, 3-ketodesogestrel, megestrol, melengestrol acetate, norethisterone, estrone, estradiol and estriol, progesterone, pharmaceutically acceptable esters thereof, salts thereof, and combinations of any of the foregoing.

12. The hydroalcoholic gel pharmaceutical composition of claim 11, wherein said hormone is testosterone.

13. The hydroalcoholic gel pharmaceutical composition of claim 1, wherein a concentration of said hormone ranges between about 0.5 weight percentages and about 5 weight percentages.

14. The hydroalcoholic gel pharmaceutical composition of claim 13, wherein a concentration of said hormone is about 1 weight percentage.

15. The hydroalcoholic gel pharmaceutical composition of claim 1, wherein said alcohol is a C2-C4 alcohol.

16. The hydroalcoholic gel pharmaceutical composition of claim 15, wherein said C2-C4 alcohol is selected from the group comprising ethanol and isopropanol.

17. The hydroalcoholic gel pharmaceutical composition of claim 16, wherein said C2-C4 alcohol is ethanol.

18. The hydroalcoholic gel pharmaceutical composition of claim 15, wherein a concentration of said C2-C4 alcohol ranges between about 40 weight percentages and about 90 weight percentages.

19. The hydroalcoholic gel pharmaceutical composition of claim 18, wherein a concentration of said C2-C4 alcohol ranges between about 55 weight percentages and about 70 weight percentages.

20. The hydroalcoholic gel pharmaceutical composition of claim 19, wherein a concentration of said C2-C4 alcohol is about 69 weight percentages.

21. The hydroalcoholic gel pharmaceutical composition of claim 1, wherein said gelling agent is selected from the group consisting of a polymeric thickening agent, a fatty alcohol, a fatty acid, and a fatty acid alkali salt, an inorganic gelling agent and any mixture thereof.

22. The hydroalcoholic gel pharmaceutical composition of claim 1, wherein said gelling agent comprises a polyacrylic acid.

23. The hydroalcoholic gel pharmaceutical composition of claim 21, wherein said polymeric thickening agent comprises a cellulosic ether.

24. The hydroalcoholic gel pharmaceutical composition of claim 23, wherein said cellulosic ether is selected from the group consisting of carboxymethylcellulose, hydroxypropyl cellulose and hydroxyethylcellulose.

25. The hydroalcoholic gel pharmaceutical composition of claim 21, wherein said polymeric thickening agent is selected from the group consisting of xanthan gum and guar gum.

26. The hydroalcoholic gel pharmaceutical composition of claim 1, wherein a concentration of said gelling agent ranges between about 0.1 weight percentage and about 5 weight percentages.

27. The hydroalcoholic gel pharmaceutical composition of claim 26, wherein a concentration of said gelling agent ranges between about 0.1 weight percentage and about 2 weight percentages.

28. The hydroalcoholic gel pharmaceutical composition of claim 1, further comprising a penetration co-enhancer.

29. The hydroalcoholic gel pharmaceutical composition of claim 28, wherein said penetration co-enhancer is a glycol.

30. The hydroalcoholic gel pharmaceutical composition of claim 1, further comprising an additional pharmaceutically active ingredient.

31. The hydroalcoholic gel pharmaceutical composition of claim 1, further comprising at least one additive.

32. The hydroalcoholic gel pharmaceutical composition of claim 31, wherein said at least one additive is selected from the group consisting of a moisturizing agent and an emollient.

33. The hydroalcoholic gel pharmaceutical composition of claim 31, wherein a concentration of said at least one additive ranges between about 1 weight percentage and about 5 weight percentages.

34. The hydroalcoholic gel pharmaceutical composition of claim 31, wherein said at least one additive comprises glycerin.

35. The hydroalcoholic gel pharmaceutical composition of claim 32, wherein said emollient is selected from the group comprising dodecane, squalane, cholesterol, isohexadecane, isononyl isononanoate, PPG Ethers, petrolatum, lanolin, safflower oil, castor oil, coconut oil, cottonseed oil, palm kernel oil, palm oil, peanut oil, soybean oil, polyol carboxylic acid esters, derivatives thereof and mixtures thereof.

36. The hydroalcoholic gel pharmaceutical composition of claim 31, wherein said at least one additive is selected from the group consisting of a humectant, a deodorant agent, an antiperspirant, a stabilizing agent, a pH adjusting agent, a preservative, an emulsifier, an occlusive agent, a solubilizing agent, a colorant, and a surfactant.

37. The hydroalcoholic gel pharmaceutical composition of claim 1, packaged in a packaging material and identified in print, in or on said packaging material, for use in the treatment of a medical condition in which elevating a serumn hormone level in a subject is beneficial.

38. The hydroalcoholic gel pharmaceutical composition of claim 37, wherein said subject is a human male.

39. The hydroalcoholic gel pharmaceutical composition of claim 38, wherein said medical condition is selected from the group consisting of primary hypogonadism, secondary hypogonadism, age-related hypogonadism, hormone deficiency, erectile dysfunction, AIDS wasting syndrome, reduced sex drive, energy loss, loss of bone mass, extreme tiredness, low energy, and depression.

40. The hydroalcoholic gel pharmaceutical composition of claim 37, wherein said subject is a human female.

41. The hydroalcoholic gel pharmaceutical composition of claim 40, wherein said medical condition is selected from the group consisting of breast cancer, postpartum breast pain or engorgement, reduced sex drive, menopausal symptoms, energy loss, loss of bone mass, extreme tiredness, low energy, and depression.

42. The hydroalcoholic gel pharmaceutical composition of claim 40, wherein said human female is selected from the group consisting of young oophorectomized/hysterectomized women, post-menopausal women on estrogen replacement therapy, women on oral contraceptives, women with adrenal dysfunction, women with corticosteroid-induced adrenal suppression, and human immunodeficiency virus-positive women.

43. A hydroalcoholic gel pharmaceutical composition for topical application comprising testosterone, benzalkonium chloride, a C2-C4 alcohol and a gelling agent.

44. The hydroalcoholic gel pharmaceutical composition of claim 43, being capable, upon application of an amount of the composition onto at least one biological surface of a subject, of elevating a blood serum concentration of said testosterone in said subject from a subpotent concentration to a potent concentration within about 24 hours after said application.

45. The hydroalcoholic gel pharmaceutical composition of claim 44, wherein said amount ranges between about 0.1 grams and about 10 grams.

46. The hydroalcoholic gel pharmaceutical composition of claim 43, wherein a concentration of said benzalkonium chloride ranges between about 0.04 weight percentages and about 0.4 weight percentages.

47. The hydroalcoholic gel pharmaceutical composition of claim 46, wherein a concentration of said benzalkonium chloride ranges between about 0.07 weight percentage and about 0.1 weight percentages.

48. The hydroalcoholic gel pharmaceutical composition of claim 43, wherein a concentration of said testosterone ranges between about 0.5 and about 5 weight percentages.

49. The hydroalcoholic gel pharmaceutical composition of claim 48, wherein a concentration of said testosterone is about 1 weight percentage.

50. The hydroalcoholic gel pharmaceutical composition of claim 43, wherein said C2-C4 alcohol is selected from the group comprising ethanol and isopropanol.

51. The hydroalcoholic gel pharmaceutical composition of claim 50, wherein said C2-C4 alcohol is ethanol.

52. The hydroalcoholic gel pharmaceutical composition of claim 43, wherein a concentration of said C2-C4 alcohol ranges between about 40 weight percentages and about 90 weight percentages.

53. The hydroalcoholic gel pharmaceutical composition of claim 52, wherein a concentration of said C2-C4 alcohol ranges between about 55 weight percentages and about 70 weight percentages.

54. The hydroalcoholic gel pharmaceutical composition of claim 53, wherein a concentration of said C2-C4 alcohol is about 69 weight percentages.

55. The hydroalcoholic gel pharmaceutical composition of claim 43, wherein said gelling agent is selected from the group consisting of a polymeric thickening agent, a fatty alcohol, a fatty acid, and a fatty acid alkali salt, an inorganic gelling agent and any mixture thereof.

56. The hydroalcoholic gel pharmaceutical composition of claim 43, wherein said gelling agent comprises a polyacrylic acid.

57. The hydroalcoholic gel pharmaceutical composition of claim 43, further comprising an additional pharmaceutically active ingredient.

58. The hydroalcoholic gel pharmaceutical composition of claim 43, packaged in a packaging material and identified in print, in or on said packaging material, for use in the treatment of a medical condition in which elevating a serum hormone level in a subject is beneficial.

59. The hydroalcoholic gel pharmaceutical composition of claim 58, wherein said subject is a human male.

60. The hydroalcoholic gel pharmaceutical composition of claim 59, being capable, upon application of an amount of the composition onto at least one biological surface of said male subject, of elevating a blood serum concentration of said testosterone in said human male to a value ranging between about 300 ng/dl and about 1100 ng/dl, within 24 hours after said application.

61. The hydroalcoholic gel pharmaceutical composition of claim 59, wherein said medical condition is selected from the group consisting of primary hypogonadism, secondary hypogonadism, age-related hypogonadism, hormone deficiency, erectile dysfunction, AIDS wasting syndrome, reduced sex drive, energy loss, loss of bone mass,extreme tiredness, low energy, and depression.

62. The hydroalcoholic gel pharmaceutical composition of claim 58, wherein said subject is a human female.

63. The hydroalcoholic gel pharmaceutical composition of claim 62, wherein said medical condition is selected from the group consisting of breast cancer, postpartum breast pain or engorgement, reduced sex drive, menopausal symptoms, energy loss, loss of bone mass, extreme tiredness, low energy, and depression.

64. The hydroalcoholic gel pharmaceutical composition of claim 62, wherein said human female is selected from the group consisting of young oophorectomized/hysterectomized women, post-menopausal women on estrogen replacement therapy, women on oral contraceptives, women with adrenal dysfunction, women with corticosteroid-induced adrenal suppression, and human immunodeficiency virus-positive women.

65. A method of transdermally delivering a hormone to the blood serum of a subject, the method comprising:

providing a hydroalcoholic gel pharmaceutical composition for topical application including said hormone, a quaternary ammonium compound, an alcohol and a gelling agent; and

contacting an amount of said topical pharmaceutical composition with at least one biological surface of said subject, to thereby deliver said hormone to said blood serum through said biological surface.

66. The method of claim 65, wherein said amount of said pharmaceutical hydroalcoholic gel composition ranges between about 0.1 gram and about 10 grams.

67. The method of claim 65, wherein said amount of said hydroalcoholic gel pharmaceutical composition ranges between about 3 milligrams and about 100 milligrams per square centimeter of said at least one biological surface.

68. The method of claim 67, wherein said amount ranges between about 4 milligrams and about 60 milligrams per square centimeter of said at least one biological surface.

69. The method of claim 65, wherein a concentration of said hormone in said blood serum of said subject is elevated from a subpotent concentration to a potent concentration within about 24 hours after said contacting.

70. The method of claim 65, wherein said at least one biological surface is selected from the group consisting of the abdomen, an armpit, an inside arm, the back, a thigh, a shoulder, and the scrotum.

71. The method of claim 65, wherein a concentration of said quaternary ammonium compound ranges between about 0.04 weight percentages and about 0.4 weight percentages.

72. The method of claim 71, wherein a concentration of said quaternary ammonium compound ranges between about 0.07 weight percentages and about 0.1 weight percentages.

73. The method of claim 65, wherein said quaternary ammonium compound is selected from the group consisting of benzalkonium chloride, benzethonium chloride, cetrimide, and methylbenzethonium chloride hexadecyltrethylammonium bromide, methylbenzethonium chloride, cetalkonium chloride, centrimonium bromide, domiphen bromide, domiphen chloride, domiphen fluoride, cetyl pyridinium chloride, dequalinium chloride, the cis isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride, cetyl trimethylammonium bromide, benzalkonium saccharinate;

behenalkonium chloride;

cetalkonium chloride;

erucalkonium chloride;

lauralkonium chloride;

myristalkonium chloride;

myristalkonium saccharinate (Quaternium-3);

stearalkonium chloride;

olealkonium chloride;

tallowalkonium chloride;

dodecylbenzyltrimethylammonium chloride (Quaternium-28);

dodecylbenzyl trimethyl ammonium 2-ethylhexanoate;

ethylbenzyl alkyldimethylammonium cyclohexylsulfanamate (Quaternium-8);

ethylbenzyl dimethyl dodecyl ammonium chloride (Quaternium-14);

dodecylbenzyl dimethyl octadecyl ammonium chloride;

dodecylbenzyl triethanol ammonium chloride (Quaternium-30);

benzoxonium chloride;

benzylbis(2-hydroxyethyl)(2-dodecyloxyethyl)ammonium bromide;

benzylbis(2-hydroxyethyl)(2-dodecyloxyethyl)ammonium chloride;

N,N-(diethyl-N-[2-[4-(1,1,3,3-tetramethylbutyl)phenoxy]ethyl] benzenemethanaminium chloride (phenoctide);

dodecarbonium chloride;

babassuamidopropalkonium chloride;

wheatgermamidopropalkonium chloride.

74. The method of claim 73, wherein said quaternary ammonium compound is benzalkonium chloride.

75. The method of claim 65, wherein said hormone is selected from the group consisting of an androgenic hormone, an estrogenic hormone and a progestogenic hormone.

76. The method of claim 75, wherein said hormone is selected from the group consisting of methyltestosterone, androsterone, androsterone acetate, androsterone propionate, androsterone benzoate, androsteronediol, androsteronediol-3-acetate, androsteronediol-17-acetate, androsteronediol 3-17-diacetate, androsteronediol-17-benzoate, androsteronedione, androstenedione, androstenediol, dehydroepiandrosterone, sodium dehydroepiandrosterone sulfate, dromostanolone, dromostanolone propionate, ethylestrenol, fluoxymesterone, nandrolone phenpropionate, nandrolone decanoate, nandrolone furylpropionate, nandrolone cyclohexane-propionate, nandrolone benzoate, nandrolone cyclohexanecarboxylate, androsteronediol-3-acetate-1-7-benzoate, oxandrolone, oxymetholone, stanozolol, testosterone, testosterone decanoate, 4-dihydrotestosterone, 5α

-dihydrotestosterone, testolactone, 17α

-methyl-19-nortestosterone, desogestrel, dydrogesterone, ethynodiol diacetate, medroxyprogesterone, levonorgestrel, medroxyprogesterone acetate, hydroxyprogesterone caproate, norethindrone, norethindrone acetate, norethynodrel, allylestrenol, 19-nortestosterone, lynoestrenol, quingestanol acetate, medrogestone, norgestrienone, dimethisterone, ethisterone, cyproterone acetate, chlormadinone acetate, megestrol acetate, norgestimate, norgestrel, desogrestrel, trimegestone, gestodene, nomegestrol acetate, progesterone, 5α

-pregnan-3β

,20α

-diol sulfate, 5α

-pregnan-3β

,20β

-diol sulfate, 5α

-pregnan-3β

-ol-20-one, 16,5α

-pregnen-3β

-ol-20-one, 4-pregnen-20β

-ol-3-one-20-sulfate, acetoxypregnenolone, anagestone acetate, cyproterone, dihydrogesterone, flurogestone acetate, gestadene, hydroxyprogesterone acetate, hydroxymethylprogesterone, hydroxymethyl progtesterone acetate, 3-ketodesogestrel, megestrol, melengestrol acetate, norethisterone, estrone, estradiol and estriol, progesterone, pharmaceutically acceptable esters, salts thereof, and combinations of any of the foregoing.

77. The method of claim 76, wherein said hormone is testosterone.

78. The method of claim 65, wherein a concentration of said hormone ranges between about 0.5 weight percentages and about 5 weight percentages of the total weight of said composition.

79. The method of claim 78, wherein a concentration of said hormone is about 1 weight percentage of the total weight of said composition.

80. The method of claim 65, wherein said alcohol is a C2-C4 alcohol.

81. The method of claim 80, wherein said C2-C4 alcohol is selected from the group comprising ethanol and isopropanol.

82. The method of claim 81, wherein said C2-C4 alcohol is ethanol.

83. The method of claim 80, wherein a concentration of said C2-C4 alcohol ranges between about 40 weight percentages and about 90 weight percentages of the total weight of said composition.

84. The method of claim 83, wherein a concentration of said C2-C4 alcohol ranges between about 55 weight percentages and about 70 weight percentages of the total weight of said composition.

85. The method of claim 84, wherein a concentration of said C2-C4 alcohol is about 69 weight percentages of the total weight of said composition.

86. The method of claim 65, wherein said gelling agent is selected from the group consisting of a polymeric thickening agent, a fatty alcohol, a fatty acid, and a fatty acid alkali salt, an inorganic gelling agent and any mixture thereof.

87. The method of claim 65, wherein said gelling agent comprises a polyacrylic acid.

88. The method of claim 86, wherein said polymeric thickening agent comprises a cellulosic ether.

89. The method of claim 88, wherein said cellulosic ether is selected from the group consisting of carboxymethylcellulose, hydroxypropyl cellulose and hydroxyethylcellulose.

90. The method of claim 86, wherein said polymeric thickening agent is selected from the group consisting of xanthan gum and guar gum.

91. The method of claim 65, wherein a concentration of said gelling agent ranges between about 0.1 weight percentage and about 5 weight percentages of the total weight of said composition.

92. The method of claim 91, wherein a concentration of said gelling agent ranges between about 0.1 weight percentage and about 2 weight percentages of the total weight of said composition.

93. The method of claim 65, wherein said pharmaceutical composition further comprises a penetration co-enhancer.

94. The method of claim 93, wherein said penetration co-enhancer is a glycol.

95. The method of claim 65, wherein said pharmaceutical composition further comprises an additional pharmaceutically active ingredient.

96. The method of claim 65, wherein said pharmaceutical composition further comprises at least one additive.

97. The method of claim 96, wherein said at least one additive is selected from the group consisting of a moisturizing agent and an emollient.

98. The method of claim 96, wherein a concentration of said at least one additive ranges between about 1 weight percentage and about 5 weight percentages of the total weight of said composition.

99. The method of claim 96, wherein said at least one additive comprises glycerin.

100. The method of claim 97, wherein said emollient is selected from the group comprising dodecane, squalane, cholesterol, isohexadecane, isononyl isononanoate, PPG Ethers, petrolatum, lanolin, safflower oil, castor oil, coconut oil, cottonseed oil, palm kernel oil, palm oil, peanut oil, soybean oil, polyol carboxylic acid esters, derivatives thereof and mixtures thereof.

101. The method of claim 96, wherein said at least one additive is selected from the group consisting of a humectant, a deodorant agent, all antiperspirant, a stabilizing agent, a pH adjusting agent, a preservative, an emulsifier, an occlusive agent, a solubilizing agent, a colorant, and a surfactant.

128. The method of claim 85, wherein a concentration of said gelling agent ranges between about 0.1 weight percentage and about 5 weight percentages of the total weight of the said composition.

102. A method of treating a medical condition in which elevating a blood serum hormone level in a subject is beneficial, the method comprising:

providing a hydroalcoholic gel pharmaceutical composition for topical application including said hormone, a quaternary ammonium compound, an alcohol and a gelling agent;

topically applying onto at least one biological surface of said subject a pharmaceutically effective amount of said topical pharmaceutical composition, thereby elevating said blood serum hormone level in said subject and treating said medical condition.

103. The method of claim 102, wherein said pharmaceutically effective amount of said hydroalcoholic gel pharmaceutical composition ranges between about 0.1 gram and about 10 grams.

104. The method of claim 102, wherein said amount of said hydroalcoholic gel pharmaceutical composition ranges betweeen about 3 milligrams and about 100 milligrams per square centimeter of said at least one biological surface.

105. The method of claim 104, wherein said amount of said hydroalcoholic gel pharmaceutical composition ranges between about 4 milligrams and about 60 milligrams per square centimeter of said at least one biological surface.

106. The method of claim 102, wherein said hormone level is elevated from a subpotent concentration to a potent concentration within about 24 hours after said topical application.

107. The method of claim 102, wherein said at least one biological surface is selected from the group consisting of the abdomen, an armpit, an inside arm, the back, a thigh, a shoulder, and the scrotum.

108. The method of claim 102, wherein a concentration of said quaternary ammonium compound ranges between about 0.04 weight percentages and about 0.4 weight percentages.

109. The method of claim 108, wherein a concentration of said quaternary ammonium compound ranges between about 0.07 weight percentages and about 0.1 weight percentages.

110. The method of claim 102, wherein said quaternary ammonium compound is selected from the group consisting of benzalkonium chloride, benzethonium chloride, cetrimide, methylbenzethonium chloride, hexadecyltrethylammonium bromide, methylbenzethonium chloride, cetalkonium chloride, centrimonium bromide, domiphen bromide, domiphen chloride, domiphen fluoride, cetyl pyridinium chloride, dequalinium chloride, the cis isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride, cetyl trimethylammonium bromide, benzalkonium saccharinate;

behenalkonium chloride;

cetalkonium chloride;

erucalkonium chloride;

lauralkonium chloride;

myristalkonium chloride;

myristalkonium saccharinate (Quaternium-3);

stearalkonium chloride;

olealkonium chloride;

tallowalkonium chloride;

dodecylbenzyltrimethylammonium chloride (Quaternium-28);

dodecylbenzyl trimethyl ammonium 2-ethylhexanoate;

ethylbenzyl alkyldimethylammonium cyclohexylsulfanamate (Quaternium-8);

ethylbenzyl dimethyl dodecyl ammonium chloride (Quaternium-14);

dodecylbenzyl dimethyl octadecyl ammonium chloride;

dodecylbenzyl triethanol ammonium chloride (Quaternium-30);

benzoxonium chloride;

benzylbis(2-hydroxyethyl)(2-dodecyloxyethyl)ammonium bromide;

benzylbis(2-hydroxyethyl)(2-dodecyloxyethyl)ammonium chloride;

N,N-(dietyl-N-[2-[4-(1,1,3,3-tetramethylbutyl)phenoxy]ethyl] benzenemethanaminium chloride (phenoctide);

dodecarbonium chloride;

babassuamidopropalkonium chloride;

wheatgermamidopropalkonium chloride.

111. The method of claim 110, wherein said quaternary ammonium compound is benzalkonium chloride.

112. The method of claim 102, wherein said hormone is selected from the group consisting of an androgenic hormone, an estrogenic hormone and a progestogenic hormone.

113. The method of claim 112, wherein said hormone is selected from the group consisting of methyltestosterone, androsterone, androsterone acetate, androsterone propionate, androsterone benzoate, androsteronediol, androsteronediol-3-acetate, androsteronediol-17-acetate, androsteronediol 3-17-diacetate, androsteronediol-17-benzoate, androsteronedione, androstenedione, androstenediol, dehydroepiandrosterone, sodium dehydroepiandrosterone sulfate, dromostanolone, dromostanolone propionate, ethylestrenol, fluoxymesterone, nandrolone phenpropionate, nandrolone decanoate, nandrolone furylpropionate, nandrolone cyclohexane-propionate, nandrolone benzoate, nandrolone cyclohexanecarboxylate, androsteronediol-3-acetate-1-7-benzoate, oxandrolone, oxymetholone, stanozolol, testosterone, testosterone decanoate, 4-dihydrotestosterone, 5α

-dihydrotestosterone, testolactone, 17α

-methyl-19-nortestosterone, desogestrel, dydrogesterone, ethynodiol diacetate, medroxyprogesterone, levonorgestrel, medroxyprogesterone acetate, hydroxyprogesterone caproate, norethindrone, norethindrone acetate, norethynodrel, allylestrenol, 19-nortestosterone, lynoestrenol, quingestanol acetate, medrogestone, norgestrienone, dimethisterone, ethisterone, cyproterone acetate, chlormadinone acetate, megestrol acetate, norgestimate, norgestrel, desogrestrel, trimegestone, gestodene, nomegestrol acetate, progesterone, 5α

-pregnan-3β

,20α

-diol sulfate, 5α

-pregnan-3β

,20α

-diol sulfate, 5α

-pregnan-3β

-ol-20-one, 16,5α

-pregnen-3β

-ol-20one, 4-pregnen-20β

-ol-3-one-20-sulfate, acetoxypregnenolone, anagestone acetate, cyproterone, dihydrogesterone, flurogestone acetate, gestadene, hydroxyprogesterone acetate, hydroxymethylprogesterone, hydroxymethyl progesterone acetate, 3-ketodesogestrel, megestrol, melengestrol acetate, norethisterone, estrone, estradiol and estriol, progesterone, pharmaceutically acceptable esters thereof, salts thereof, and combinations of any of the foregoing.

114. The method of claim 113, wherein said hormone is testosterone.

115. The method of claim 102, wherein a concentration of said hormone ranges between about 0.5 weight percentages and about 5 weight percentages of the total weigh of the said composition.

116. The method of claim 115, wherein a concentration of said hormone is about 1 weight percentage of the total weight of the said composition.

117. The method of claim 102, wherein said alcohol is a C2-C4 alcohol.

118. The method of claim 117, wherein said C2-C4 alcohol is selected from the group comprising ethanol and isopropanol.

119. The method of claim 118, wherein said C2-C4 alcohol is ethanol.

120. The method of claim 117, wherein a concentration of said C2-C4 alcohol ranges between about 40 weight percentages and about 90 weight percentages of the total weight of the said composition.

121. The method of claim 120, wherein a concentration of said C2-C4 alcohol ranges between about 55 weight percentages and about 70 weight percentages of the total weight of the said composition.

122. The method of claim 121, wherein a concentration of said C2-C4 alcohol is about 69 weight percentages of the total weight of the said composition.

123. The method of claim 102, wherein said gelling agent is selected from the group consisting of a polymeric thickening agent, a fatty alcohol, a fatty acid, and a fatty acid alkali salt, an inorganic gelling agent and any mixture thereof.

124. The method of claim 102, wherein said gelling agent comprises a polyacrylic acid.

125. The method of claim 123, wherein said polymeric thickening agent comprises a cellulosic ether.

126. The method of claim 125, wherein said cellulosic ether is selected from the group consisting of carboxymethylcellulose, hydroxypropyl cellulose and hydroxyethylcellulose.

127. The method of claim 123, wherein said polymeric thickening agent is selected from the group consisting of xanthan gum and guar gum.

129. The method of claim 102, wherein a concentration of said gelling agent ranges between about 0.1 weight percentage and about 2 weight percentages of the total weight of the said composition.

130. The method of claim 102, wherein said pharmaceutical composition further comprises a penetration co-enhancer.

131. The method of claim 130, wherein said penetration co-enhancer is a glycol.

132. The method of claim 102, wherein said pharmaceutical composition further comprises an additional pharmaceutically active ingredient.

133. The method of claim 102, wherein said pharmaceutical composition further comprises at least one additive.

134. The method of claim 133, wherein said at least one additive is selected from the group consisting of a moisturizing agent and an emollient.

135. The method of claim 133, wherein a concentration of said at least one additive ranges between about 1.0 weight percentages and about 5 weight percentages of the total weight of the said composition.

136. The method of claim 133, wherein said at least one additive comprises glycerin.

137. The method of claim 134, wherein said emollient is selected from the group comprising dodecane, squalane, cholesterol, isohexadecane, isononyl isononanoate, PPG Ethers, petrolatum, lanolin, safflower oil, castor oil, coconut oil, cottonseed oil, palm kernel oil, palm oil, peanut oil, soybean oil, polyol carboxylic acid esters, derivatives thereof and mixtures thereof.

138. The method of claim 133, wherein said at least one additive is selected from the group consisting of a humectant, a deodorant agent an antiperspirant, a stabilizing agent, a stabilizing agent, a pH adjusting agent, a preservative, an emulsifier, an occlusive agent, a solubilizing agent, a colorant, and a surfactant.

139. The method of claim 102, wherein said subject is a human male.

140. The method of claim 139, wherein said medical condition is selected from the group consisting of primary hypogonadism, secondary hypogonadism, age-related hypogonadism, hormone deficiency, erectile dysfunction, AIDS wasting syndrome, reduced sex drive, energy loss, loss of bone mass, extreme tiredness, low energy, and depression.

141. The method of claim 102, wherein said subject is a human female.

142. The method of claim 141, wherein said medical condition is selected from the group consisting of breast cancer, postpartum breast pain or engorgement, reduced sex drive, menopausal symptoms, energy loss, loss of bone mass, extreme tiredness, low energy, and depression.

143. The method of claim 141, wherein said human female is selected from the group consisting of young oophorectomized/hysterectomized women, post-menopausal women on estrogen replacement therapy, women on oral contraceptives, women with adrenal dysfunction, women with corticosteroid-induced adrenal suppression, and human immunodeficiency virus-positive women.

144. The method of claim 102, further comprising co-administering to said subject an additional pharmaceutically active ingredient suitable for treating said medical condition.