Pharmaceutical composition and method for transdermal drug delivery

• US 20050042268A1
• Filed: 07/15/2004
• Published: 02/24/2005
• 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:
  US10/891,489
• Publication Number:
  US 20050042268A1
• Time in Patent Office: Days
• US Class Current: 424/448
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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 47/38 Cellulose; Derivatives thereof
• 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

Abstract

A pharmaceutical composition for transdermal administration of a hormone (e.g., testosterone), which includes urea and/or a derivative thereof 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 pharmaceutical composition for topical application comprising a pharmaceutically active ingredient, a penetration enhancer and a pharmaceutically acceptable carrier, wherein said pharmaceutically active ingredient is a hormone, and said penetration enhancer is urea and/or a derivative thereof.

2. The 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 pharmaceutical composition of claim 2, wherein said amount ranges between about 0-1 grams and about 10 grams.

4. The 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 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 pharmaceutical composition of claim 1, wherein said penetration enhancer is urea.

7. The pharmaceutical composition of claim 1, wherein said urea derivative is selected from the group consisting of urazole and ureaform.

8. The pharmaceutical composition of claim 1, wherein a concentration of said urea and/or said derivative thereof ranges between about 1 weight percentages and about 15 weight percentages.

9. The pharmaceutical composition of claim 8, wherein a concentration of said urea and/or said derivative thereof ranges between about 4 weight percentages and about 10 weight percentages.

10. The pharmaceutical composition of claim 1, having a pH that ranges between about 4 and about 7.

11. The pharmaceutical composition of claim 10, having a pH that ranges between about 4 and about 6.

12. The pharmaceutical composition of claim 11, having a pH of about 4.5.

13. The pharmaceutical composition of claim 10, wherein a concentration of said urea and/or said derivative thereof, ranges between about 1 weight percentages and about 15 weight percentages.

14. The pharmaceutical composition of claim 13, wherein a concentration of said urea and/or said derivative thereof, ranges between about 2.5 weight percentages and about 10 weight percentages.

15. The pharmaceutical composition of claim 1, further comprising at least one substance capable of stabilizing the composition.

16. The pharmaceutical composition of claim 15, wherein said substance is selected from the group consisting of a hydroxyacid, allantoin, a buffer system, an antioxidant, and a mixture thereof.

17. The pharmaceutical composition of claim 16, wherein said hydroxyacid is selected from the group consisting of an alpha hydroxyacid and a beta hydroxyacid.

18. The pharmaceutical composition of claim 17, wherein said hydroxyacid is an alpha hydroxyacid.

19. The pharmaceutical composition of claim 18, wherein said alpha hydroxyacid is lactic acid.

20. The pharmaceutical composition of claim 19, further comprising ammonium hydroxide.

21. The pharmaceutical composition of claim 15, wherein a concentration of said at least one substance ranges between about 0.1 weight percentage and about 15 weight percentages of the total weight of said composition.

22. The pharmaceutical composition of claim 21, wherein a concentration of said at least one substance ranges between about 2 weight percentages and about 7 weight percentages of the total weight of said composition.

23. The pharmaceutical composition of claim 1, wherein said hormone is selected from the group consisting of an androgenic hormone, an esterogenic hormone and a progestogenic hormone.

24. The pharmaceutical composition of claim 23, 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-diaceate, androsteronediol-17-benzoate, androsteronedione, androstenedione, androstenediol, dehydroepiandrosterone, sodium dehydroepiandrosterone sulfate, dromostranolone, 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, desogetrel, dydrogesterone, ethynodiol diacetate, medroxyprogesterone, levonorgesel, medroxyprogesterone acetate, hydroxyprogesterone caproate, norethindrone, norethindrone acetate, norethynodrel, allylestenol, 19-nortestosterone, lynoestrenol, quigestanol acetate, medrogtntne, 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, 4pregnen-20β

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

25. The pharmaceutical composition of claim 24, wherein said hormone is testosterone.

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

27. The pharmaceutical composition of claim 26, wherein a concentration of said hormone is about 1 weight percentage.

28. The pharmaceutical composition of claim 1, being formulated in a form selected from the group consisting of a gel, a cream, an ointment, a paste, a lotion, a milk, a suspension, an aerosol, a spray, a foam, a serum, a swab, a pledget, a pad and a patch.

29. The pharmaceutical composition of claim 28, being formulated as a gel.

30. The pharmaceutical composition of claim 29, wherein said gel is a hydroalcoholic gel.

31. The pharmaceutical composition of claim 30, comprising a C2-C4 alcohol.

32. The pharmaceutical composition of claim 31, wherein said C2-C4 alcohol is selected from the group comprising ethanol and isopropanol.

33. The pharmaceutical composition of claim 32, wherein said C2-C4 alcohol is ethanol.

34. The pharmaceutical composition of claim 31, wherein a concentration of said C2-C4 alcohol ranges between about 40 weight percentages and about 90 weight percentages.

35. The pharmaceutical composition of claim 34, wherein a concentration of said C2-C4 alcohol ranges between about 55 weight percentages and about 70 weight percentages.

36. The pharmaceutical composition of claim 35, wherein a concentration of said C2-C4 alcohol is about 69 weight percentages.

37. The pharmaceutical composition of claim 29, further comprising a gelling agent.

38. The pharmaceutical composition of claim 37, 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.

39. The pharmaceutical composition of claim 37, wherein said gelling agent comprises a polyacrylic acid.

40. The pharmaceutical composition of claim 38, wherein said polymeric thickening agent comprises a cellulosic ether.

41. The pharmaceutical composition of claim 40, wherein said cellulosic ether is selected from the group consisting of carboxymethylcellulose, hydroxypropyl cellulose and hydroxyethylcellulose.

42. The pharmaceutical composition of claim 38, wherein said polymeric thickening agent is selected from the group consisting of xanthan gum and guar gum.

43. The pharmaceutical composition of claim 37, wherein a concentration of said gelling agent ranges between about 0.1 weight percentage and about 5 weight percentages.

44. The pharmaceutical composition of claim 43, wherein a concentration of said gelling agent ranges between about 0.1 weight percentage and about 2 weight percentages.

45. The pharmaceutical composition of claim 1, further comprising a penetration co-enhancer.

46. The pharmaceutical composition of claim 45, wherein said penetration co-enhancer is a glycol.

47. The pharmaceutical composition of claim 1, further comprising an additional pharmaceutically active ingredient.

48. The pharmaceutical composition of claim 1, further comprising at least one additive.

49. The pharmaceutical composition of claim 48, wherein said at least one additive is selected from the group consisting of a moisturizing agent and an emollient.

50. The pharmaceutical composition of claim 48, wherein a concentration of said at least one additive ranges between about 1 weight percentage and about 5 weight percentages.

51. The pharmaceutical composition of claim 48, wherein said at least one additive comprises glycerin.

52. The pharmaceutical composition of claim 49, 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.

53. The pharmaceutical composition of claim 48, wherein said at least one additive is selected from the group consisting of a humectant, a deodorant agent, an antiperspirant, a pH adjusting agent, a preservative, an emulsifier, an occlusive agent a solubilizing agent, a colorant, and a surfactant.

54. The 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 serum hormone level in a subject is beneficial.

55. The pharmaceutical composition of claim 54, wherein said subject is a human male.

56. The pharmaceutical composition of claim 55, 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 dive, energy loss, loss of bone mass, extreme tiredness, low energy, and depression.

57. The pharmaceutical composition of claim 54, wherein said subject is a human female.

58. The pharmaceutical composition of claim 57, 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.

59. The pharmaceutical composition of claim 57, wherein said human female is selected from the group consisting of young oophorectomized/hysterectomized women post-menopausal women on esterogen replacement therapy, women on oral contraceptives, women with adrenal dysfunction, women with corticostroid-induced adrenal suppression, and human immunodeficiency virus-positive women.

60. A hydroalcoholic pharmaceutical composition for topical application comprising testosterone, urea, a C2-C4 alcohol and a gelling agent.

61. The hydroalcoholic pharmaceutical composition of claim 60, 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.

62. The hydroalcoholic pharmaceutical composition of claim 61, wherein said amount ranges between about 0.1 grams and about 10 grams.

63. The hydroalcoholic pharmaceutical composition of claim 60, wherein a concentration of said urea ranges between about 4 weight percentages and about 15 weight percentages.

64. The hydroalcoholic pharmaceutical composition of claim 63, wherein a concentration of said urea ranges between about 4 weight percentages and about 10 weight percentages.

65. The hydroalcoholic pharmaceutical composition of claim 60, having a pH that ranges between about 4 and about 7

66. The hydroalcoholic pharmaceutical composition of claim 65, having a pH that ranges between about 4 and about 6.

67. The hydroalcoholic pharmaceutical composition of claim 66, having a pH of about 4.5.

68. The hydroalcoholic pharmaceutical composition of claim 65, wherein a concentration of said urea ranges between about 1 weight percentages and about 15 weight percentages.

69. The hydroalcoholic pharmaceutical composition of claim 68, wherein a concentration of said urea ranges between about 2.5 weight percentages and about 10 weight percentages.

70. The hydroalcoholic pharmaceutical composition of claim 60, further comprising at least one substance capable of stabilizing the composition.

71. The hydroalcoholic pharmaceutical composition of claim 70, wherein said substance is selected from the group consisting of a hydroxyacid, allantoin, a buffer system, an antioxidant, and a mixture thereof.

72. The hydroalcoholic pharmaceutical composition of claim 71, wherein said hydroxyacid is selected from the group consisting of an alpha hydroxyacid and a beta hydroxyacid.

73. The hydroalcoholic pharmaceutical composition of claim 72, wherein said hydroxyacid is an alpha hydroxyacid.

74. The hydroalcoholic pharmaceutical composition of claim 73, wherein said alpha hydroxyacid is lactic acid.

75. The hydroalcoholic pharmaceutical composition of claim 74, further comprising ammonium hydroxide.

76. The hydroalcoholic pharmaceutical composition of claim 70, wherein a concentration of said at least one substance ranges between about 0.1 weight percentage and about 15 weight percentages.

77. The hydroalcoholic pharmaceutical composition of claim 76, wherein a concentration of said at least one substance ranges between about 2 weight percentages and about 7 weight percentages.

78. The hydroalcoholic pharmaceutical composition of claim 60, wherein a concentration of said testosterone ranges between about 0.5 and about 5 weight percentages.

79. The hydroalcoholic pharmaceutical composition of claim 78, wherein a concentration of said testosterone is about 1 weight percentage.

80. The hydroalcoholic pharmaceutical composition of claim 60, further comprising an additional pharmaceutically active ingredient.

81. The hydroalcoholic pharmaceutical composition of claim 60, 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.

82. The hydroalcoholic pharmaceutical composition of claim 81, wherein said subject is a human male.

83. The hydroalcoholic pharmaceutical composition of claim 82, 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.

84. The hydroalcoholic, pharmaceutical composition of claim 82, 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.

85. The hydroalcoholic pharmaceutical composition of claim 81, wherein said subject is a human female.

86. The hydroalcoholic pharmaceutical composition of claim 85, 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.

87. The hydroalcoholic pharmaceutical composition of claim 85, wherein said human female is selected from the group consisting of young oophorectomized/hysterectomized women, post-menopausal women on esterogen replacement therapy, women on oral contraceptives, women with adrenal dysfunction, women with corticosteroid-induced adrenal suppression, and human immunodeficiency virus-positive women.

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

providing a pharmaceutical composition for topical application including said hormone, urea and/or a derivative thereof, and a pharmaceutically acceptable carrier; 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.

89. The method of claim 88, wherein said amount of said pharmaceutical composition ranges between about 0.1 gram and about 10 grams.

90. The method of claim 88, wherein said amount of said pharmaceutical composition ranges between about 3 milligrams and about 100 milligrams per square centimeter of said at least one biological surface.

91. The method of claim 88, wherein said amount ranges between about 4 milligrams and about 60 milligrams per square centimeter of said at least one biological surface.

92. The method of claim 88, 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.

93. The method of claim 88, 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.

94. The method of claim 88, wherein said composition includes urea.

95. The method of claim 88, wherein said urea derivative is selected from the group consisting of urazole and ureaform.

96. The method of claim 88, wherein a concentration of said urea and/or said derivative thereof ranges between about 4 weight percentage and about 15 weight percentages of the total weight of said composition.

97. The hydroalcoholic pharmaceutical composition of claim 96, wherein a concentration of said urea ranges between about 4 weight percentages and about 10 weight percentages.

98. The method of claim 88, wherein said pharmaceutical composition has a pH that ranges between about 4 and about 7.

99. The method of claim 98, wherein said pharmaceutical composition has a pH that ranges between about 4 and about 6.

100. The method of claim 99, wherein said pharmaceutical composition has a pH of about 4.5.

101. The method of claim 98, wherein a concentration of said urea and/or said derivative thereof, ranges between about 1 weight percentage and about 15 weight percentages of the total weight of said composition.

102. The method of claim 98, wherein a concentration of said urea and/or said derivative thereof ranges between about 2.5 weight percentage and about 10 weight percentages of the total weight of said composition.

103. The method of claim 88, wherein said pharmaceutical composition further comprises at least one substance capable of stabilizing said composition.

104. The method of claim 103, wherein said substance is selected from the group consisting of a hydroxyacid, allantoin, a buffer system, an antioxidant, and a mixture thereof.

105. The method of claim 104, wherein said hydroxyacid is selected from the group consisting of an alpha hydroxyacid and a beta hydroxyacid.

106. The method of claim 105, wherein said hydroxyacid is an alpha hydroxyacid.

107. The method of claim 106, wherein said alpha hydroxyacid is lactic acid.

108. The method of claim 107, wherein said pharmaceutical composition further comprises ammonium hydroxide.

109. The method of claim 103, wherein a concentration of said at least one substance ranges between about 0.1 weight percentage and about 15 weight percentages of the total weight of said composition.

110. The method of claim 109, wherein a concentration of said at least one substance ranges between about 2 weight percentages and about 7 weight percentages of the total weight of said composition.

111. The method of claim 88, wherein said hormone is selected from the group consisting of an androgenic hormone, an esterogenic hormone and a progestogenic hormone.

112. The method of claim 111, 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, ehylestrenol, fluoxyrnerterone, nandrolone phenpropionate, nandrolone decanoate, nadrolone 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-norteitosterone, desogestrel, dydrogesterone, ethynodiol diacetate, medroxyprogesteroae, levonorgestrel, medroxyprogesterone acetate, hydroxyprogesternc caproate, norethindrone, norethidrone acetate, noretynodrel, allylestrenol, 19-nortestosterone, lynoestrenol, quingestanol acetate, medrogestone, norgestrienone, dimethisterone, ethisterone, cyproterone acetate, chlormadinone acetate, inegestrol acetate, norgestimate, norgestrel, desogrestrel, triregestone, 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, megesrol, melengestrol acetate, norethisterone, esterone, estradiol and estriol, progesterone, pharmaceutically acceptable esters, salts thereof, and combinations of any of the foregoing.

113. The method of claim 112, wherein said hormone is testosterone.

114. The method of claim 88, 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.

115. The method of claim 114, wherein a concentration of said hormone is about 1 weight percentage of the total weight of said composition.

116. The method of claim 88, wherein said pharmaceutical composition is formulated in a form selected from the group consisting of a gel, a cream, an ointment, a paste, a lotion, a milk, a suspension, an aerosol, a spray, a foam, a serum, a swab, a pledget, a pad and a patch.

117. The method of claim 116, wherein said pharmaceutical composition is formulated as a gel.

118. The method of claim 117, wherein said gel is a hydroalcoholic gel.

119. The method of claim 118, wherein said hydroalcoholic gel comprises a C2-C4 alcohol.

120. The method of claim 119, wherein said C2-C4 alcohol is selected from the group comprising ethanol and isopropanol.

121. The method of claim 120, where said C2-C4 alcohol is ethanol.

122. The method of claim 120, 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.

123. The method of claim 122, 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.

124. The method of claim 123, wherein a concentration of said C2-C4 alcohol is about 69 weight percentages of the total weight of said composition.

125. The method of claim 117, wherein said pharmaceutical composition further comprises a gelling agent.

126. The method of claim 125, 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.

127. The method of claim 125, wherein said gelling agent comprises a polyacrylic acid.

128. The method of claim 126, wherein said polymeric thickening agent comprises a cellulosic ether.

129. The method of claim 128, wherein said cellulosic ether is selected from the group consisting of carboxymethylcellulose, hydroxypropyl cellulose and hydroxyethylcellulose.

130. The method of claim 126, wherein said polymeric thickening agent is selected from the group consisting of xanthan gum and guar gum.

131. The method of claim 126, 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.

132. The method of claim 131, 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.

133. The method of claim 88, wherein said pharmaceutical composition further comprises a penetration co-enhancer.

134. The method of claim 133, wherein said penetration co-enhancer is a glycol.

135. The method of claim 88, wherein said pharmaceutical composition further comprises an additional pharmaceutically active ingredient.

136. The method of claim 88, wherein said pharmaceutical composition further comprises at least one additive.

137. The method of claim 136, wherein said at least one additive is selected from the group consisting of a moisturizing agent and an emollient.

138. The method of claim 136, 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.

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

140. The method of claim 137, 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.

141. The method of claim 136, wherein said at least one additive is selected from the group consisting of a humectant, a deodorant agent, an antiperspirant, a pH adjusting agent, a preservative, an emulsifier, an occlusive agent, a solubilizing agent, a colorant, and a surfactant.

142. 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 pharmaceutical composition for topical application including said hormone, urea and/or a derivative thereof and a pharmaceutically acceptable carrier;

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.

143. The method of claim 142, wherein said pharmaceutically effective amount of said pharmaceutical composition ranges between about 0.1 gram and about 10 grams.

144. The method of claim 142, wherein said amount of said pharmaceutical composition ranges between about 3 milligrams and about 100 milligrams per square centimeter of said at least one biological surface.

145. The method of claim 144, wherein said amount of said pharmaceutical composition ranges between about 4 milligrams arid about 60 milligrams per square centimeter of said at least one biological surface.

146. The method of claim 142, wherein said hormone level is elevated form a subpotent concentration to a potent concentration within about 24 hours after said topical application.

147. The method of claim 142, 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.

148. The method of claim 142, wherein said composition includes urea.

149. The method of claim 142, wherein said urea derivative is selected from the group consisting of urazole and ureaform.

150. The method of claim 142, wherein a concentration of said urea and/or said derivative thereof ranges between about 1 weight percentages and about 15 weight percentages of the total weight of said composition.

151. The method of claim 142, wherein a concentration of said urea and/or said derivative thereof ranges between about 4 weight percentages and about 10 weight percentages of the total weight of said composition.

152. The method of claim 142, wherein said pharmaceutical composition has a pH that ranges between about 4 and about 7.

153. The method of claim 152, wherein said pharmaceutical composition has a pH that ranges between about 4 and about 6.

154. The method of claim 153, wherein said pharmaceutical composition has a pH of about 4.5.

155. The method of claim 152, wherein a concentration of said urea and/or said derivative thereof, ranges between about 1 weight percentages and about 15 weight percentages of the total weight of said composition.

156. The method of claim 152, wherein a concentration of said urea and/or said derivative thereof, ranges between about 2.5 weight percentages and about 10 weight percentages of the total weight of said composition.

157. The method of claim 142, wherein said pharmaceutical composition further comprises at eat one substance capable of stabilizing the composition.

158. The method of claim 157, wherein said substance is selected from the group consisting of a hydroxyacid, allantoin, a buffer system, an antioxidant, and a mixture thereof.

159. The method of claim 158, wherein said hydroxyacid is selected from the group consisting of an alpha hydroxyacid and a beta hydroxyacid.

160. The method of claim 159, wherein said hydroxyacid is an alpha hydroxyacid.

161. The method of claim 160, wherein said alpha hydroxyacid is lactic acid.

162. The method of claim 161, wherein said pharmaceutical composition further comprises ammonium hydroxide.

163. The method of claim 157, wherein a concentration of said at least one substance ranges between about 0.1 weight percentage and about 15 weight percentages of the total weight of said composition.

164. The method of claim 163, a concentration of said at least one substance ranges between about 2 weight percentage and about 7 weight percentages of the total weight of said composition.

165. The method of claim 142, wherein said hormone is selected from the group consisting of an androgenic hormone, an esterogenic hormone and a progestogenic hormone.

166. The method of claim 165, 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 dehydrocpiandrosterone sulfate, dromostanolone, dromostanolone propionate, ethylestrenol, fluoxyraesterone, 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, norgesitiate, 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

-pregen-3β

-ol-20-one, 4-pregnen-20β

-ol-3-one-20-sulfate, acetoxypregaenolone, anagestone acetate, cyprotcronc, dihydrogesterone, flurogestone acetate, gestadene, hydroxyprogesterone acetate, hydroxynethylprogesterone, hydroxymethyl progesterone acetate, 3-ketodesogestrol, megestrol, melengestrol acetate, norethisteone, esterone, esteradiol and estriol, progesterone, pharmaceutically acceptable esters thereof, salts thereof, and combinations of any of the foregoing.

167. The method of claim 166, wherein said hormone is testosterone.

168. The method of claim 142, 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.

169. The method of claim 168, wherein a concentration of said hormone is about 1 weight percentage of the total weight of the composition.

170. The method of claim 142, wherein said pharmaceutical composition is formulated in a form selected from the group consisting of a gel, a cream, an ointment, a paste, a lotion, a milk, a suspension, an aerosol, a spray, a foam, a serum, a swab, a pledget a pad and a patch.

171. The method of claim 170, wherein said pharmaceutical composition is formulated as a gel.

172. The method of claim 171, wherein sad gel is a hydroalcoholic gel.

173. The method of claim 172, wherein said hydroalcoholic gel comprises a C2-C4 alcohol.

174. The method of claim 173, wherein said C2-C4 alcohol is selected from the group comprising ethanol and isopropanol.

175. The method of claim 174, wherein said C2-C4 alcohol is ethanol.

176. The method of claim 173, 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.

177. The method of claim 176, 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.

178. The method of claim 177, wherein a concentration of said C2-C4 alcohol is about 69 weight percentages of the total weight of the said composition.

179. The method of claim 142, wherein said pharmaceutical composition further comprises a gelling agent.

180. The method of claim 179, 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.

181. The method of claim 179, wherein said gelling agent comprises a polyacrylic acid.

182. The method of claim 180, wherein said polymeric thickening agent comprises a cellulosic ether.

183. The method of claim 182, wherein said cellulosic ether is selected from the group consisting of carboxymethylcellulose, hydroxypropyl cellulose and hydroxyethylcellulose.

184. The method of claim 180, wherein said polymeric thickening agent is selected from the group consisting of xanthan gum and guar gum.

185. The method of claim 180, 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.

186. The method of claim 185, wherein a concentration of said getting agent ranges between about 0.1 weight percentage and about 2 weight percentages of the total weight of the said composition.

187. The method of claim 142, wherein said pharmaceutical composition further comprises a penetration co-enhancer.

188. The method of claim 187, wherein said penetration co-enhancer is a glycol.

189. The method of claim 142, wherein said pharmaceutical composition further comprises an additional pharmaceutically active ingredient.

190. The method of claim 142, wherein said pharmaceutical composition further comprises at least one additive.

191. The method of claim 190, wherein said at least one additive is selected from the group consisting of a moisturizing agent and an emollient.

192. The method of claim 190, 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.

193. The method of claim 190, wherein said at least one additive comprises glycerin.

194. The method of claim 191, 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.

195. The method of claim 190, wherein said at least one additive is selected from the group consisting of a humectant, a deodorant agent, an antiperspirant, a pH adjusting agent, a preservative, an emulsifier, an occlusive agent, a solubilizing agent, a colorant, and a surfactant.

196. The method of claim 142, wherein said subject is a human male.

197. The method of claim 196, 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.

198. The method of claim 142, wherein said subject is a human female.

199. The method of claim 198, 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.

200. The method of claim 198, wherein said human female is selected from the group consisting of young oophorectomized/hysterectomized women, post-menopausal women on esterogen replacement therapy, women on oral contraceptives, women with adrenal dysfunction, women with corticosteroid-induced adrenal suppression, and human immunodeficiency virus-positive women.

201. The method of claim 142, further comprising co-administering to said subject an additional pharmaceutically active ingredient suitable for treating said medical condition.