Physical and chemical properties of thyroid hormone organic acid addition salts

• US 7,858,663 B1
• Filed: 10/31/2007
• Issued: 12/28/2010
• Est. Priority Date: 10/31/2007
• Status: Active Grant

• Current Assignee: Pisgah Labs, Inc. (IPCA Laboratories Limited), Pisgah Laboratories, Inc.
• Original Assignee: Pisgah Laboratories, Inc.
• Inventors: Audia, Vicki Haynes, King, Clifford Riley, Bristol, David William
• Primary Examiner(s): Henley, III; Raymond J
• Application Number:
  US11/932,336
• Time in Patent Office: 1,154 Days
• Field of Search: 514/561
• US Class Current: 514/561
• 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 31/195 having an amino group
• CPC Class Codes: A61K 38/24 Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

A pharmaceutical composition comprising the salt of a thyroid hormone selected from the group consisting of levothyroxine and liothyronine and an organic acid comprising at least one aromatic ring having at least one hydroxyl moiety and at least one carboxylic acid moiety in an ortho relationship.

Claims

1. A pharmaceutical composition comprising the salt of a thyroid hormone selected from the group consisting of levothyroxine and liothyronine and an organic acid comprising at least one aromatic ring having at least one hydroxyl moiety and at least one carboxylic acid moiety in an ortho relationship.

2. The pharmaceutical composition of claim 1 wherein said organic acid is defined as

3. The pharmaceutical composition of claim 2 wherein said organic acid is defined as

4. The pharmaceutical composition of claim 2 wherein said organic acid is defined as

5. The pharmaceutical composition of claim 2 wherein said organic acid is defined as

6. The pharmaceutical composition of claim 2 wherein said organic acid is defined as

7. The pharmaceutical composition of claim 2 wherein said organic acid is defined as

8. The pharmaceutical composition of claim 2 wherein said organic acid is defined as

9. The pharmaceutical composition of claim 1 wherein said organic acid is selected from the group consisting of pamoic acid, disodium pamoate, di-ammonium pamoate, di-potassium pamoate, di-alkyl and/or di-aryl amine pamoate, di-alkyl and/or di-aryl esters of pamoic acid, and di-alkylacyl and/or di-arylacyl O-esters of pamoic acid.

10. The pharmaceutical composition of claim 9 wherein said organic acid is selected from the group consisting of pamoic acid and disodium pamoate.

11. The pharmaceutical composition of claim 1 wherein said thyroid hormone and said organic acid are in a stoichiometric ratio of 1:

1 to 2;

1.

12. The pharmaceutical composition of claim 1 wherein said thyroid hormone and said organic acid are in a stoichiometric ratio of 1:

1.

13. The pharmaceutical composition of claim 1 wherein said thyroid hormone and said organic acid are in a stoichiometric ratio of 2:

1.

14. The pharmaceutical composition of claim 1 comprising 25-300 μ

g of said thyroid hormone per unit dose.

15. The pharmaceutical composition of claim 1 in a form selected from a pill, a tablet, a capsule, a solution, a suspension injection dose, a transdermal patch and an inhalation formulation.

16. A drug product comprising said pharmaceutical composition of claim 1.

17. The pharmaceutical composition of claim 1 further comprising at least one additive selected from an excipient, a processing aid and a buffer.

18. The pharmaceutical composition of claim 1 wherein said salt comprises liothyronine pamoate with a differential scanning calorimetry thermogram of FIG. 1.

19. The pharmaceutical composition of claim 1 wherein said salt comprises liothyronine pamoate with a Fourier Transform Infrared spectrum of FIG. 2.

20. The pharmaceutical composition of claim 1 wherein said salt comprises liothyronine pamoate with a Powder X-Ray Diffraction diffractogram of FIG. 3.

21. The pharmaceutical composition of claim 1 wherein said salt comprises liothyronine pamoate with a proton nuclear magnetic resonance spectrum of FIG. 4.

22. The pharmaceutical composition of claim 1 wherein said salt comprises liothyronine pamoate with a high pressure liquid chromatograph chromatogram of FIG. 5.

23. The pharmaceutical composition of claim 1 wherein said comprises levothyroxine pamoate with a differential scanning calorimetry thermogram of FIG. 9.

24. The pharmaceutical composition of claim 1 wherein said salt comprises levothyroxine pamoate with a Fourier Transform Infrared spectrum of FIG. 10.

25. The pharmaceutical composition of claim 1 wherein said salt comprises levothyroxine pamoate with a Powder X-Ray Diffraction diffractogram of FIG. 11.

26. The pharmaceutical composition of claim 1 wherein said salt comprises levothyroxine pamoate with a proton nuclear magnetic resonance spectrum of FIG. 12.

27. The pharmaceutical composition of claim 1 wherein said salt comprises levothyroxine pamoate with an HPLC chromatogram of FIG. 13.

28. The pharmaceutical composition of claim 1 wherein said salt of a thyroid hormone is selected from the group consisting of levothyroxine pamoate and liothyronine pamoate.

29. A method of administering a thyroid hormone comprising:

forming a drug substance comprising a salt of a thyroid hormone selected from the group consisting of levothyroxine and liothyronine and an organic acid comprising at least one aromatic ring having at least one hydroxyl moiety and at least one carboxylic acid moiety in an ortho relationship;

incorporating said drug substance into a drug product wherein said drug product has 25-300 μ

g of said thyroid hormone and a molar ratio of said thyroid hormone to said organic acid of at least 0.9;

1 to no more than 2.1;

1; and

administering said drug product to a patient.

35. The method of administering a thyroid hormone of claim 29 wherein said organic acid is defined as

36. The method of administering a thyroid hormone of claim 35 wherein said organic acid is defined as

37. The method of administering a thyroid hormone of claim 35 wherein said organic acid is defined as

38. The method of administering a thyroid hormone of claim 35 wherein said organic acid is defined as

39. The method of administering a thyroid hormone of claim 35 wherein said organic acid is defined as

40. The method of administering a thyroid hormone of claim 35 wherein said organic acid is defined as

41. The method of administering a thyroid hormone of claim 35 wherein said organic acid is defined as

42. The method of administering a thyroid hormone of claim 29 wherein said organic acid is selected from the group consisting of pamoic acid, disodium pamoate, di-ammonium pamoate, di-potassium pamoate, di-alkyl and/or di-aryl amine pamoate, di-alkyl and/or di-aryl esters of pamoic acid, and di-alkylacyl and/or di-arylacyl O-esters of pamoic acid.

43. The method of administering a thyroid hormone of claim 42 wherein said organic acid is selected from the group consisting of pamoic acid and disodium pamoate.

44. The method of administering a thyroid hormone of claim 29 wherein said drug product is an oral dose.

45. The method of administering a thyroid hormone of claim 29 wherein said drug product is in a form selected from a pill, a tablet, a capsule a solution, a suspension injection dose, a transdermal patch and an inhalation formulation.

46. The method of administering a thyroid hormone of claim 29 wherein said drug product further comprises at least one additive selected from an excipient, a processing aid and a buffer.

47. The method of administering a thyroid hormone of claim 29 wherein said salt of a thyroid hormone is selected from the group consisting of levothyroxine pamoate and liothyronine pamoate.

48. The method of administering a thyroid hormone of claim 29 wherein said thyroid hormone is administered for treatment of at least one disease selected from hypothyroidism;

cretinism, myxedema, nontoxic goiter, nonendemic goiter, chronic lymphocytic thyroiditis, and thyroid cancer.

30. A method of manufacturing a stable drug substance as a thyroid treatment comprising:

combining a thyroid hormone with a predetermined first stoichiometric ratio of an organic acid comprising at least one aromatic ring having at least one hydroxyl moiety and at least one carboxylic acid moiety in an ortho relationship thereby forming a thyroid hormone salt;

storing said thyroid hormone salt for a predetermined time thereby forming an aged drug substance; and

determining a second stoichiometric ratio of said thyroid hormone and said organic acid in said aged drug substance.

49. The method of manufacturing a stable drug substance of claim 30 comprising determining said second stoichiometric ratio by a chromatographic technique.

50. The method of manufacturing a stable drug substance of claim 30 wherein said predetermined time is at least 1 year.

51. The method of manufacturing a stable drug substance of claim 30 wherein said predetermined time is at least 2 years.

52. The method of manufacturing a stable drug substance of claim 51 wherein said predetermined time is at least 4 years.

53. The method of manufacturing a stable drug substance of claim 30 wherein said storing is under accelerated aging conditions comprising at least one perturbation from ambient selected from temperature above ambient, temperature below ambient, light exposure, solvent exposure, pH alterations, oxidative conditions and exposure to an atmosphere which differs from air.

54. The method of manufacturing a stable drug substance of claim 53 wherein said storing is at ambient conditions.

55. The method of manufacturing a stable drug substance of claim 54 wherein said second stoichiometric ratio is at least 95% to no more than 105% of said first stoichiometric ratio.

56. The method of manufacturing a stable drug substance of claim 55 wherein said second stoichiometric ratio is at least 98% to no more than 102% of said first stoichiometric ratio.

57. The method of manufacturing a stable drug substance of claim 56 wherein said second stoichiometric ratio is at least 99% to no more than 101% of said first stoichiometric ratio.

58. The method of manufacturing a stable drug substance of claim 30 wherein said drug product is a solid oral dose.

59. The method of manufacturing a stable drug substance of claim 30 wherein said organic acid is defined as

60. The method of manufacturing a stable drug substance of claim 59 wherein said organic acid is defined as

61. The method of manufacturing a stable drug substance of claim 59 wherein said organic acid is defined as

62. The method of manufacturing a stable drug substance of claim 59 wherein said organic acid is defined as

63. The method of manufacturing a stable drug substance of claim 59 wherein said organic acid is defined as

64. The method of manufacturing a stable drug substance of claim 59 wherein said organic acid is defined as

65. The method of manufacturing a stable drug substance of claim 59 wherein said organic acid is defined as

66. The method of manufacturing a stable drug substance of claim 30 wherein said organic acid is selected from the group consisting of pamoic acid, disodium pamoate, di-ammonium pamoate, di-potassium pamoate, di-alkyl and/or di-aryl amine pamoate, di-alkyl and/or di-aryl esters of pamoic acid, and di-alkylacyl and/or di-arylacyl O-esters of pamoic acid.

67. The method of manufacturing a stable drug substance of claim 66 wherein said organic acid salt is selected from the group consisting of pamoic acid and disodium pamoate.

68. The method of manufacturing a stable drug substance of claim 30 wherein said thyroid hormone and said organic acid are in a stoichiometric ratio of 1:

1 to 2;

1.

69. The method of manufacturing a stable drug substance of claim 30 wherein said thyroid hormone and said organic acid are in a stoichiometric ratio of 1:

1.

70. The method of manufacturing a stable drug substance of claim 30 wherein said thyroid hormone and said organic acid are in a stoichiometric ratio of 2:

1.

71. The method of manufacturing a stable drug substance of claim 30 wherein said drug substance comprises 25-300 μ

g of said thyroid hormone.

72. The method of manufacturing a stable drug substance of claim 30 wherein said drug substance is incorporated into a drug product in a form selected from a pill, a tablet, a capsule, a solution, a suspension injection dose, a transdermal patch and an inhalation formulation.

73. The method of manufacturing a stable drug substance of claim 30 further comprising adding at least one additive selected from an excipient, a processing aid and a buffer.

74. The method of manufacturing a stable drug substance of claim 30 wherein said salt comprises liothyronine pamoate with a differential scanning calorimetry thermogram of FIG. 1.

75. The method of manufacturing a stable drug substance of claim 30 wherein said salt comprises liothyronine pamoate with a Fourier Transform Infrared spectrum of FIG. 2.

76. The method of manufacturing a stable drug substance of claim 30 wherein said salt comprises liothyronine pamoate with a Powder X-Ray Diffraction diffractogram of FIG. 3.

77. The method of manufacturing a stable drug substance of claim 30 wherein said salt comprises liothyronine pamoate with a proton nuclear magnetic resonance spectrum of FIG. 4.

78. The method of manufacturing a stable drug substance of claim 30 wherein said salt comprises liothyronine pamoate with a high pressure liquid chromatograph chromatogram of FIG. 5.

79. The method of manufacturing a stable drug substance of claim 30 wherein said comprises levothyroxine pamoate with a differential scanning calorimetry thermogram of FIG. 9.

80. The method of manufacturing a stable drug substance of claim 30 wherein said salt comprises levothyroxine pamoate with a Fourier Transform Infrared spectrum of FIG. 10.

81. The method of manufacturing a stable drug substance of claim 30 wherein said salt comprises levothyroxine pamoate with a Powder X-Ray Diffraction diffractogram of FIG. 11.

82. The method of manufacturing a stable drug substance of claim 30 wherein said salt comprises levothyroxine pamoate with a proton nuclear magnetic resonance spectrum of FIG. 12.

83. The method of manufacturing a stable drug substance of claim 30 wherein said salt comprises levothyroxine pamoate with an HPLC chromatogram of FIG. 13.

84. The method of manufacturing a stable drug substance of claim 30 wherein said salt of a thyroid hormone is selected from the group consisting of levothyroxine pamoate and liothyronine pamoate.

31. A method of manufacturing a drug product as a thyroid treatment comprising:

combining a thyroid hormone with a predetermined first stoichiometric ratio of organic acid comprising at least one aromatic ring having at least one hydroxyl moiety and at least one carboxylic acid moiety, both in an ortho or vicinal relationship thereby forming a thyroid hormone salt;

forming a drug product comprising said thyroid hormone salt;

storing said drug product for a predetermined time thereby forming an aged drug product; and

determining a second stoichiometric ratio of said thyroid hormone and said organic acid salt in said aged drug product.

85. The method of manufacturing a drug product of claim 31 wherein said predetermined time is at least 1 year.

86. The method of manufacturing a drug product of claim 85 wherein said predetermined time is at least 2 years.

87. The method of manufacturing a drug product of claim 86 wherein said predetermined time is 4 years.

88. The method of manufacturing a drug product of claim 31 wherein said storing is under accelerated aging conditions comprising at least one perturbation from ambient selected from temperature above ambient, temperature below ambient, light exposure, solvent exposure, pH alterations, oxidative conditions and exposure to an atmosphere which differs from air.

89. The method of manufacturing a drug product of claim 85 wherein said storing is at ambient conditions.

90. The method of manufacturing a drug product of claim 89 wherein said second stoichiometric ratio is at least 95% to no more than 105% of said first stoichiometric ratio.

91. The method of manufacturing a drug product of claim 90 wherein said second stoichiometric ratio is at least 98% to no more than 102% of said first stoichiometric ratio.

92. The method of manufacturing a drug product of claim 91 wherein said second stoichiometric ratio is at least 99% to no more than 101% of said first stoichiometric ratio.

93. The method of manufacturing a drug product of claim 31 wherein said drug product is a solid oral dose.

94. The method of manufacturing a drug product of claim 31 wherein said organic acid is defined as

95. The method of manufacturing a drug product of claim 94 wherein said organic acid is defined as

96. The method of manufacturing a drug product of claim 94 wherein said organic acid is defined as

97. The method of manufacturing a drug product of claim 94 wherein said organic acid is defined as

98. The method of manufacturing a drug product of claim 94 wherein said organic acid is defined as

99. The method of manufacturing a drug product of claim 94 wherein said organic acid is defined as

100. The method of manufacturing a drug product of claim 94 wherein said organic acid is defined as

101. The method of manufacturing a drug product of claim 31 wherein said organic acid is selected from the group consisting of pamoic acid, disodium pamoate, di-ammonium pamoate, di-potassium pamoate, di-alkyl and/or di-aryl amine pamoate, di-alkyl and/or di-aryl esters of pamoic acid, and Idi-alkylacyl and/or di-arylacyl O-esters of pamoic acid.

102. The method of manufacturing a drug product of claim 31 wherein said organic acid salt is selected from the group consisting of pamoic acid and disodium pamoate.

103. The method of manufacturing a drug product of claim 31 wherein said thyroid hormone salt and said organic acid are in a stoichiometric ratio of 1:

1 to 2;

1.

104. The method of manufacturing a drug product of claim 31 wherein said thyroid hormone and said organic acid are in a stoichiometric ratio of 1:

1.

105. The method of manufacturing a drug product of claim 31 wherein said thyroid hormone and said organic acid are in a stoichiometric ratio of 2:

1.

106. The method of manufacturing a drug product of claim 31 wherein said organic acid salt comprising 25-300 μ

g of said thyroid hormone.

107. The method of manufacturing a drug product of claim 31 wherein said drug substance is incorporated into a drug product in a form selected from a pill, a tablet, a capsule, a solution, a suspension injection dose, a transdermal patch and an inhalation formulation.

108. The method of manufacturing a drug product of claim 31 further comprising adding at least one additive selected from an excipient, a processing aid and a buffer.

109. The method of manufacturing a drug product of claim 31 wherein said salt comprises liothyronine pamoate with a differential scanning calorimetry thermogram of FIG. 1.

110. The method of manufacturing a drug product of claim 31 wherein said salt comprises liothyronine pamoate with a Fourier Transform Infrared spectrum of FIG. 2.

111. The method of manufacturing a drug product of claim 31 wherein said salt comprises liothyronine pamoate with a Powder X-Ray Diffraction diffractogram of FIG. 3.

112. The method of manufacturing a drug product of claim 31 wherein said salt comprises liothyronine pamoate with a proton nuclear magnetic resonance spectrum of FIG. 4.

113. The method of manufacturing a drug product of claim 31 wherein said salt comprises liothyronine pamoate with a high pressure liquid chromatograph chromatogram of FIG. 5.

114. The method of manufacturing a drug product of claim 31 wherein said salt comprises levothyroxine pamoate with a differential scanning calorimetry thermogram of FIG. 9.

115. The method of manufacturing a drug product of claim 31 wherein said salt comprises levothyroxine pamoate with a Fourier Transform Infrared spectrum of FIG. 10.

116. The method of manufacturing a drug product of claim 31 wherein said salt comprises levothyroxine pamoate with a Powder X-Ray Diffraction diffractogram of FIG. 11.

117. The method of manufacturing a drug product of claim 31 wherein said salt comprises levothyroxine pamoate with a proton nuclear magnetic resonance spectrum of FIG. 12.

118. The method of manufacturing a drug product of claim 31 wherein said salt comprises levothyroxine pamoate with an HPLC chromatogram of FIG. 13.

119. The method of manufacturing a drug product of claim 31 wherein said salt of a thyroid hormone is selected from the group consisting of levothyroxine pamoate and liothyronine pamoate.

32. A process for the preparation of an organic acid salt of a thyroid hormone comprising the steps of:

a) preparing a first mixture comprising an alkali earth salt, free base or mineral acid salt of said thyroid hormone;

b) preparing an organic acid mixture wherein said organic acid comprises at least one aromatic ring substituted with at least one hydroxyl group and at least one carboxyl group in an ortho relationship to one another,

c) combining said first mixture and said organic acid mixture wherein said thyroid hormone and said aromatic acid form said organic acid salt of a thyroid hormone;

d) isolating said organic acid salt of a thyroid hormone by at least one method selected from filtration, centrifugation and solvent evaporation; and

e) purifying said organic acid salt of a thyroid hormone by at least one method selected from recrystallization, digestion and chromatographic separation.

120. The process for the preparation of an organic acid salt of a thyroid hormone of claim 32 wherein said thyroid hormone is selected from the group consisting of levothyroxine and liothyronine.

121. The process for the preparation of an organic acid salt of a thyroid hormone of claim 32 wherein said organic acid is defined as

122. The process for the preparation of an organic acid salt of a thyroid hormone of claim 121 wherein said organic acid is defined as

123. The process for the preparation of an organic acid salt of a thyroid hormone of claim 121 wherein said organic acid is defined as

124. The process for the preparation of an organic acid salt of a thyroid hormone of claim 121 wherein said organic acid is defined as

125. The process for the preparation of an organic acid salt of a thyroid hormone of claim 121 wherein said organic acid is defined as

126. The process for the preparation of an organic acid salt of a thyroid hormone of claim 121 wherein said organic acid is defined as

127. The process for the preparation of an organic acid salt of a thyroid hormone of claim 121 wherein said organic acid is defined as

128. The process for the preparation of an organic acid salt of a thyroid hormone of claim 32 wherein said organic acid is selected from the group consisting of pamoic acid, disodium pamoate, di-ammonium pamoate, di-potassium pamoate, di-alkyl and/or di-aryl amine pamoate, di-alkyl and/or di-aryl esters of pamoic acid, and di-alkylacyl and/or di-arylacyl O-esters of pamoic acid, i.e. those alkylacyl and arylacyl esters formed using the hydroxyl moiety of pamoic acid and not the carboxylic acid functional group.

129. The process for the preparation of an organic acid salt of a thyroid hormone of claim 32 wherein said organic acid is selected from the group consisting of pamoic acid and disodium pamoate.

130. The process for the preparation of an organic acid salt of a thyroid hormone of claim 32 wherein at least one of said first solution and said organic acid solution comprises water.

131. The process for the preparation of an organic acid salt of a thyroid hormone of claim 130 wherein at least one of said first solution and said organic acid solution is at a pH between 1.5 and 13.

132. The process for the preparation of an organic acid salt of a thyroid hormone of claim 32 wherein said thyroid hormone and said organic acid are in a stoichiometric ratio of at least 0.9:

1 to no more than 2.1;

1.

133. The process for the preparation of an organic acid salt of a thyroid hormone of claim 32 wherein said organic acid salt of a thyroid hormone is selected from the group consisting of levothyroxine pamoate and liothyronine pamoate.

134. The process for the preparation of an organic acid salt of a thyroid hormone of claim 32 wherein said alkali earth salt of said thyroid hormone is selected from sodium liothyronine and sodium levothyroxine.

135. The process for the preparation of an organic acid salt of a thyroid hormone of claim 32 further comprising isolating a polymorph of said organic acid salt of a thyroid hormone.

136. The process for the preparation of an organic acid salt of a thyroid hormone of claim 32 wherein at least one of said first mixture and said organic acid mixture is a liquid.

137. The process for the preparation of an organic acid salt of a thyroid hormone of claim 32 wherein at least one of said first mixture and said organic acid mixture is a solid.

33. A process for the preparation of a purified thyroid hormone comprising the steps of:

obtaining a first mixture comprising at least one thyroid hormone selected from liothyronine and levothyroxine;

reacting said first mixture with an organic acid wherein said organic acid comprises at least one aromatic ring substituted with at least one hydroxyl group and at least one carboxyl group in an ortho relationship to one another thereby forming an organic acid salt of said thyroid hormone.

138. The process for the preparation of a purified thyroid hormone of claim 33 further comprising isolating said organic acid salt of said thyroid hormone.

139. The process for the preparation of a purified thyroid hormone of claim 33 wherein said first mixture is a liquid.

140. The process for the preparation of a purified thyroid hormone of claim 33 wherein said first mixture is a solid.

34. A pharmaceutical composition comprising the salt of a thyroid hormone selected from the group consisting of levothyroxine and liothyronine and a stoichiometric amount of an organic acid comprising at least one aromatic ring having at least one hydroxyl moiety and at least one carboxylic acid moiety in an ortho relationship wherein said salt is stable for at least one year to variations in at least one of water content, heat, light, oxidative conditions and pH changes as indicated by said stoichiometric amount varying by less than 5% as measured by chromatographic techniques.

141. The pharmaceutical composition of claim 34 wherein said organic acid is defined as

142. The pharmaceutical composition of claim 141 wherein said organic acid is defined as

143. The pharmaceutical composition of claim 141 wherein said organic acid is defined as

144. The pharmaceutical composition of claim 141 wherein said organic acid is defined as

145. The pharmaceutical composition of claim 141 wherein said organic acid is defined as

146. The pharmaceutical composition of claim 141 wherein said organic acid is defined as

147. The pharmaceutical composition of claim 141 wherein said organic acid is defined as

148. The pharmaceutical composition of claim 34 wherein said organic acid is selected from the group consisting of pamoic acid, disodium pamoate, di-ammonium pamoate, di-potassium pamoate, di-alkyl and/or di-aryl amine pamoate, di-alkyl and/or di-aryl esters of pamoic acid, and di-alkylacyl and/or di-arylacyl O-esters of pamoic acid.

149. The pharmaceutical composition of claim 148 wherein said organic acid is selected from the group consisting of pamoic acid and disodium pamoate.

150. The pharmaceutical composition of claim 34 wherein said thyroid hormone and said organic acid are in a stoichiometric ratio of 1:

1 to 2;

1.

151. The pharmaceutical composition of claim 34 wherein said thyroid hormone and said organic acid are in a stoichiometric ratio of 1:

1.

152. The pharmaceutical composition of claim 34 wherein said thyroid hormone and said organic acid are in a stoichiometric ratio of 2:

1.

153. The pharmaceutical composition of claim 34 comprising 25-300 μ

g of said thyroid hormone.

154. The pharmaceutical composition of claim 34 in a form selected from a pill, a tablet, a capsule, a solution, a suspension injection dose, a transdermal patch and an inhalation formulation.

155. A drug product comprising said pharmaceutical composition of claim 34.

156. The pharmaceutical composition of claim 34 further comprising at least one additive selected from an excipient, a processing aid and a buffer.

157. The pharmaceutical composition of claim 34 wherein said salt comprises liothyronine pamoate with a differential scanning calorimetry thermogram of FIG. 1.

158. The pharmaceutical composition of claim 34 wherein said salt comprises liothyronine pamoate with a Fourier Transform Infrared spectrum of FIG. 2.

159. The pharmaceutical composition of claim 34 wherein said salt comprises liothyronine pamoate with a Powder X-Ray Diffraction diffractogram of FIG. 3.

160. The pharmaceutical composition of claim 34 wherein said salt comprises liothyronine pamoate with a proton nuclear magnetic resonance spectrum of FIG. 4.

161. The pharmaceutical composition of claim 34 wherein said salt comprises liothyronine pamoate with a high pressure liquid chromatograph chromatogram of FIG. 5.

162. The pharmaceutical composition of claim 34 wherein said comprises levothyroxine pamoate with a differential scanning calorimetry thermogram of FIG. 9.

163. The pharmaceutical composition of claim 34 wherein said salt comprises levothyroxine pamoate with a Fourier Transform Infrared spectrum of FIG. 10.

164. The pharmaceutical composition of claim 34 wherein said salt comprises levothyroxine pamoate with a Powder X-Ray Diffraction diffractogram of FIG. 11.

165. The pharmaceutical composition of claim 34 wherein said salt comprises levothyroxine pamoate with a proton nuclear magnetic resonance spectrum of FIG. 12.

166. The pharmaceutical composition of claim 34 wherein said salt comprises levothyroxine pamoate with an HPLC chromatogram of FIG. 13.

167. The pharmaceutical composition of claim 34 wherein said salt of a thyroid hormone is selected from the group consisting of levothyroxine pamoate and liothyronine pamoate.