Levothyroxine compositions and methods
First Claim
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1. An immediate release pharmaceutical composition comprising a levothyroxine salt.
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Abstract
The present invention generally relates to stable pharmaceutical compositions, and methods of making and administering such compositions. In one aspect, the invention features stabilized pharmaceutical compositions that include pharmaceutically active ingredients such as levothyroxine (T4) sodium and liothyronine (T3) sodium (thyroid hormone drugs), preferably in an immediate release solid dosage form. Also provided are methods for making and using such immediate release and stabilized compositions.
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Citations
127 Claims
- 1. An immediate release pharmaceutical composition comprising a levothyroxine salt.
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56. An immediate release pharmaceutical composition in tablet form comprising levothyroxine sodium, the composition comprising:
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a) between from about 0.01 mg/tablet to about 500 mg/tablet levothyroxine sodium (USP);
b) between from about 100 mg/tablet to about 110 mg/tablet of microcrystalline β
-cellulose, NF (Ceolus®
) having a bulk density of between from about 0.10 g/cm3 to about 0.35 g/cm3;
c) between from about 25 mg/tablet to about 50 mg/tablet of croscarmellose sodium, NF (Ac-di-sol); and
d) between from about 0.5 mg/tablet to about 5 mg/tablet of magnesium stearate, NF. - View Dependent Claims (57, 59)
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61. A method of making an immediate release pharmaceutical composition comprising a levothyroxine salt, the method comprising
a) mixing a levothyroxine salt with microcrystalline β - -cellulose and a croscarmellose salt to make a blend; and
b) compressing the blend in a ratio of initial volume to final volume of between from about 2;
1 to about 5;
1 to make the composition. - View Dependent Claims (62, 63, 64)
- -cellulose and a croscarmellose salt to make a blend; and
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66. A method of making a stabilized pharmaceutical composition comprising a levothyroxine salt, the method comprising
a) mixing a levothyroxine salt with microcrystalline β - -cellulose and a croscarmellose salt to make a blend; and
b) compressing the blend in a ratio of initial volume to final volume of between from about 2;
1 to about 5;
1 to make the composition. - View Dependent Claims (67, 68, 69, 70)
- -cellulose and a croscarmellose salt to make a blend; and
- 71. A stabilized, immediate release pharmaceutical composition comprising a levothyroxine.
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78. A stabilized pharmaceutical composition comprising levothyroxine, wherein the composition exhibits a levothyroxine (T4) plasma Cmax of between from about 10 μ
- g/dl to about 20 μ
g/dl as determined by a standard Cmax test. - View Dependent Claims (79, 80, 81)
- g/dl to about 20 μ
- 82. A stabilized pharmaceutical composition comprising levothyroxine, wherein the composition exhibits a triiodothyronine (T3) plasma Tmax of between from about 10 hours to about 20 hours as determined by the standard Tmax test.
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84. A stabilized immediate release pharmaceutical composition comprising levothyroxine, wherein the composition exhibits a levothyroxine (T4) plasma Tmax of between from about 0.5 hours to about 5 hours as determined by a standard Tmax test.
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85. A composition of claim 85, wherein the composition exhibits a levothyroxine (T4) plasma Tmax of between from about 1 hour to about 3 hours as determined by the standard Tmax test.
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86. A pharmaceutical composition, comprising the product of dissolution of a preparation comprising levothyroxine, cross-linked sodium carboxymethylcellulose, and β
- -form microcrystalline cellulose, in an aqueous medium.
- View Dependent Claims (87)
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88. An immediate release pharmaceutical composition comprising levothyroxine, wherein at least about 85% of the levothyroxine dissolves in aqueous solution in less than about 20 minutes as determined by a standard dissolution test.
- 90. A stabilized pharmaceutical composition comprising levothyroxine, wherein at least about 85% of the levothyroxine dissolves in aqueous solution in less than about 20 minutes as determined by a standard dissolution test.
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92. An immediate release pharmaceutical composition comprising levothyroxine, wherein the composition is essentially sugar free.
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93. A stabilized pharmaceutical composition comprising levothyroxine, wherein the composition is essentially sugar free.
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94. An immediate release pharmaceutical composition comprising levothyroxine, wherein the composition is essentially non-granular.
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95. A stabilized pharmaceutical composition comprising levothyroxine, wherein the composition is essentially non-granular.
- 96. An immediate release pharmaceutical composition comprising levothyroxine, wherein the composition has a post-packaging potency of between from about 95% to about 120% as determined by a standard potency test.
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98. A stabilized pharmaceutical composition comprising levothyroxine, wherein the composition has a post-packaging potency of between from about 95% to about 120% as determined by a standard potency test.
- 100. An immediate release pharmaceutical composition comprising levothyroxine, wherein the composition is formulated as a tablet.
- 103. A stabilized pharmaceutical composition comprising levothyroxine, wherein the composition is formulated as a tablet.
- 106. An immediate release pharmaceutical composition comprising levothyroxine, wherein the tablet is configured to increase heat transfer away from the tablet.
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111. A stabilized pharmaceutical composition comprising levothyroxine, wherein the tablet is configured to increase heat transfer away from the tablet.
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116. A method of instructing a human to take an immediate release pharmaceutical composition in tablet form comprising levothyroxine for reduced or absent thyroid function, said method comprising:
instructing the human to take a certain number of the immediate release pharmaceutical levothyroxine tablets a selected number of times daily to treat reduced or absent thyroid function. - View Dependent Claims (117)
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118. A method of instructing a human to take a stabilized, immediate release pharmaceutical composition in tablet form comprising levothyroxine for reduced or absent thyroid function, said method comprising:
instructing the human to take a certain number of the immediate release pharmaceutical levothyroxine tablets a selected number of times daily to treat reduced or absent thyroid function. - View Dependent Claims (119)
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120. A method of instructing a human to take an effective amount of an immediate release pharmaceutical composition in tablet form comprising levothyroxine to treat a thyroid indication selected from the group consisting of replacement or supplemental therapy in hypothyroidism, suppression of pituitary TSH secretion, prevention of euthyroid goiters and adjunctive therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer said method comprising
administering to the human an effective number of the immediate release pharmaceutical levothyroxine tablets a selected number of times daily to treat said thyroid indication.
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121. A method of instructing a human to take an effective amount of a stabilized, immediate release pharmaceutical composition in tablet form comprising levothyroxine to treat a thyroid indication selected from the group consisting of replacement or supplemental therapy in hypothyroidism, suppression of pituitary TSH secretion, prevention of euthyroid goiters and adjunctive therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer, said method comprising
administering to the human an effective number of the stabilized, immediate release pharmaceutical levothyroxine tablets a selected number of times daily to treat said thyroid indication.
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122. A method of treating a human with an immediate release pharmaceutical composition in tablet form comprising levothyroxine for reduced or absent thyroid function, said method comprising:
administering to the human an effective number of the immediate release pharmaceutical levothyroxine tablets a selected number of times daily to treat reduced or absent thyroid function. - View Dependent Claims (123)
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124. A method of treating a human with a stabilized, immediate release pharmaceutical composition in tablet form comprising levothyroxine for reduced or absent thyroid function, said method comprising:
administering to the human an effective number of the immediate release pharmaceutical levothyroxine tablets a selected number of times daily to treat reduced or absent thyroid function. - View Dependent Claims (125)
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126. A method of treating a human with an effective amount of an immediate release pharmaceutical composition in tablet form comprising levothyroxine for a thyroid indication selected from the group consisting of replacement or supplemental therapy in hypothyroidism, suppression of pituitary TSH secretion, prevention of euthyroid goiters and adjunctive therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer, said method comprising
administering to the human an effective number of the immediate release pharmaceutical levothyroxine tablets a selected number of times daily to treat said thyroid indication.
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127. A method of treating a human with an effective amount of a stabilized, immediate release pharmaceutical composition in tablet form comprising levothyroxine to treat a thyroid indication selected from the group consisting of replacement or supplemental therapy in hypothyroidism, suppression of pituitary TSH secretion, prevention of euthyroid goiters and adjunctive therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer, said method comprising:
administering to the human an effective number of the stabilized, immediate release pharmaceutical levothyroxine tablets a selected number of times daily to treat said thyroid indication.
Specification