Action and use
Thyroid hormone replacement.
Definition
Levothyroxine Tablets contain Levothyroxine Sodium.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Production
Levothyroxine Sodium used in the formulation of Levothyroxine Tablets exists primarily in its most stable form, a crystalline pentahydrate.
Care should be taken during manufacture to avoid exposure to higher temperatures (> 50°) or very low humidities.
Content of anhydrous levothyroxine sodium, C15H10I4NNaO4
90.0 to 105.0% of the stated amount.
Identification
A. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the peak in the chromatogram obtained with solution (2).
B. To a quantity of the powdered tablets containing the equivalent of 0.5 mg of anhydrous levothyroxine sodium add a mixture of 3 ml of
ethanol (50%) and 0.2 mL of
hydrochloric acid, boil gently for 30 seconds, cool, filter, add 0.1 mL of a 10% w/v solution of
sodium nitrite and boil; a yellow colour is produced. Cool and make alkaline with 5
m ammonia; the solution becomes orange.
Tests
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
Plastic containers must not be used to prepare and store solutions.
test conditions
(a) Use Apparatus 2, rotating the paddle at 100 revolutions per minute.
(b) Use 500 mL of
water, at a temperature of 37°, as the medium.
(c) For tablets containing the equivalent of 25 µg or less of anhydrous levothyroxine sodium, place two tablets in the dissolution vessel; for tablets containing more than the equivalent of 25 µg of anhydrous levothyroxine sodium, place one tablet in the dissolution vessel.
procedure
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) After 45 minutes withdraw a 5 mL sample of the medium and centrifuge, dilute with sufficient of the dissolution medium, if necessary, to produce a solution expected to contain 0.00001% w/v of Levothyroxine Sodium. To a 5 mL aliquot add 200 µL of 0.1
m sodium hydroxide and 125 µL of a 2% v/v solution of
diethylamine.
chromatographic conditions
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 225 nm.
(f) Inject 150 µL of each solution.
mobile phase
5 volumes of orthophosphoric acid, 300 volumes of acetonitrile R1 and 700 volumes of water.
determination of content
Calculate the total content of levothyroxine sodium, C15H10I4NNaO4, in the medium from the chromatograms obtained and using the declared content of C15H10I4NNaO4 in levothyroxine sodium EPCRS.
LIMITS
The amount of levothyroxine released is not less than 75% (Q) of the stated amount.
Uniformity of content
Comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Add sufficient 0.05
m sodium hydroxide to one tablet to produce a solution containing the equivalent of about 6 µg per mL of anhydrous levothyroxine sodium, mix with the aid of ultrasound until the tablet is fully dispersed, cool and shake for 2 minutes. Add sufficient 0.05
m sodium hydroxide to produce a solution containing the equivalent of 0.0004% w/v of anhydrous levothyroxine sodium, filter through glass microfibre filter (Whatman GF/C is suitable) and use the filtrate.
chromatographic conditions
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 225 nm.
(f) Inject 20 µL of each solution.
mobile phase
5 volumes of orthophosphoric acid, 300 volumes of acetonitrile and 700 volumes of water.
determination of content
Calculate the content of C15H10I4NNaO4 in each tablet using the declared content of C15H10I4NNaO4 in levothyroxine sodium EPCRS.
Assay
For tablets containing the equivalent of less than 2 mg and/or less than 2% w/w of anhydrous levothyroxine sodium
Use the average of the individual results determined in the test for Uniformity of content.
For tablets containing the equivalent of 2 mg or more and 2% w/w or more of anhydrous levothyroxine sodium
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D. Prepare a mixture of equal volumes of methanol and 0.1m sodium hydroxide (solvent A).
(1) Disperse with the aid of ultrasound for 10 minutes a quantity of the powdered tablets containing the equivalent of 0.1 mg of anhydrous levothyroxine sodium with 8 mL of solvent A. Shake for 2 minutes, cool, add sufficient solvent A to produce 10 mL, mix, filter through glass microfibre filter paper (Whatman GF/C is suitable) and use the filtrate.
chromatographic conditions
The chromatographic conditions described under Uniformity of content may be used.
system suitability
The assay is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 4.0.
determination of content
Calculate the content of C15H10I4NNaO4 in the tablets using the declared content of C15H10I4NNaO4 in levothyroxine sodium EPCRS.
Storage
Levothyroxine Tablets should be protected from light.
Labelling
The quantity of active ingredient is stated in terms of the equivalent amount of anhydrous levothyroxine sodium.