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August 15, 1980

Standards for Levothyroxine Preparations

Author Affiliations

Food and Drug Administration Rockville, Md

JAMA. 1980;244(7):658-659. doi:10.1001/jama.1980.03310070012008

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To the Editor.—  Jacobson and coworkers (243:733, 1980) recently presented their experience on the nonequality of two thyroxine preparations. They demonstrated that the 100-μg tablets from Letter and Synthroid were physiologically nonbioequivalent and therefore should not be dispensed interchangeably. We sympathize with their observations from a drug quality viewpoint. The nonequivalence of various thyroxine preparations may stem from the fact that different firms are using raw material (levothyroxine sodium) of different particle size during the manufacturing process. Because of the low solubility of levothyroxine sodium, some firms are employing micronization techniques to enhance solubility, whereas others are using raw material with larger particle size that complies with the requirements of the United States Pharmacopeia. These differences may appear to be minor in nature; however, in this product they have a significant effect on the bioavailability of the active material. The current USP recognizes the effect of particle size on bioavailability;