Possible leaching of diethyl phthalate into levothyroxine sodium tablets.

The possible leaching of diethyl phthalate into four currently marketed brands of levothyroxine sodium tablets was investigated. Several strengths of levothyroxine sodium tablets and sizes of containers were used. Samples were analyzed by high-performance liquid chromatography (HPLC) to determine the levothyroxine sodium content and to determine if any unidentified compounds were present. The packaging for the four brands of tablets was also analyzed by using the same HPLC system to determine if any extractable compounds could be detected in the tablets. The potencies of the four brands of tablets were comparable. The tablets from the 100-count container of one brand (brand A) were the only tablets found to contain an unidentified peak in the chromatogram. The desiccants from the bottle showed the same unidentified compound, while the bottle and closure did not yield the peak. Thin-layer chromatography and HPLC identified the peak as diethyl phthalate, a plasticizer in the desiccant. Tablets, bottles, closures, and desiccants for the 1000-count brand A product and all sizes of the other brands were negative for the presence of diethyl phthalate. The desiccants in those containers were from a different manufacturer than the desiccant in the brand A 100-count bottle. Diethyl phthalate in the desiccant in 100-count bottles of brand A levothyroxine sodium tablets appeared to have leached into the tablets.

Levothyroxine sodium tablets: chemical equivalence and bioequivalence.

Two brands of levothyroxine sodium tablets were compared in vivo for bioequivalence in a double-blind, randomized study. The tablets were identical in levothyroxine content. Evaluation was by means of triiodothyronine (uptake), tetraiodothyronine, free thyroxine index, total triiodothyronine by radioimmunoassay, and thyroid-stimulating hormone measurements. No differences in clinical response were found in a study with a high statistical power. It was concluded that the two brands were bioequivalent because of chemical equivalence, use of micronized levothyroxine powder in tablet production with at least one of the brands, and scrupulous attention to quality control during the manufacturing process, all of which contributed to assurance of homogeneity of the products and close adherence (+/- five percent) to the claimed potency.