OBJECTIVE: To assess the pharmacokinetic equivalence of a new soft capsule 
formulation of levothyroxine versus a marketed reference product and to assess 
the soft capsule formulated with stricter potency guidelines versus the capsule 
before the implementation of the new potency rule.
METHOD: Two single-dose randomized two-way crossover pharmacokinetic equivalence 
studies and one dosage form proportionality single-dose study comparing low, 
medium, and high strengths of the new formulation. All three studies were 
performed in a clinical setting. Participants were healthy male and female adult 
subjects with normal levothyroxine levels. A total of 90 subjects participated 
in the three studies.
RESULTS: Pharmacokinetic parameters were calculated on baseline- adjusted 
concentrations. The first pharmacokinetic equivalence study compared the 
levothyroxine sodium soft capsule formulation (Tirosint) with the reference 
Synthroid tablets and the two products were considered bioequivalent. The dosage 
form proportionality study compared the 50-, 100-, and 150-μg test capsules 
strengths dosed at the same level (600 μg) and all three strengths were 
considered equivalent when given at the same dosage. The last study compared the 
test capsule used in the first two studies with a new capsule formulation 
following the new potency guideline (±5%) set forward by the Food and Drug 
Administration and the two capsules were considered bioequivalent. Doses were 
well tolerated by subjects in all three studies with no serious adverse events 
reported.
CONCLUSIONS: The levothyroxine soft capsule formulated with the stricter new 
potency guideline set forward by the Food and Drug Administration met 
equivalence criteria in terms of rate and extent of exposure under fasting 
conditions to the reference tablet formulation. Clinical doses of the capsule 
formulation can be given using any combination of the commercialized strengths.