Comparative Pharmaceutical Evaluation and Bioavailability Assessment of Levothyroxine Sodium in Different Dosage Forms

Levothyroxine sodium is recognized as a narrow-therapeutic-index drug, making its clinical performance highly sensitive to formulation variables that can influence systemic bioavailability. This study focused on the development, physicochemical evaluation, and comparative bioavailability assessment of levothyroxine sodium formulated into three distinct dosage forms: tablets, HPMC based capsules, and soft gelatin capsules. Each formulation was manufactured using optimized processing strategies to ensure stability and dose accuracy. Physical evaluation and comprehensive in vitro testing, including assay, content uniformity, dissolution profiling, and analysis of related substances, were conducted in accordance with compendial standards. All three dosage forms exhibited satisfactory predefined quality criteria, indicating acceptable pharmaceutical performance. In vivo characterization was carried out in healthy volunteers using a randomized, open-label, two-treatment, two-period crossover design to compare the test products with the reference capsule. Blood samples were collected over an extended sampling period, and levothyroxine plasma concentrations were quantified using a validated analytical method. Pharmacokinetic parameters, including Cmax, AUC0–t, and AUC0–∞, were derived through non-compartmental analysis and evaluated for bioequivalence using standard statistical approaches. The in vivo results demonstrated that the soft gelatin capsules exhibited bioavailability parameters closely aligned with those of the reference product, with 90% confidence intervals for both rate and extent of absorption falling within accepted regulatory bioequivalence limits. Conversely, the directly compressed tablets and HPMC-based capsule formulations displayed higher inter-subject variability and did not consistently meet equivalence criteria across all pharmacokinetic endpoints. Among the dosage forms investigated, soft gelatin capsule provided the most reliable pharmaceutical quality and bioavailability performance relative to the reference product. These findings highlight the critical role of formulation design in achieving consistent levothyroxine exposure and support the liquid-filled soft gelatin system as a promising alternative for clinical application. Keywords: Levothyroxine sodium; Different dosage forms; Soft-gelatin capsules; Bioavailability; Bioequivalence.