A Comparative pH-Dissolution Profile Analysis of Selected Commercial Levothyroxine Formulations in Lebanon Using Anion-Exchange HPLC Method: Implication on Interchangeability.

Abstract

Hypothyroidism is a common endocrine disorder that requires medical intervention by the administration of hormone replacement therapy: levothyroxine-a drug recognized as a NTI drug. Generic levothyroxine formulations can be considered as an economic alternative; however, bioequivalence problem has been encountered between various available levothyroxine formulations; thus, generic substitution is considered controversial. Dissolution testing is often used to assess the bioequivalence. The dissolution of levothyroxine from four pharmaceutical formulations: Euthyrox (old and new formulations), Eltroxin, and generic levothyroxine Sandoz was studied using a sensitive anion-exchange HPLC method. Dissolution profiles were compared using model-dependent and model-independent approaches. Results showed that there is significant difference between the formulations confirmed by the similarity (f ₁) and dissimilarity (f ₂) factors. All formulations showed variable and pH-dependent dissolution behaviors where at pH 1.2, the highest dissolution (almost 100%) is achieved. The drug-release kinetics model for each formulation varied depending on the dissolution media; where no unique kinetic model can be used to describe the release of levothyroxine from the tablets. The revealed variations in the in vitro dissolution profiles of the four formulations could be due to excipient variability from one brand to another affecting oral absorption and bioavailability and may be the reason behind bioequivalence problems between various formulations.