Stability and Compatibility Studies of Levothyroxine Sodium in Solid Binary Systems—Instrumental Screening

Abstract

The influence of excipients on the stability of sodium levothyroxine pentahydrate (LTSS) under ambient conditions and thermal stress was evaluated. Since LTSS is a synthetic hormone with a narrow therapeutic index, the interactions of LTSS with excipients can lead to a drastic diminution of therapeutic activity. Ten commonly used pharmaceutical excipients with different roles in solid formulations were chosen as components for binary mixtures containing LTSS, namely, starch, anhydrous lactose, D-mannitol, D-sorbitol, gelatin, calcium lactate pentahydrate, magnesium stearate, methyl 2-hydroxyethyl cellulose (Tylose), colloidal SiO2 (Aerosil) and talc. As investigational tools, universal attenuated total reflectance- Fourier transform infrared spectroscopy UATR-FTIR spectroscopy and thermal analysis were chosen and used as follows: UATR-FTIR spectra were drawn up for samples kept under ambient conditions, while thermoanalytical tools (TG/DTG/HF data) were chosen to evaluate the inducing of interactions during thermal stress. The corroboration of instrumental results led to the conclusion that LTSS is incompatible with lactose, mannitol and sorbitol, and these excipients should not be considered in the development of new generic solid formulations.

Investigating the Influence of Excipients on the Stability of Levothyroxine Sodium Pentahydrate

“…The chemical stability of levothyroxine sodium has been comprehensively investigated and has been the subject of numerous publications. − ,,, However, the role of excipients, and specifically the combined effects of formulation components and processing conditions on the chemical stability, is not completely understood. , Solution based methods such as HPLC, in light of their specificity and sensitivity, are used to assess the chemical stability of the API in dosage forms. Such an approach does not enable a comprehensive understanding of the stability behavior of LSP in tablet formulations.…”

Levothyroxine Sodium Pentahydrate Tablets – Formulation Considerations

“…The same mixtures were also subjected to thermal analyses (DSC and TGA). 112 By combining the results from the two techniques, the authors concluded that levothyroxine sodium was incompatible with sucrose, mannitol and sorbitol.…”

“…drug substance) and in marketed drug products has been extensively investigated. [111][112][113][114][115][116] Our objective is to comprehensively review the factors affecting the stability of levothyroxine sodium when formulated as a solid oral dosage form. The term 'stability' encompasses both chemical and physical stability.…”

Stability of levothyroxine tablets in blister packaging versus bottles and vials under simulated in-use conditions

“…Excipients have been shown to impact levothyroxine stability (Collier et al 2010;Ledeți et al 2020;Patel et al 2003), and differences in tablets from different manufacturers beyond packaging (e.g., size, geometry, surface area, coated or not coated) could also potentially impact physicochemical properties and stability. However, these were not considered in this study as the goal was to assess stability of levothyroxine in the forms and packaging currently available to patients.…”