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

Area of Science:

• Pharmaceutical Sciences
• Drug Stability
• Formulation Development

Background:

• Sodium levothyroxine pentahydrate (LTSS) is a synthetic hormone with a narrow therapeutic index.
• Excipient interactions can significantly reduce the therapeutic activity of LTSS.
• Understanding these interactions is vital for developing stable and effective generic formulations.

Purpose of the Study:

• To evaluate the influence of common pharmaceutical excipients on the stability of sodium levothyroxine pentahydrate (LTSS).
• To identify specific excipients that are incompatible with LTSS under ambient and thermal stress conditions.
• To provide guidance for the selection of appropriate excipients in future LTSS solid formulation development.

Main Methods:

• Binary mixtures of LTSS with ten different pharmaceutical excipients were prepared.
• Universal attenuated total reflectance-Fourier transform infrared (UATR-FTIR) spectroscopy was used to analyze samples under ambient conditions.
• Thermoanalytical techniques (Thermogravimetry/Derivative Thermogravimetry/Heat Flow) were employed to assess interactions during thermal stress.

Main Results:

• UATR-FTIR spectroscopy revealed interactions between LTSS and specific excipients.
• Thermal analysis indicated that lactose, mannitol, and sorbitol induce instability in LTSS.
• No significant interactions were observed with starch, gelatin, calcium lactate pentahydrate, magnesium stearate, Tylose, Aerosil, or talc.

Conclusions:

• LTSS demonstrates incompatibility with lactose, mannitol, and sorbitol.
• These incompatible excipients should be avoided in the development of new generic solid formulations of LTSS.
• The study provides essential data for ensuring the stability and therapeutic efficacy of levothyroxine formulations.