Levothyroxine stability and shelf life
Pro Research Analysisby 
Searched over 200M research papers
Levothyroxine Stability: Key Factors and Degradation Risks
Levothyroxine is known for its sensitivity to environmental conditions, excipients, and packaging, which can significantly impact its stability and shelf life. The drug is classified as a narrow therapeutic index medication, making consistent potency and stability critical for patient safety and therapeutic effectiveness 310.
Environmental Conditions: Temperature, Humidity, and Light
Levothyroxine degrades more rapidly at higher temperatures and humidity. Studies show that extemporaneously prepared syrups and oral liquids from tablets have a short shelf life, retaining potency for only about 8–15 days when refrigerated at 4–5°C, and even less at room temperature 15. Exposure to direct sunlight can cause up to 40% potency loss in tablets within just 10 days, highlighting the importance of protecting the drug from light . Real-time stability studies indicate that tablets can fall out of specification (below 90% potency) within 15–20 months, and lose more than 5% potency after just 8–9 months at room temperature .
Role of Excipients in Levothyroxine Stability
The choice of excipients in tablet formulations is crucial. Certain excipients, such as crospovidone, povidone, sodium lauryl sulfate, and carbohydrates like lactose, dextrose, and starch, can accelerate levothyroxine degradation through chemical reactions such as deiodination, deamination, and Maillard condensation 469. Tablets containing lactose are particularly prone to forming Maillard reaction products, which can increase over time but are not considered toxic at the levels typically found at the end of shelf life . Using basic pH modifiers (e.g., sodium carbonate, sodium bicarbonate, magnesium oxide) or excipients like dibasic calcium phosphate and mannitol can improve stability and help tablets meet potency requirements for longer periods 67.
Packaging and Storage: Impact on Shelf Life
Packaging plays a significant role in maintaining levothyroxine stability. Blister packaging, especially aluminum/aluminum cold form blisters, provides superior protection against moisture and light compared to bottles or pharmacy vials. Tablets stored in blister packs maintained their potency (about 99.6% after 105 days), while those in bottles dropped below 94% potency over the same period . This suggests that blister packaging is preferable for preserving the drug’s integrity during storage and use.
Advances in Formulation for Improved Shelf Life
Recent reformulations of levothyroxine tablets have focused on meeting stricter regulatory standards for potency and stability, ensuring that the active drug remains within 95–105% of the labeled amount throughout a shelf life of up to 3 years, even in challenging climate zones . These new formulations allow for consistent dosing and reduce the need for frequent retitration or additional thyroid function testing when switching products.
Conclusion
Levothyroxine’s stability and shelf life are influenced by temperature, humidity, light exposure, excipient selection, and packaging. To maximize shelf life and maintain potency, levothyroxine should be stored in protective blister packaging, away from heat and light, and formulated with excipients that do not promote degradation. Newer formulations and packaging technologies have significantly improved the drug’s stability, supporting safer and more effective use for patients with hypothyroidism 23467910.
Sources and full results
Most relevant research papers on this topic