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

Abstract

Abstract Introduction Levothyroxine, the standard-of-care treatment for hypothyroidism, is susceptible to degradation when exposed to light and moisture and is an FDA-designated narrow therapeutic index drug. In this report, we examined how different packaging (e.g., cold form blister packs, manufacturer’s bottles, or pharmacy amber vials) affects the physicochemical integrity and potency of levothyroxine in conditions simulating real-world patient use. Methods In part 1 of this study, we evaluated changes in the physicochemical properties (e.g., moisture gain, hardness, and disintegration time) of levothyroxine tablets stored in high-density polyethylene (HDPE) bottles, amber vials, and blister packs when exposed intermittently to different relative humidities (RH), 25 °C/75% RH and 25 °C/90% RH for 90 days, or 54 °C/75% RH continuously for 2 days. In part 2 of the study, we compared the potency of levothyroxine tablets in bottles and aluminum/aluminum cold form blister packs exposed to 28 °C/65% RH intermittently over 105 days and continuously over 30 days. Results Moisture content, hardness, and disintegration time were relatively unchanged for blister-packaged levothyroxine tablets under all conditions studied. Conversely, the physicochemical properties of tablets stored in amber vials and bottles were altered over time. Levothyroxine potency remained relatively consistent for blister-packaged tablets (100.8% at baseline, 99.6% at day 105) and decreased for bottled levothyroxine (101.4% at baseline to 93.9% at day 105). Conclusion Levothyroxine packaging can influence tablet integrity. Blister packages preserved physicochemical properties and potency better than bulk bottles. Additional studies are needed to determine the impact of packaging and changes in tablet integrity on patient outcomes.

Keywords

• Levothyroxine
• Blister packaging
• Stability
• Humidity
• Potency