Development of levothyroxine sodium pediatric oral solution driven by STEP database: Stability study and degradation...

Area of Science:

• Pharmaceutical Sciences
• Drug Development
• Pediatric Formulations

Background:

• Levothyroxine sodium (SLT4) is the primary oral treatment for hypothyroidism.
• Congenital hypothyroidism is a leading preventable cause of intellectual disability.
• Current oral SLT4 formulations (tablets) pose challenges for pediatric patients and adults who cannot swallow, necessitating extemporaneous preparation.

Purpose of the Study:

• To develop a stable oral liquid formulation of levothyroxine sodium (SLT4).
• To assess the stability of the SLT4 oral solution under various storage conditions and packaging.
• To provide a safe and flexible alternative for hypothyroidism treatment in patients with swallowing difficulties.

Main Methods:

• Excipient selection for pediatric safety using data tools (STEP and PERA).
• Development and validation of an HPLC method for SLT4 quantification.
• Stability testing over 63 days at 4°C, 25°C, and 40°C in amber glass bottles and sachets.
• Forced degradation studies using UPLC-MS to identify degradation products.

Main Results:

• The developed SLT4 oral solution (30 µg/mL) exhibited appropriate physicochemical and microbiological characteristics.
• The formulation demonstrated stability for 63 days when stored at 4°C and 25°C in both sachet and amber glass bottle packaging.
• Six major degradation product structures were elucidated following stress testing.

Conclusions:

• A simple, stable levothyroxine sodium oral solution with pediatric-safe excipients was successfully developed.
• The formulation offers dosing flexibility and represents a viable alternative for hospital-based hypothyroidism treatment.
• This oral liquid formulation addresses the unmet need for patients unable to swallow conventional SLT4 tablets.