Stability of caffeine oral formulations for neonatal use

The stability of an oral formulation of 10 mg/ml caffeine citrate (equivalent to 5.03 mg/ml caffeine free base), which was preserved with potassium sorbate, was assessed at a range of temperatures. There was no appreciable change in pH or caffeine content over 1 year, even at storage temperatures of 32 degrees C and 45 degrees C. A batch-to-batch difference in the stability of potassium sorbate was detected, with losses over 1 year of 2% and 11% for two batches at 25 degrees C and 10% and 30%, respectively, at 45 degrees C. The formulation complied with the Antimicrobial Preservative Efficacy test of the British Pharmacopoeia throughout a period of storage at 25 degrees C for 1 year. There was no detectable benefit to preservative efficacy by adding 20% w/v sorbitol as an osmotic agent. The formula with no sorbitol may be preferable due to the potential for sorbitol to cause gastrointestinal upset. A shelf-life of 1 year at room temperature is feasible. The additional precaution of limiting the in-use storage life to 1 month after opening is recommended to ensure acceptable microbiological quality.