Potassium sorbate: the ideal pediatric preservative?

Introduction
According to the European Pharmacopoeia (EP) recommendations, non-sterile pharmaceutical preparations are subject to microbiological quality acceptance criteria.
Potassium sorbate (PS) is a preservative with antimicrobial and antifungal properties. It appears to be an ideal preservative for pediatrics: it presents no contraindications unlike sodium benzoate and fewer notorious effects compared to parabens.

Objective
The aim of this study was to analyze the efficacy of PS in order to optimize its use in oral pharmaceutical preparations.

Methods
A total of 4 preparations were selected (atropine, riboflavin, phenobarbital and sulfadiazine) with different parameters (preservative concentration, pH, storage mode). A microbial preservation efficacy test is carried out (EP test 5.1.3). Microbial quality over time is also monitored by microbial enumeration (EP test 2.6.12) and detection of specified microorganisms (EP test 2.6.13) after validation of applicability. Each preparation includes 3 batches of 3 vials: one for stability evaluation before opening (D0), one for stability control at day 48 (D48) after opening each day, and one for stability at month 4 (M4) without opening.

Results
The antimicrobial preservation efficacy trial was conclusive on all preparations: after microbial inoculation with strains recommended by EP, no bacteria (TAMC) or yeasts/molds (TYMC) were observed at D14 and then at D28. The enumeration test showed an average of 13.3 TAMC colonies and 10.3 TYMC colonies in the atropine batches at D48, and an average of 0.3 TAMC colonies in the phenobarbital batches. At D48, no further colonies were observed. At M4, the enumeration test revealed an average of 0.3 TAMC colonies in the phenobarbital batches. No other colonies were observed at M4. Specific tests for E. Coli, Salmonella, S. Aureus and Gram-negative bacteria resistant to bile salts were negative at D48 and M4. A comparison of the various parameters was carried out.

Discussion/Conclusion
The least satisfactory results in terms of microbiological quality were obtained with the atropine solution, which had the lowest PS concentration (0.1%) and was the only solution kept refrigerated. PS appears to be effective under specific conditions: pH between 3 and 5 and concentration between 0.2% and 0.3%. These results confirm the data in the literature¹: efficacy is reduced when the temperature is lowered.
¹ Handbook of Pharmaceutical Excipients, Sixth edition