Physicochemical stability of a polysorbate-80-containing solvent compounded in the hospital pharmacy and used to reconstitute a biologic for nebulisation.

Abstract

Objectives: To assess the long-term physicochemical stability of a solvent (10 mM phosphate buffer pH 6.5 containing sodium chloride (145 mM) and polysorbate 80 (PS80) 0.02%) used to reconstitute a biologic for nebulisation. The solvent was compounded in the hospital pharmacy and stored in amber glass vials at -20°C for 1 year.

Methods: Samples were analysed immediately on compounding and then 1, 3, 6, 9 and 12 months after storage at -20°C (immediately after thawing, and also 1 month later keeping the vials at 2-8°C). The assays included a visual examination, measurement of the pH, osmolality, sub-visible particulate contamination, the concentration of PS80, and the concentration of oleic acid and peroxides (both major markers of PS80 degradation). Quantification of PS80 was challenging due to the substance's molecular heterogeneity and the lack of a good chromophore. The strategy adopted consisted of hydrolysis in a strong base and then liquid-liquid extraction of the oleic acid (PS80's hydrolysis product). The oleic acid content was determined using reversed phase high performance liquid chromatography with ultraviolet detection. The peroxide content was determined spectrophotometrically using a ferrous oxidation with xylenol orange assay.

Results: Over 12 months, there was no significant change in the samples' visual appearance, pH and osmolality. The PS80 concentration remained above 90% of the initial value. The subvisible particle counts remained far below the European Pharmacopoeia thresholds. The oleic acid content of the non-hydrolysed samples remained constant, and no peroxide was detected.

Conclusions: A PS80-containing solvent is stable for 1 year when stored at -20°C (±5°C) in amber glass vials. Moreover, the solvent is stable for up to 1 month after thawing if stored at 2-8°C.