Optimisation of thawing conditions for solutions of cefuroxime in pre-filled syringes for intracameral injection to avoid a concentration gradient

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Study objective

The intracameral injection of cefuroxime has shown its effectiveness in the prevention of endophthalmitis consecutive to cataract surgery. The solution is generally loaded into syringes that are deep frozen to ensure stability before use. However, a concentration gradient has been found inside the syringes after thawing. We set out to determine the optimal thawing conditions that would ensure homogeneity.


Solutions of cefuroxime in pre-filled syringes were deep frozen at −20°C and thawed at 15, 20 and 25°C with or without homogenisation. Samples were taken from three segments of each syringe immediately after preparation and then 15, 30 and 60 min after removal from the freezer. Cefuroxime was assayed by high-performance liquid chromatography and temperature in the solution was monitored using a thermocouple. Measurement of pH, osmolality and particulate matter were also performed.


Before thawing, the cefuroxime concentration is homogeneous in the syringes. After 15 min of thawing at 15, 20 and 25°C without homogenisation, a steep concentration gradient is observed, with a variation in cefuroxime concentration of ±25-30% along the syringe. After 1 h of thawing, the concentration variations are narrower, about 15%. Manual homogenisation of the solutions gives a stable concentration after 15 min of thawing between 15 and 25°C, but the solution takes fully 30 min to reach the ambient temperature. The solution of cefuroxime displays a pH, an osmolality and a particle count that were compatible with intracameral injection.


This study demonstrates the need to let syringes containing cefuroxime thaw out for 30 min between 15 and 25°C and to homogenise the contents at least by inversion of the syringe before injecting into the patient. If this procedure is not followed, the patient may be exposed to overdosing or underdosing of cefuroxime according to whether the surgeon injects the first or the last 0.1 ml of the solution.

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