Manipulating prednisolone tablets for paediatric adjustments - dose accuracy and precision

To understand dose accuracy after manipulating prednisolone tablets.

Prednisolone is a widely used drug for adult patients but also in paediatrics where tablets are manipulated to facilitate smaller doses and/or oral administration.

Prednisolone tablets of 2.5 mg and 5 mg from Orifarm and Alternova, as well as a pharmacy compounded suspension of 1 mg/mL, were tested. Quantification of prednisolone in various fragments and volumes related to the manipulations were carried out using a validated ultra high-pressure liquid chromatography (UHPLC) method.

When tablets were split into halves and quarters, the accuracy of the best halves and the best quarters were within ±15%. When the fragments were further dispersed in an oral syringe to aid oral administration, 6% of prednisolone was lost on average. The syringes could be stored for at least 6 hours without any further loss. The more laborious method of first dispersing tablets, followed by withdrawing a fraction, did not improve neither accuracy nor precision compared with simple splitting. But by focusing on some crucial steps, this method could produce doses as low as 0.25 mg with an accuracy of ±20%. Nevertheless, the accuracy improved to ±10% when the compounded suspension was used. The precision was also higher.

When tablets were split into two and four fragments, the accuracy of the largest half and second largest quarter were within a clinically acceptable range. In cases of tapering before discontinuing prednisolone, a higher accuracy might be required, and pharmacy compounded suspensions should then be considered, if available.