Background: Treatment outcome with hydrocortisone for congenital adrenal hyperplasia (CAH) in neonates and children is highly variable. As there is no licensed formulation for children <6 years hydrocortisone capsules individually have to be compounded by local pharmacies (dose strength: 0.59.5 mg). The aim of this study was to characterise mass and content of these capsules in order to assess medication safety for effective and nontoxic dosing in terms of precision of mass and drug concentration as well as accuracy of drug content in the compounded capsules.
Methods: 20 batches of 20 capsules each were analysed so far according to European Pharma-copoeia1. Precision of net capsule mass filling was investigated gravimetrically by substracting the chasing from the total capsule mass. Next, the mean mass per batch and % deviations from mean mass for each capsule were calculated (mass precision). For precision of drug content, an HPLC-UV method (Agilent Eclipse XDB C18 column; H2O: ACN 70:30, v/v) for hydrocortisone concentration was developed and validated2 also separating fludrocortisone potentially co-com-pounded. Mean concentration per batch was determined; for each capsule % deviation from mean concentration (content precision) as well as from nominal concentration were calculated (content accuracy).
Results: Mean concentration of hydrocortisone was 11.7% lower than the nominal one.
|Mass precision (%)||Content precision (%)||Content accuracy (%)|
|Single deviation ±7.5%/10%1||>7.5||Single deviation ±15%1||>7.3||38|
|Single deviation ±15%/20%1||>0||Single deviation ±25%1||>4.5||8.8|
|Batches that failed test1||20||Batches that failed test1||15||20|
Conclusions: Up to 20% of the batches did not meet the accuracy or precision criteria. Hence, therapy might be inadequate in up to every 5th child. The study demonstrates the need for improved medication safety in neonates and infants suffering from CAH.
Acknowledgements: Supported by the EC Framework 7 grant, TAIN No:281654.
1. European Pharmacopoeia, 8th ed. (2013), 2. EMA, Guideline on bioanalytical method validation (2012).
03 - 07 May 2014
European Society of Endocrinology