The pharmaceutical industry currently falls short in meeting the pediatric medication requirements, including indications, dosages validated by clinical trials, and formulations tailored to this population [1,2]. Specifically, in children under 8 years old, solid oral forms are not recommended due to the risk of misdirection. Consequently, emphasis should be placed on liquid oral forms [3]. In France, spironolactone is exclusively available in tablet form, with the smallest dosage being 25 mg (12.5 mg for half a tablet) [4]. Considering the recommended dosage in children varies from 1 to 3 mg/kg QD or BID the commercial form does not allow for optimal dosage adjustment [4]. Caregivers and parents are often left to crush the tablet form, dilute in an appropriate solvent and administer approximately the right dose prescribed [2]. A recent study has demonstrated that such manipulations result in dramatic underdosing and high inter-dose variability, whereas extemporaneously compounded oral suspensions enable more accurate dosing [5]. When age-appropriate commercial products are lacking, compounded suspensions thus represent a safer and more reliable alternative.

Spironolactone, a competitive antagonist diuretic of the aldosterone receptor (a mineralocorticoid steroid hormone), acts on the distal convoluted tubule and collecting tubule of the nephron [4]. Its primary indication in neonatal intensive care and neonatal cardiology is for managing stage III or IV heart failure (off-label) in the context of congenital heart disease [6]. Congenital heart defects are the most common malformations in children (1 % of live births) and the leading cause of infant mortality (13 %) [6,7]. Medical treatment is initiated from birth, either preceding reparative cardiac surgery or as a temporary measure in cases of ventricular septal defect expected to close spontaneously over time [7,8]. Other indications for spironolactone used in pediatric population include edematous conditions such as ascites, and nephrotic syndrome [4].

To address the unmet clinical need for accurate pediatric dosing of spironolactone, the Compounding Pharmacy of Toulouse University Hospital initially prepared oral capsules (usually from 2.5 mg to 10 mg). Given the limitations of solid dosage forms in young children, a liquid formulation was later developed using a commercial suspending vehicle. Commercial vehicles are widely used in pediatric compounding, with 63 % of pharmacists reporting their use worldwide, particularly in hospital settings (68 %) [9]. In line with this practice, a 5 mg/mL oral suspension of spironolactone was formulated using InOrpha® (INRESA, France). This ready-to-use, alcohol-free, sugar-free vehicle was selected in agreement with pediatric and neonatal teams for its safety and acceptability in this population. Manufacturer data for the 5 mg/mL spironolactone oral suspension formulated in InOrpha® reported a chemical, physical, and microbiological stability of four months at room temperature before opening, and one month after opening [10]. However, due to the poor water solubility of spironolactone [11], the formulation was subject to sedimentation with formation of a compact cake at the bottom of the bottle, compromising dose homogeneity upon administration [12]. An internal quality improvement initiative revealed that despite clear labeling and oral instructions to shake vigorously for two minutes prior to each dose, high inter-dose variability persisted [12].

The aim of this study was therefore to optimize the formulation of spironolactone oral suspension by improving its physical stability while preserving its chemical and microbiological stability. The new formulation, based on the addition of xanthan gum as a suspending agent, was assessed under real-life storage conditions in terms of homogeneity and stability [13].