Abstract
Compounded oral suspensions of spironolactone are commonly used in pediatric patients with heart conditions. However, due to its poor solubility in water, spironolactone suspensions may lead to sedimentation, compromising homogeneity and dose accuracy. This study aimed to assess dose accuracy of spironolactone suspension in critical care settings.
Over one month in 2020 and 2022, samples prepared by nurses in Pediatric (PICU) and Neonatal Intensive Care Units (NICU) were collected and analysed using an HPLC/UV validated method to evaluate dose deviations from target. Educational interventions on suspension preparation were conducted between the two periods.
In 2020, only 28% (NICU) and 0% (PICU) of samples met target dose with greater variability in PICU. After educational intervention from the pharmacy teams, in 2022 improvements were observed, but underdosing and variability remained significant, reflecting ongoing challenges in suspension homogeneity.
These findings highlight the need for a more stable pediatric formulation to enhance patient safety and treatment effectiveness.
Introduction
Spironolactone plays a role of interest in pediatric medicine in the off-label treatment of heart failure associated with congenital heart disease. This condition affects a significant proportion of children (1 % of live births) and contributes substantially to infant mortality (13 %) [1]. Preceding reconstructive cardiac surgery, pediatric patients often require pharmacological intervention [2].
Despite its well-recognized clinical importance, spironolactone has long lacked a commercially available formulation specifically tailored to pediatric use [3]. Regulatory frameworks in the United States (Best Pharmaceuticals for Children Act) and Europe (Pediatric Investigation Plans) aim to address these gaps by incentivizing pediatric drug development [4]. These efforts have recently led to the European Medicines Agency (EMA) granting market authorization in 2023 for Qaialdo® 10 mg/mL, a spironolactone oral suspension designed for pediatric use [5]. However, at the time of this study, Qaialdo® was not yet available in some European countries (e.g. France). Limited access leaves healthcare providers reliant on compounded oral liquid formulations to meet pediatric needs [3,[6], [7], [8], [9], [10]].
Liquid formulations are often preferred for young children under 6 years, as they allow flexible dosing based on age and weight while simplifying administration [12,13]. However, compounded preparations face numerous challenges, including concerns related to physical and chemical stability, acceptability (e.g., palatability, dose volume), and safety (e.g., excipient unsuitable for children, high osmolality) [12,14]. Furthermore, suspensions of poorly soluble drugs like spironolactone are prone to sedimentation, requiring vigorous and extended stirring to achieve homogeneity and minimize dose inaccuracies [[14], [15], [16]].
The successful dispersion of spironolactone in a universal vehicle requires a careful evaluation, considering both the chemical properties of the drug and insights from analogous substances with similar physicochemical characteristics [16,17]. Spironolactone is a synthetic steroidal, known for its low aqueous solubility and slow dissolution rate, making it an ideal candidate for a model hydrophobic drug in the literature [18]. Past attempts to create spironolactone formulations have revealed challenges, as evidenced by Nahata et al.’s 1993 study, which presented a formulation of spironolactone at 5 mg/ml in a mixture of carboxymethylcellulose simple syrup and purified water [19]. Variability in measured concentrations and laboratory conditions (ranging from 99.5 % to 113.4 %) was attributed to non– uniform dispersion of drug particles within the suspension [19].
In light of these considerations, our study seeks to evaluate the accuracy of the theoretical doses administered from a compounded oral suspension of spironolactone dosed at 5 mg/ml in two pediatric care units.
Read more here
Desquines Roxanne, Gallissot Romain, Viard Caroline, Metsu David, Ramjaun Zoubeir, Jurado Camille, Evaluating dosing accuracy and galenic dispersion quality in Hospital-Based pediatric spironolactone oral suspension, European Journal of Pharmaceutics and Biopharmaceutics, 2025, 114741, ISSN 0939-6411, https://doi.org/10.1016/j.ejpb.2025.114741.
Read also our introduction article on Orally Disintegrating Tablets (ODTs) here:
