Development and evaluation of furosemide dry suspension formulation for the paediatric management of congenital heart disease

Background: Congenital Heart Disease (CHD) with volume overload is a common cause of pediatric heart failure, often necessitating the use of loop diuretics such as furosemide (FUR) to manage symptoms like pulmonary congestion. Despite its widespread clinical use, commercially available FUR formulations are primarily designed for adult patients (e.g., 10 mg tablets), making accurate pediatric dosing (typically 1–3 mg/kg body weight) difficult. This often leads to the preparation of extemporaneous suspensions in hospitals, which carries risks of dosing inaccuracies, microbial contamination, and treatment failure. These challenges are especially pronounced in low-resource settings, where access to proper compounding facilities is limited. A stable, pediatric-appropriate formulation of FUR is therefore urgently needed.
Broad Objective: To develop and evaluate a stable furosemide dry powder suspension formulation tailored for pediatric patients with CHD, focusing on optimizing stability, viscosity, and drug release characteristics using natural suspending agents.
Methodology: Twelve dry suspension formulations were prepared using different concentrations (0.05%, 0.1%, 0.2%, and 0.3%) of three suspending agents: xanthan gum, pectin gum, and guar gum. The formulations were evaluated based on the drug's chemical compatibility with excipients,
In vitro drug release using standard dissolution testing, Rheological behavior, focusing on flow and viscosity characteristics, pH and physical stability of reconstituted suspensions under various storage conditions and Release kinetics modelling to assess the drug release mechanism.
Results: The optimised formulation demonstrated an acceptable angle of repose between 23–25°, indicating good flowability. All trial formulations maintained moisture content below 1%, enhancing shelf stability. All suspensions displayed shear-thinning (pseudoplastic) behaviour, which is desirable for ease of administration. The pH of reconstituted formulations remained within an optimal range (6.6–6.8), ensuring drug stability and palatability.
Formulation F7, containing 0.2% pectin gum, exhibited the most promising profile: 65% cumulative drug release within 30 minutes. Visually stable without sedimentation or caking for the duration of the stability testing.
Conclusion: The study successfully developed a pediatric-appropriate dry suspension formulation of furosemide that addresses the limitations of existing adult formulations. Formulation F7, containing 0.2% pectin gum, was identified as the optimal formulation among the twelve trial batches. It met pharmacopeial standards for flowability, moisture content, pH, and drug release behavior. The formulation offers a practical and stable alternative to extemporaneous preparations, minimizing risks related to dosing inaccuracies and contamination.
Recommendations: Further, in vivo evaluation should be conducted to confirm the optimised formulation's bioavailability and therapeutic efficacy in pediatric patients. Scale-up and validation studies are recommended for potential industrial manufacturing and regulatory approval.