Development of a Pre‑Measured Furosemide Oral Granules Kit for Paediatric Heart Failure in Sub‑Saharan Africa Using a Quality‑by‑Design Approach

Introduction: In Sub‑Saharan Africa, paediatric heart failure therapy often relies on manual compounding of adult furosemide tablets, which may introduce dosing inaccuracies and stability concerns from aqueous hydrolysis and photodegradation in tropical climates. This study aimed to develop a pre‑dosed furosemide oral granules kit using Quality‑by‑Design (QbD) to achieve content uniformity, chemical stability, and predictable reconstitution, supporting accurate dosing without cold‑chain requirements.

Methodology: Pre‑formulation studies and risk assessment (Ishikawa/FMEA) identified critical quality attributes, content uniformity, dissolution, and stability. A wet‑granulation prototype (FOG‑01) was optimised. Flow properties, moisture content, dispersion time, reconstitution time, and homogeneity were evaluated against predefined criteria. Accelerated stability was assessed over 4 weeks (40 °C ± 2 °C) and in‑use stability of the reconstituted suspension at 25–30 °C and 2–8 °C under controlled laboratory conditions.

Results: Optimised granules exhibited good flow (Carr’s index 17.5%), rapid dispersion (53 s), and homogeneity (USP acceptance value 4.8). Four‑week accelerated stability showed 96.8% potency, 0.58% total impurities (limits 90–110%, ≤5%), and dissolution ≥89.5% at 15 min (≥80%). Reconstituted suspension potency remained acceptable for 7 days at room temperature and 14 days refrigerated. Preliminary lab‑scale cost was estimated at USD 3.00–4.00 per kit.

Conclusions: The QbD‑derived granule kit met the predefined quality targets, providing a potential alternative to manual compounding. Key limitations include evaluation of a single batch, short‑term accelerated stability, and laboratory‑based in‑use testing; long‑term real‑time stability in Zone IVb, multi‑batch validation, clinical studies, and caregiver usability assessments are necessary before widespread implementation. The preliminary cost projection requires manufacturing‑scale verification.