Development And Optimization Of Amoxicillin Trihydrate Minitablets As A Stable And Pediatric-Friendly Alternative To Oral Suspension

Abstract

Amoxicillin trihydrate, a widely prescribed β-lactam antibiotic, exhibits hydrolytic instability in aqueous environments, posing stability limitations in conventional powder-for-oral-suspension dosage forms. The present study aimed to develop a stable, mechanically robust, and palatable minitablet formulation of amoxicillin as a dose-flexible alternative for pediatric use. A systematic phase-wise optimization approach was employed to evaluate direct compression, dry granulation, and wet granulation techniques. Wet granulation was identified as the most suitable manufacturing process for high drug loading, providing improved compressibility and mechanical integrity. Subsequent optimization of filler composition, disintegrant distribution and excipient balance resulted in minitablets exhibiting rapid disintegration and satisfactory dissolution performance. The optimized formulation demonstrated friability of 0.36%, disintegration time of 50 seconds, and approximately 90% drug release within 15 minutes. Sensory evaluation confirmed statistically improved palatability following combined sweetener and flavor optimization. Stability studies conducted under ICH-recommended accelerated and long-term conditions showed minimal degradation, maintained assay within 95–105%, and total impurities below pharmacopoeial limits over six months. Solid-state characterization by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD) confirmed that the crystalline trihydrate form of amoxicillin was retained in the optimized batch following wet granulation. The developed minitablet formulation provides a stable, dose-flexible, and pediatric-compliant alternative to conventional oral suspension, addressing key limitations related to hydrolytic instability, dosing variability, and in-use shelf-life.