Design and manufacturing of fixed-dose combination coated minitablets for pediatric GERD therapy

This study aimed to develop an innovative pediatric-friendly fixed-dose combination (FDC) of omeprazole (OMZ) and domperidone (DOM) for the treatment of gastro-esophageal reflux disease (GERD) in children. The formulation strategy focused on enteric-coated minitablets (MTs), a dosage form that poses significant technological challenges when co-formulating two APIs within the same small-sized unit, particularly with respect to powder processability, content uniformity, and manufacturability, but offers advantages in terms of dose accuracy, dosing flexibility, ease of swallowing, and acceptability. Preformulation studies (thermoanalysis, infrared spectroscopy, and hot-stage microscopy) confirmed the absence of physicochemical incompatibilities between OMZ and DOM. Due to the high drug load and the small MTs size (≈2 mm), melt granulation using Macrogol 6000 was selected to improve flowability and compactability. The manufacturing process was progressively optimized using placebo formulations and OMZ-only granules before application to the FDC system. The resulting granules were compressed into MTs containing 2 mg OMZ and 1 mg DOM per unit, consistent with pediatric dosing requirements, using a laboratory-scale eccentric press (final weight: 8.39 ± 0.26 mg). The optimized MTs were subsequently seal-coated (5% weight gain) and enteric-coated using a methacrylic acid copolymer (20% weight gain) using a laboratory-scale fluid-bed system to protect OMZ from gastric degradation and ensure intestinal drug release. Coated FDC-MTs were characterized for morphology, mass and content uniformity, mechanical strength, disintegration behavior, and dissolution performance and met the European Pharmacopoeia requirements. Overall, this proof-of-concept study demonstrates the feasibility of producing co-formulated FDC MTs as accurate, flexible, and child-appropriate dosage form addressing an unmet need in pediatric GERD. • Addresses unmet need for age-appropriate pediatric fixed-dose combinations (FDC) • Innovative pediatric FDC minitablets of omeprazole and domperidone for GERD • Minitablets enable dose flexibility and accuracy in children • Robust core MTs achieved via optimized melt granulation and compression processes • Integrated multi-step manufacturing supports scalability and Pharmacopeia compliance