Formulation and Evaluation of Extended-Release Chewable Tablets of Atomoxetine for Pediatric Attention-Deficit or Hyperactivity Disorder Therapy

AbstractThe present study aimed to develop and evaluate extended-release chewable tablets ofAtomoxetine HCl using hydrophilic matrix-forming polymers to achieve prolonged drugrelease, acceptable physicochemical properties, and improved palatability. Atomoxetine HClexhibited high solubility in the investigated media, with maximum solubility of 168.45 ± 2.56mg/mL in phosphate buffer pH 1.2 and 118.36 ± 1.95 mg/mL in phosphate buffer pH 6.8. AUV spectrophotometric method developed at 270 nm demonstrated good linearity over 2–20µg/mL, with a regression coefficient (R²) of 0.9982. FTIR studies confirmed drug–excipientcompatibility without significant alteration of characteristic functional groups. Allformulations exhibited satisfactory pre-compression properties, with good flow andcompressibility. Post-compression evaluation showed acceptable tablet weight, hardness,friability, thickness, and diameter, indicating adequate mechanical strength andmanufacturing reproducibility. In vitro dissolution studies demonstrated sustainedAtomoxetine HCl release for up to 12 h, with release significantly influenced by the gradeand concentration of HPMC. Increasing polymer concentration reduced the drug release rate,while HPMC K100M exhibited greater release-retarding ability than HPMC K15M. Amongthe six formulations, F5 exhibited the most desirable release profile, with 97.48 ± 1.53% drugrelease at 12 h. F5 also showed the highest overall palatability score of 4.80 ± 0.12. Accelerated stability testing demonstrated no significant changes in tablet characteristics,drug content, or dissolution profile. Thus, F5 was identified as the optimized formulation,demonstrating controlled 12-h drug release, excellent palatability, satisfactory tabletcharacteristics, and good stability, supporting its potential for further development.