Development of an Optimized Formula of Pomegranate Peel Extract Dispersible Tablet and Its Antidepressant Evaluation

Depression is a multifactorial disorder in which neuroinflammation—driven by chronic microglial and astrocyte activation—is recognized as an important mechanism that complements, rather than displaces, the classical monoamine hypothesis, dysregulating the monoaminergic systems that govern mood. Pomegranate (Punica granatum L.) peel polyphenols—notably punicalagin and ellagic acid—exert antidepressant-like effects principally by modulating the serotonergic and adrenergic systems and restoring stress-depleted brain monoamines, with anti-neuroinflammatory and antioxidant activity as a secondary contributor. This study developed and optimized a pomegranate peel extract dispersible tablet, validating retention of its in vivo antidepressant activity. Tablets were prepared by direct compression and optimized via a two-factor factorial design varying croscarmellose sodium (superdisintegrant) and polyvinylpyrrolidone K-30 (binder). The optimized tablet (equivalent to 100 mg/kg extract) was assessed in male BALB/c mice by the tail suspension and forced swim tests against unformulated extract and fluoxetine (20 mg/kg). The optimal formulation (11.68% croscarmellose sodium, 2.02% polyvinylpyrrolidone K-30) showed good physical quality (disintegration 87 s, friability 0.28%, hardness 6.58 kp). In both tests it significantly reduced immobility time (p < 0.05), with no significant difference from the extract or fluoxetine (p > 0.05). The dispersible tablet retained efficacy, supporting its potential as a preclinical nutraceutical candidate for depression.