Development of an enteric-coated sustained-release powder for oral suspension of paroxetine Based on cation exchange resin

Paroxetine (PX) is a first-line selective serotonin reuptake inhibitor (SSRI) for major depressive disorder. Currently, the enteric-coated sustained-release tablet represents the dominant clinical standard due to its ability to mitigate gastric irritation and ensure sustained release in the intestine to reduce adverse effects. However, these tablets must be swallowed intact, making them unsuitable for patients with dysphagia; manipulation (e.g. crushing or chewing) destroys the functional coating, leading to dose dumping and unpredictable systemic exposure. To address these critical therapeutic gaps, this study developed a novel reconstitutable enteric-coated sustained-release powder using ion-exchange resin technology for oral suspension of PX. PX was loaded onto Amberlite® IRP88 and subsequently coated with cellulose acetate phthalate via fluidized-bed processing to inhibit gastric release while enabling prolonged release in the intestine. The optimized formulation (PX@CM) demonstrated high drug entrapment efficiency and a robust zero-order release profile in simulated intestinal fluid. In vivo pharmacokinetic studies in rats confirmed its potential clinical advantages: compared to commercial immediate-release (IR) oral tablets, the suspension significantly lowered Cmax (0.24 vs. 0.44 μg/mL) and prolonged Tmax (6.67 vs. 4.00 h). These pharmacokinetic improvements provide a ‘peak-blunting’ effect that suggests a potential to minimize concentration-dependent side effects. Consequently, this formulation emerges as a promising, patient-centric alternative for vulnerable populations requiring long-term antidepressant therapy.