Development of Paroxetine Hydrochloride Single Layer Controlled-Release Tablets Based on 3² Factorial Design

Abstract

Major depressive disorder (MDD) is one of the main contributors to disability and suicide mortality globally. Paroxetine hydrochloride (PHH) is the most potent antidepressant used for MDD treatment. Due to its reduced side effects PAXIL® CR is a widely-used controlled-release formulation of PHH. However, the complicated double-layer production of PAXIL® CR faces the risk of layer separation. In this study, PHH enteric coating single layer controlled-release tablets (PHH-EC-SLTs) were designed as a simplified substitution of PAXIL® CR through a rational formulation screening. The optimized PHH-EC-SLTs showed similar release behaviors in vitro to PAXIL® CR and the release profiles corresponded to a zero-order release model (R2 = 0.9958). Polymer matrix erosion was the main release mechanism, according to the fitting exponents n > 1 in the Korsmeyer-Pappas model. Crucial pharmacokinetic parameters including peak-reaching time (Tmax), peak concentration (Cmax) and the area under the blood level-time curve (AUC0-48) of PHH-EC-SLTs and PAXIL® CR had no significant difference (p > 0.05) and the relative bioavailability (F = 97.97%) of PHH-EC-SLTs demonstrated their similar pharmacokinetic profiles in vivo. In view of avoiding layer separation risk and simplifying the preparation processing, the self-made PHH-EC-SLTs could be considered as a safe and economic alternative to PAXIL® CR.

Keywords

• depressive disorder
• paroxetine hydrochloride
• factorial design
• single layer controlled-release tablet
• PAXIL^® CR
• oral bioavailability