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.
Highlights
Major depressive disorders (MDDs) are common mental disorders diagnosed in most age groups and all world regions [1]
The formulation of Paroxetine hydrochloride (PHH)-EC-SLTs was optimized by factorial design tests and single factor experiments
Producing reproducibility and stability of PHH-EC-SLTs were explored through comparing the release behaviors in vitro
Summary
Major depressive disorders (MDDs) are common mental disorders diagnosed in most age groups and all world regions [1]. The total number of patients with depression increased by 18.4% between 2005 and 2015 [2], and was estimated to exceed 300 million in 2015 [3]. MDD was ranked by WHO as one of the largest contributors to global disability (7.5% in 2015). It was one of the major contributors to suicide deaths, whose number was close to 800,000 per year [3]. Antidepressant administration was considered as an important treatment [4]. Paroxetine hydrochloride (PHH) is the most potent antidepressant approved for the treatment of MDD [5]. It has the highest affinity towards the serotonin reuptake inhibitors with a binding affinity of 0.10 nmol/L, and virtually no affinity for other receptors like histaminic, α- or β-adrenoceptor, dopaminergic or serotonergic receptors [6,7], which mPheaarmnasceuatimcs 2i0l1d8,s1i0d, xeFeOfRfePEcEt.R REVIEW
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
