DEVELOPMENT AND CHARACTERIZATION OF SOLID DISPERSIONS OF SERTRALINE HYDROCHLORIDE FOR IMPROVED DISSOLUTION PERFORMANCE

Mohammad Taleb Hossain, Md. Mufakkarul Islam, Mohammad Sofi, Ruminoman Dipu, Md. Harun Ar Rashid, Mohammad Anisur Rahman Uzzal, Md. Sahab Uddin*

ABSTRACT

Sertraline hydrochloride (HCl) is a widely prescribed selective serotonin reuptake inhibitor (SSRI) characterized by poor aqueous solubility, that severely limits its oral bioavailability. This study is designed to increase the dissolution rate of sertraline HCl through solid dispersion formulations using hydrophilic polymeric carriers. Using a design of experiments (DOE) approach, nine solid dispersions were made using the solvent evaporation method at a 1:3 drug-to-carrier ratio. Formulations combined sertraline HCl (100 mg) with varying proportions of hydroxypropyl cellulose (HPC), polyethylene glycol 6000 (PEG 6000), polyvinylpyrrolidone K90 (PVP K90), and sodium lauryl sulfate (SLS). In vitro dissolution profiles were assessed in standard phosphate buffer (pH 6.8) using a USP Type II apparatus. All solid dispersions demonstrated significantly improved dissolution efficiency compared to pure sertraline HCl (60.92 ± 1.13% at 60 min). Formulation F7 (containing 65% HPC, 30% PEG 6000, and 5% PVP K90) emerged as optimal, achieving 95.38 ± 0.70% drug release at 60 minutes—representing a 56.56% relative improvement. F7 exhibited superior dissolution efficiency (61.96 ± 0.81%), remarkable reproducibility (RSD = 1.51%), and rapid initial kinetics. One-way ANOVA confirmed highly significant variations in drug release across formulations during early time intervals ($p < 0.001$), with profiles converging toward the 60-minute endpoint ($p = 0.626$). Pearson correlation analysis verified HPC as the primary performance-determining carrier ($r = +0.695, p = 0.038$). These findings demonstrate that solid dispersion strategies using optimized polymeric balances offer a robust and highly reproducible methodology for accelerating the dissolution profiles of BCS Class II antidepressants.

Keywords: Sertraline hydrochloride, solid dispersions, dissolution enhancement, hydrophilic carriers, design of experiments.