QUALITY BY DESIGN-BASED DEVELOPMENT AND IN-VITRO EVALUATION OF DUAL RELEASE TABLET OF ETORICOXIB & THICHOLCHICOSIDE: A NOVEL CHRONOTHERAPEUTIC APPROACH FOR ARTHRITIS PAIN MANAGEMENT

Abstract

The traditional drug delivery system is not much effective when treating chronopathological diseases like arthritis. Consequently, there is a gap in the market for a delivery system that can provide an explicit treatment following the chronopharmacology of this disorder. The present study is based on the objective to develop eudragit coated dual release bilayer tablet designed by the quality by design (QbD) and based on the chronotherapeutic approach. The dual-release tablet contained an immediate release layer of etoricoxib and a sustained release layer of thiocolchicoside. The quality target product profile (QTTP) of the formulation was established along with critical quality attributes (CQA). The optimization of the dual release layer was done using a three-level, three-factor Box-Behnken design. A total of thirteen formulations of etoricoxib (ET1-ET13) and thiocolchicoside (TH1-TH13) were developed based on the design composition of etoricoxib, sodium starch glycolate and sodium bicarbonate for the immediate release (IR) layer and thiocolchicoside, HPMC E5 LV and magnesium stearate for the sustained release (SR) layer respectively. The developed dual-release layers were compressed to form a bilayer tablet. The bilayer tablets were further coated with pH-dependent polymer Eudragit S-100 to avoid drug release in upper GIT. The initial characterization and drug-excipient interaction studies were performed initially using Infra-red (IR) spectroscopy and X-ray diffraction studies (XRD). Formulations showing good micrometric properties, disintegration and drug release were selected for final compression of bilayer tablets. Formulation ET13 showed the fastest drug release (88%) at 15 minutes and quick disintegration time (21s). The sustained release thiocolchicoside tablet layer (TH1-TH13) had a hardness that varied from 4.01 to 4.45 kg/cm2. Formulation TH12 had the highest hardness, whereas TH6 showed the lowest hardness. The sustained release layer showing 97.63% of drug release after 8 hours was selected for the compression to bilayer tablet. The developed dual-layer tablets were investigated for quality parameters like hardness, % friability, weight variation, disintegration and dissolution. A high level of patient compliance is ensured through the current design as the patient does not need to get out of bed at night to take the medication.