Paradoxical effect of coating on natural guar gum blended carbomer matrix systems for the neurological depressive disorders

Abstract

Oral extended release products offer potential advantages in patient compliance and therapeutic outcomes like sustained blood levels with attenuation of adverse effects. In neuropsychiatric disorders like depression, most of the formulations serve a marketing objective rather than a clinical objective. The present investigation was aimed to develop a once daily sustained release formulation for delivery of an acid-labile, water soluble antidepressant, duloxetine HCl. The formulation was pragmatically designed using blend of natural and synthetic polymeric biomaterials that it releases the drug at alkaline pH in a sustained manner. The basic intention was to develop a tablet formulation with hydrophilic matrix core, using blend of release retarding natural biodegradable polymers such as guar gum, carbopol 71G-NF (a synthetic carbomer) and C-Pharm® gel. Barrier coating using HPMC-E5 was given to retard the initial release followed by enteric coating with HPMC-AS to prevent exposure of drug in acidic mileau of the stomach. The formulation exhibited desired release pattern and was described best-fit by Hixon-Crowell model. Stability analysis under stress conditions up to one month displayed good reproducibility. The matrix tablets successfully decreased the symptoms of depression (significant decrease in immobility time) in a rat forced swimming model. Pharmacokinetic data of the formulation revealed (tmax ~ 6 h, Cmax ~ 1157.58 ng/ml, mean AUCt~11145.04 ng*h/ml, and Ka~1.07h-1) good correlation in all animals. Keywords: Matrix tablets; Duloxetine HCl; Sustained release; Enteric coating; Hixon-crowell model