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The aim of this study was to develop a depot formulation of mirtazapine by w/o emulsification method using chitosan as controlled release biodegradable polymer. Chitosan microspheres are used to provide controlled release of mirtazapine and to improve the bioavailability of degradable substances or enhance the uptake of hydrophilic substances across the epithelial layers. The effect of various parameters, such as stirring rate, drug to chitosan ratio, chitosan concentration and glutaraldehyde concentration on entrapment efficiency and release study was studied. Stirring speed affects the size of microspheres, drug to chitosan ratio and chitosan concentration affects the entrapment efficiency and release study; glutaraldehyde concentration affects the release of the drug molecule from the microspheres.