The present study involves preparation and evaluation of floating microspheres with cimetidine as model drug for prolongation of gastric residence time. The microspheres were prepared by the solvent evaporation method using polymers hydroxypropylmethyl cellulose and ethyl cellulose. The shape and surface morphology of prepared microspheres were characterized by optical and scanning electron microscopy, respectively. In vitro drug release studies were performed and drug release kinetics was evaluated using the linear regression method. Effects of stirring rate during preparation, polymer concentration, solvent composition and dissolution medium on the size of microspheres and drug release were also observed. The prepared microspheres exhibited prolonged drug release (~ 8 h) and remained buoyant for > 10 h. The mean particle size increased and drug release rate increased at higher polymer concentration. In vitro studies demonstrated diffusion-controlled drug release from the microspheres. No significant effect of the stirring rate during preparation on drug release was observed.U radu je opisana priprava i evaluacija plutajućih mikrosfera za produljeno zadržavanje u želucu. Cimetidin je izabran kao model lijeka. Mikrosfere su pripravljene metodom uparavanja otapala koristeći hidroksipropilmetilcelulozu i etilcelulozu. Optičkom, odnosno pretražnom elektronskom mikroskopijom karakterizirani su oblik i morfologija površine mikrosfera. Kinetika oslobađanja ljekovite tvari in vitro evaluirana je pomoću metode linearne regresije. Proučavan je utjecaj brzine miješanja tijekom priprave, koncentracije polimera, vrste otapala i medija za oslobađanje na veličinu mikrosfera, odnosno oslobađanje lijeka. Iz pripravljenih mikrosfera lijek se produljeno oslobađa (~ 8 h), a mikrosfere ostaju plutati više od 10 h. Veće mikrosfere dobivene su upotrebom veće koncentracije polimera. Pokusi in vitro ukazuju da je oslobađanje ljekovite tvari studies kontrolirano difuzijom. Brzina miješanja tijekom priprave nema utjecaja na oslobađanje ljekovite tvari