New drug delivery systems offer numerous advantages compared to the conventional dosage forms such as modified release of active substance (Freitas et al., 2005, Freiberg et al., 2004), protection of encapsulated materials against oxidation and humidity (especially important for hygroscopic drugs), masking of undesirable odor or taste of active ingredient (Silva et al., 1999), improved efficacy, as well as improved patient compliance and convenience (Berchane et al. 2007). Microencapsulation of highly-water soluble drugs is a challenge especially if low molecular weight component must be encapsulated. The high hygroscopicity of the currently produced cardioprotective drug mildronate (3-(2,2,2- trimethylhydrazinium)propionate dihydrate) defines additional requirements to both the packaging material and the storage conditions that is why up to now only conventional dosage forms of mildronate – capsules and sterile solution – are manufactured. Taking into account growing interest in prolonged administration of mildronate an attempt was made to prepare modified release form of the drug. An appropriate selection of the polymer matrix is necessary in order to develop successful drug delivery system. In the present study polylactide (PLA), polystyrene (PS) and polyhydroxybutyrte (PHB) were tested for controlled delivery of highlywater soluble mildronate. The effect of polymer choice on the final product was investigated and release rate of active component from microparticles was evaluated.