a process for preparing microspheres using very cold temperatures to freeze polymer - biologically active agent mixtures into polymeric microspheres with very high retention of biological activity and material . polymer is dissolved in a solvent together with an active agent that can be either dissolved in the solvent or dispersed in the solvent in the form of microparticles . the polymer / active agent mixture is atomized into a vessel containing a liquid non - solvent , alone or frozen and overlayed with a liquified gas , at a temperature below the freezing point of the polymer / active agent solution . the cold liquified gas or liquid immediately freezes the polymer droplets . as the droplets and non - solvent for the polymer is warmed , the solvent in the droplets thaws and is extracted into the non - solvent , resulting in hardened microspheres .