The congealable disperse phase method for preparing sustained release microspheres involves an emulsification process using water as the external phase and molten hydrophobic wax as the disperse phase into which the drug is loaded. Attempts to entrap highly water-soluble drugs using this process have often resulted in low loading efficiency as the drugs partition into the external water phase during emulsification and are lost. A novel method employing salts and wetting agents was developed to improve the loading efficiency of the highly water-soluble drug, guaifenesin, using this method. The drug/wax ratio (D/W) and the presence of salts and wetting agents greatly influenced microsphere properties. To optimize the process for drug loading efficiency and release rate, three different D/Ws, salts and wetting agents were chosen and a full 3 3 factorial design experiment was performed. Any significant differences among the levels of the variables and their individual and joint effects on entrapment efficiency and T-50 (time for 50% drug release) were determined. Entrapment efficiencies in the range 35.1-86.3% were obtained for the various factor-level combinations of the variables. Particle size was in the range 140-385 mum and T-50 was 0.59-2.72 h for the microspheres obtained. The D/W and type of salt used significantly affected drug entrapment and T-50, while the nature of wetting agent was not significant at p < 0.05. The microspheres prepared using 1: 4 D/W showed the highest entrapment efficiency and slowest drug release.