Abstract. Microencapsulation of water-soluble drugs using coacervation-phase separation method is very challenging, as these drugs partitioned into the aqueous polymeric solution, resulting in poor drug entrapment. For evaluating the effect of ovalbumin on the microencapsulation of drugs with different solubility, pseudoephedrine HCl, verapamil HCl, propranolol HCl, paracetamol, and curcuminoid were used. In addition, drug mixtures comprising of paracetamol and pseudoephedrine HCl were also studied. The morphology, encapsulation efficiency, particle size, and in vitro release profile were investigated. The results showed that the solubility of the drug determined the ratio of ovalbumin to be used for successful microencapsulation. The optimum ratios of drug, ovalbumin, and gelatin for water-soluble (pseudoephedrine HCl, verapamil HCl, and propranolol HCl), sparingly water-soluble (paracetamol), and waterinsoluble (curcuminoid) drugs were found to be 1:1:2, 2:3:5, and 1:3:4. As for the drug mixture, the optimum ratio of drug, ovalbumin, and gelatin was 2:3:5. Encapsulated particles prepared at the optimum ratios showed high yield, drug loading, entrapment efficiency, and sustained release profiles. The solubility of drug affected the particle size of the encapsulated particle. Highly soluble drugs resulted in smaller particle size. In conclusion, addition of ovalbumin circumvented the partitioning effect, leading to the successful microencapsulation of water-soluble drugs.