The present invention may include a production process for a preparation containing univesicular liposomes that encapsulate a highly water-soluble drug (d) having a water solubility of higher than 10 mg/mL and have a volume-average particle diameter of 50 to 200 nm utilizing a two-step emulsification method, to enhance an encapsulation ratio of the highly water-soluble drug in the liposomes produced, as compared with the conventional one. In a primary emulsification step of the two-step emulsification method, a W1/O emulsion may be prepared by the use of an aqueous phase liquid (W1) in which the highly water-soluble drug (d) and a solubilizing aid (s) having log D of not more than −1 at pH 7.4 are dissolved in an aqueous solvent (w1).