A method of taste-masking using a spray-congealing technique was developed. Clarithromycin (CAM), a macloride antibiotic with a bitter taste, was selected as the model compound. The fundamental objective was to prevent the preparation from dissolving in the mouth, while ensuring that rapid release of CAM from the preparation could be attained in the gastrointestinal tract, resulting in bioequivalence to the conventional dosage form. Glyceryl monostearate (GM) and aminoalkyl methacrylate copolymer E (AMCE) were selected as ingredients, since GM, a substance with a low melting point, is able to be decomposed by an enzymatic reaction in the intestinal tract where the solubility of AMCE is very low. On the other hand, AMCE was selected because it is freely soluble at low pH levels (e.g. the pH level in the stomach), but insoluble in neutral and high pH levels (e.g. the pH level in the mouth).Spherical particles of the matrix (spherical matrix) and disks of matrix with various ratios were prepared, and the optimum ratios of CAM, GM and AMCE for the following release criterion were determined by experimental design (the simplex method). That is, 100 mg/l of CAM in the spherical matrix should be completely released within 20 min in pH 4.0, and less than 14 mg/l of CAM in spherical matrix should be released at 60 min in pH 6.5.As a result, the optimum formula for the matrix in consistency with the criterion was 3 : 6 : 1 for CAM, GM and AMCE, respectively.