Commonly, the microencapsulation of a lipophilic drug in pH-sensitive polymeric matrix via an ordinary oil/oil emulsification allows for entrapping limited drug amounts due to its loss into the external phase. Here, we propose a microencapsulation method on the basis of an oil/water emulsification method using n-butanol. Eudragit® S100 microspheres were prepared by an oil/water emulsification solvent extraction method trapping ibuprofen as lipophilic model drug. Morphological analyses of the obtained particles showed a spherical shape and a sponge-like internal structure. In order to increase the entrapment efficacy several preparation parameters were optimized, such as theoretical drug load and surfactant concentration in the external phase. The particle size varied slightly around 170 μm, barely influenced by the modified process parameters. Drug leakage at pHs below the polymer dissolution pH was highest with microspheres prepared at low theoretical drug loading and low surfactant concentrations. In vitro drug release was found to be strongly pH-dependent; ibuprofen was retained in microspheres at pH 2.0 (<20% release within 4 h) whereas a higher leakage was observed at pH 5.5 and a nearly immediate drug release was obtained at pH 7.4. The use of n-butanol was found to be a new promising alternative for the preparation of pH-sensitive microspheres by an oil/water emulsification.