Although there has been much debate about its definition among scientists, a cocrystal may be defined as a crystalline material that consists of two or more electrically neutral molecular species held together by non-covalent forces, and meanwhile all components are solids at room temperature. Obviously it is great to introduce predictable structural motifs to an active pharmaceutical ingredient (API) by design. One widely used approach to cocrystal design is based on the consideration of Delta pKa, which can represent the propensity of molecular species to form a cocrystal or a salt. In this work, p-aminobenzoic acid (PABA) was mixed with sulfamerazine (SMZ) or sulfamethazine (STH) by use of neat cogrinding and solvent-drop cogrinding. It was found that PABA and SMZ with a Delta pKa of 2.13 would form a binary eutectic, while PABA and STH with a larger Delta pKa of 2.59 can form a cocrystal in the ratio of 1:1. The phenomenon indicates that not only the Delta pKa but also the stereo-hindrance effect (geometric fit) should be considered during the design of pharmaceutical cocrystals. (C) 2011 Elsevier B.V. All rights reserved.