Multicomponent compounds have attracted attention from the pharmaceutical industry in recent years because of the role of carriers as solubilizers and stabilizers for poorly soluble drug molecules. Mefenamic acid, (MF) is a non-steroid drug with strong analgetic, antipyretic and anti-inflammatory properties. The very low aqueous solubility of MF causes undesirable side effects when administrated orally. These effects can be reduced by increasing the drug solubility via complexation with the suitable carrier. Only one such example for MF (with β-CD) is known so far1, which reveals that although the inclusion complex is rather weak, the solubility and stability increase. It encouraged us within our ongoing efforts toward the crystal engineering of new multicomponent pharmaceutical solids to explore supramolecular synthesis for obtaining MF complexes with tetraazamacrocycles differing by ring size, but possessing the same number of incorporated nitrogen atoms predisposed for H-bonded interactions. The X-ray structure of two organic salts, (MF)2(H2teta).2H2O (I, P-1) and (MF)2(H2cyclen).2H2O (II, C2/c), reveals doubly protonated macrocycles. All four nitrogen atoms of the macrocycle are involved in hydrogen bonding with MF and water molecules in I and only three of them exclusively with MF in II. In I, H-bonding patterns are of the type R5 3(8), R4 4(12), R5 3(8), which combine the components into corrugated chains (fig.); whereas in II, only the R4 4(12) rings remain, which are shared with R4 3(8) rings.