Cocrystals of carbamazepine with nicotinamide and saccharin are shown to be polymorphic. Two polymorphs of carbamazepine-nicotinamide (CBZ-NCT) cocrystals and two polymorphs of carbamazepine-saccharin (CBZ-SAC) cocrystals were grown from solution in the presence of polymer heteronuclei. The two CBZ-NCT polymorphs, CBZ-NCT I and a polymer nucleated (PN) form of CBZ-NCT, were characterized by Raman spectroscopy and powder X-ray diffraction. CBZ-SAC II, a new polymorph, was found to be in the monoclinic space group C2/c with a = 35.72 Å, b = 6.84 Å, c = 16.11 Å, and β = 98.03°. The unique feature of CBZ-SAC II is the formation of a heterosynthon between the carbamazepine and saccharin. These results are notable because CBZ-NCT and CBZ-SAC are among the most widely studied pharmaceutical cocrystals.Cocystallization has recently been rediscovered as a powerful technique to modify key solidstate properties of pharmaceuticals such as solubility, stability, and dissolution rate. 1,2 From a supramolecular standpoint it is pleasing to see that predictable structural motifs can be introduced by design, offering at least a partial solution to the problem of controlling crystal structure. This element of predictability may be misinterpreted as leading to the formation of a single structure and therefore a lack of crystal polymorphism. Here we investigate this issue for two cocrystals of the highly polymorphic pharmaceutical carbamazepine. 3The crystallization properties of carbamazepine-nicotinamide (CBZ-NCT) have been thoroughly investigated 4-7 and the generation of CBZ-NCT cocrystals has been achieved through solution crystal growth, 4,5 slurry conversion, 6 and melt crystallization. 7 From these studies one form of CBZ-NCT cocrystal has been thoroughly characterized and its structure elucidated by single crystal X-ray diffraction. 4 Crystal growth from the melt results in a second form of CBZ-NCT that is metastable. 7Our study of CBZ-NCT cocrystals utilized functionalized cross-linked polymers as heteronuclei for crystal growth, 8 a strategy that has previously demonstrated effectiveness in polymorph discovery of pharmaceuticals, 8,9 extended solids, 10 and inorganic complexes. 11 Cocrystals were grown by evaporation of ethanol solutions containing a stoichiometric ratio of carbamazepine and nicotinamide contacting 96 individual polymers in a polymer library. Three separate polymer libraries were utilized derived from monomers with non-polar and aromatic functional groups, polar nitrogen rich functional groups, and polar acidic functional groups (see Supporting Information). Optical microscopy of the resulting crystals revealed needle-like morphologies with no readily distinguishable features. Raman spectroscopy of the crystals identified several crystalline forms including carbamazepine, nicotinamide, CBZ-NCT I, and a cocrystal with a Raman spectrum indistinguishable from that reported for CBZ-NCT II. 7 Powder X-ray diffraction (PXRD, Figure 1) of CBZ-NCT I is in accord with the previously reported powder patter...