Co-crystals of the antiretroviral nevirapine: crystal structures, thermal analysis and dissolution behaviour

Synthesis and physicochemical characterization of co-crystals of the antiretroviral drug nevirapine (NV) with the pharmaceutically acceptable co-formers saccharin, rac-tartaric acid, maleic acid, glutaric acid and salicylic acid are reported for the first time. The respective stoichiometric NV : co-former ratios are 2 : 1, 1 : 1, 1 : 1, 1 : 1 and 2 : 1. In the 1 : 1 co-crystals, the predicted R-2(2)(8) NV(amide)carboxylic acid supramolecular synthon occurs, whereas in the 2 : 1 species, the co-former is H-bonded to a centrosymmetric NV dimer formed via the R-2(2)(8) amide-amide synthon. Thermal analysis of three co-crystals revealed the unusual phenomenon of precipitation of NV from the melt. Co-crystallization of NV with maleic acid led to the highest (similar to fivefold) increase in the aqueous solubility of the drug.