Conformational Polymorphism in a Non-steroidal Anti-inflammatory Drug, Mefenamic Acid

For several years, the non-steroidal anti-inflammatory drug mefenamic acid, <b>MA</b>, has been known to exist as dimorphs (<b>I</b> and <b>II</b>). We report a new metastable polymorph (<b>III</b>) of <b>MA</b> obtained during attempted co-crystallization experiments and establish its stability relationship with existing forms. At elevated temperatures <b>I</b> and <b>III</b> convert to <b>II</b>, as evident from DSC experiments. On the basis of the lattice energy calculations in conjunction with thermal analysis, the stability order is proposed to be <b>I</b> > <b>II</b> > <b>III</b> at ambient conditions, whereas at elevated temperature the order is <b>II</b> > <b>I</b> > <b>III</b>. In either condition <b>III</b> is a metastable form and hence transforms to <b>I</b> at ambient conditions and to <b>II</b> at higher temperatures. Also we report the structural studies of a DMF solvate and a cytosine complex