The results of our study of the caffeine maleic acid system have been mixed. We have failed to rediscover polymorph II of maleic acid or to grow a single crystal of the 2:1 cocrystal. On the positive side, however, we have mapped out a consistent preparative route to the 1:1 cocrystal. Study of this system has been complicated by problems brought about largely by the physical characteristics of the starting components- disparity in solubility characteristics of the pure
components and thermal decomposition of maleic acid. The metastability of the 2:1 form now seems clear, but an explanation for the appearance of maleic acid form II in the work of Day et al.18 has eluded us. We can only admire the astute and careful experimentation that brought this to light. Overall, we are left with the realization that outcomes resulting from serendipitous use of such techniques as grinding and mixed solvent crystallization are not necessarily easy to rationalize through measurement of phase behavior. This has very important implications for the transfer of state of the art laboratory chemistry into commercial practice since if we cannot, through thermodynamic measurements, map out possible process temperatures and compositions then we have serious problems.