What experimental conditions or methods can be employed to induce the formation of multiple polymorphs in a cocrystal that previously exhibited various polymorphs with a specific solvent under ambient conditions, but now only forms a single polymorph with the same solvent and other solvents of varying polarity?
Dear Sonali,
There is no precise instruction or algorithm to "revive" metastable polymorphs. Multiple issues may be discussed, such as:
1. "Disappearing polymorphs" (this is the worst case for you - D.K. Bučar, R.W. Lancaster, J. Bernstein, Disappearing Polymorphs Revisited, Angew. Chemie Int. Ed. 54 (2015) 6972–6993. https://doi.org/10.1002/anie.201410356 )
2. Changes in temperature of crystallization or evaporation, which may be controlled using thermostat. Changes of solvent... even if it is just a new bottle or provider, etc. (A lot of information may be found in the book: H.E. Buckley, Crystal Growth, Wiley, 1951. https://books.google.ru/books?id=OzZRAAAAMAAJ )
3. Water moisture may also be a reason. It is more frequent for crystallization from melt, but may be crucial for crystallization from solvents too. (L. McGregor, D.A.D.A. Rychkov, P.L.P.L. Coster, S. Day, V.A.V.A. Drebushchak, A.F.A.F. Achkasov, G.S.G.S. Nichol, C.R.C.R. Pulham, E.V.E.V. Boldyreva, A new polymorph of metacetamol, CrystEngComm. 17 (2015) 6183–6192. https://doi.org/10.1039/C5CE00910C and V.A. Drebushchak, L. McGregor, D.A. Rychkov, Cooling rate “window” in the crystallization of metacetamol form II, J. Therm. Anal. Calorim. 127 (2017) 1807–1814. https://doi.org/10.1007/s10973-016-5954-0 )
Hope this will help,
Best wishes!
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