Metastability and instability of organic crystalline substances.
Discovery of an unexpected and thermodynamically paradoxical transition from a crystalline state to an amorphous dense glassy state induced in pure organic substances by a direct absorption of a quantity of heat under atmospheric pressure and its detailed analysis performed with the use of a sensitive scanning transitiometer are described. The obtained results present first experimental precise evidence for understanding the mechanism of such a structural instability of crystalline substances in the form of c-a transition. The observed c-a transition is a purely physical phenomenon, occurring between two nonequilibrium states, a metastable crystalline phase and a dense glass, occurring through a local transient phenomenon of virtual melting. The metastable state of a crystalline substance can be caused by existence of a number of crystalline imperfections created either during crystallization or by external actions. By measuring extremely sensitive energetic effects, we found the present method to be helpful for quantitative determination of the critical number of imperfections in a crystalline solid, which make it metastable and for an indication under which conditions such a metastable crystalline form becomes unstable. By performing the transitiometric analysis of c-a transitions with two polymorphs of rosiglitazone maleate, we demonstrated to what extent this analysis is important in investigation of stability of crystalline components of drugs.
Randzio
Stanislaw L
SL
Polish Academy of Sciences, Institute of Physical Chemistry, Kasprzaka 44/52, 01-224 Warszawa, Poland. randzio@ichf.edu.pl
Kutner
Andrzej
A
D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D007004:Hypoglycemic Agents / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009930:Organic Chemicals / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011108:Polymers; D000077154:Rosiglitazone; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D045162:Thiazolidinediones / Q000737:chemistry; D014961:X-Ray Diffraction
D007004:Hypoglycemic Agents; D009930:Organic Chemicals; D004364:Pharmaceutical Preparations; D011108:Polymers; D045162:Thiazolidinediones; D000077154:Rosiglitazone