%0 Journal Article
%T Polymorphism of spironolactone: An unprecedented case of monotropy turning to enantiotropy with a huge difference in the melting temperatures.
%A Rietveld IB
%A Barrio M
%A Lloveras P
%A Céolin R
%A Tamarit JL
%J Int J Pharm
%V 552
%N 1
%D Dec 2018 1
%M 30266517
%F 6.51
%R 10.1016/j.ijpharm.2018.09.059
%X Spironolactone form I melts at about 70 degrees lower than form II, which is very unusual for two co-existing polymorphs. The phase relationships involving this unprecedented case of dimorphism have been investigated by constructing a topological pressure-temperature phase diagram. The transition from polymorph I to polymorph II is unambiguously exothermic while it is accompanied with an increase in the specific volume. This indicates that the dP/dT slope of the I-II equilibrium curve is negative. The convergence of the melting equilibrium lines at high pressure leads to a topological P-T diagram in which polymorph I possesses a stable phase region at high pressure. Thus, forms I and II are monotropically related at ordinary pressure and turn to an enantiotropic relationship at high pressure. Given that polymorph I is the densest form, it negates the rule of thumb that the densest form is also the most stable form at room temperature, similar to the case of paracetamol.