An up-to-date approach to drug polymorphism

Topological rules for constructing (p,T) diagrams of drug polymorphs are di scussed following a classical approach founded upon the Ostwald's principle of least vapor pressure. This method allows the definition of hierarchy st abilities among the crystal varieties of a polymorph as a function of tempe rature and pressure, it has been applied to two trimorphic drugs. sulfanila mide and piracetam. The overall monotropy of the metastable orthorhombic al pha-variety of sulfanilamide was demonstrated. in fact, it cannot possess a ny stability region, even at high pressures. The method for piracetam showe d a sensitivity to the set of experimented data to which it is applied. Dep ending on the values of the transition temperatures of forms II (triclinic) and III (monoclinic) to form I(monoclinic), three kinds of (p.T) represent ations were derived. Preliminary applications of a high-pressure piezotherm al method did not discern the three different kinds of (p.T) diagrams. (C) 1998 Elsevier Science B.V.