Polymorphs and Cocrystals: A Comparative Analysis

Abstract

Controlling polymorphism has been the subject of vigorous
research in the recent past in the pharmaceutical industry due to the
distinct physicochemical properties associated with each solid form.
Developing cocrystals/salts of active pharmaceutical ingredients (APIs)
has gained tremendous research interest in recent years owing to their
potential to improve pharmaceutically relevant properties without affecting
therapeutic efficacy. It is observed that compounds that exhibit polymorphism
and also contain several H bond donor/acceptor groups have
a tendency to form cocrystals and sometime even display cocrystal polymorphism, although this tendency cannot be generalized. The aim of this
contribution is to correlate crystal structures of some polymorphic APIs
and their respective cocrystals to understand the rationale behind a polymorphic
compound generating cocrystals. Here, we make an attempt
to compare how the conformation of the molecule observed in its polymorphs
support the generation of cocrystals/salts. We understand that it
is impossible to cover all the polymorphs and their cocrystals/salts available
in the CSD; the comparative study has been carried out with a few
case studies, wherein APIs displayed polymorphism (conformation) and
also formed cocrystals/salts.