Hydrates are ubiquitous multicomponent
solids of particular interest in the pharmaceutical field. As
such, there is a practical need of monitoring the stability of
this class of solids, especially when formulated with one or
more excipients. In this paper, we propose an innovative solid
state method, namely, polymer-assisted grinding (POLAG),
for exploring the stability of carbamazepine dihydrate under
the simultaneous effects of manufacturing-induced stress
(milling) and the presence of polymeric excipients. We
demonstrate that, while milling alone did not cause any dehydration, the presence of specific polymers induced partial or total
dehydration of the selected model drug carbamazepine dihydrate. Through detailed experimental evidence, it is concluded that
the polymer chain length plays a main role in the kinetics of the solid state reaction, while a combination of the amount of
polymer and the milling time allowed the isolation of different polymorphic forms of the resulting dehydrated carbamazepine
solid. Additional POLAG experiments suggested that polymers of a high molecular weight are less likely to cause dehydration
due to their lower affinity for water. POLAG may therefore be used both as a screening method for determining the dehydration
propensity of a specific hydrated form in the presence of polymers and for isolating highly metastable forms of the resulting
anhydrous product.
