Understanding of solid–liquid
equilibria for polymorphic
systems is crucial for rational design and efficient operation of
crystallization processes. In this work, we present a framework to
determine the temperature dependent solubility based on experimentally
accessible thermodynamic data measured at a single temperature. Using
this approach, we investigate aqueous solubility of α, β,
and γ-glycine, which, despite numerous studies, have considerable
quantitative uncertainty, in particular for the most stable (γ)
and the least stable (β) solid forms. We benchmark our framework
on α-glycine giving predictions in excellent agreement with
direct solubility measurements between 273–340 K, using only
thermodynamic data measured at the reference temperature (298.15 K).
We analyze the sensitivity of solubility predictions with respect
to underlying measurement uncertainty, as well as the excess Gibbs
free energy models used to derive required thermodynamic quantities
before providing solubility predictions for β and γ-glycine
between 273–310 and 273–330 K, respectively. Crucially,
this approach to predict solubility as a function of temperature does
not rely on measurement of solute melting properties which will be
particularly useful for compounds that undergo thermal decomposition
or polymorph transition prior to melting.