The discovery and investigation of a crystalline solid solution of an active pharmaceutical ingredient

Citation:
Patel, M. A., M. H. H. AbouGhaly, and K. Chadwick, "The discovery and investigation of a crystalline solid solution of an active pharmaceutical ingredient", International Journal of Pharmaceutics, vol. 532, no. 1, pp. 166 - 176, 2017.

Abstract:

Abstract Understanding the phase behavior of crystal forms is essential in drug formulation development, as physical stability of the active pharmaceutical ingredient (API) is critical to achieving the desired bioavailability. Solvents greatly impact the physical stability of crystalline solids, resulting in a variety of well-known phase transitions, such as hydrate/solvate formation. However, solvent incorporation may also result in the formation of a less-known crystalline solid solutions (CSSs). The identification and characterization of \{CSSs\} and their effect on \{API\} physicochemical properties have not been investigated. This is the first reported instance of a \{CSS\} for an API. An exhaustive study of the phase behavior of the enantiotropically related polymorphs, I and II, of Benzocaine in water and ethanol revealed that Form I formed a \{CSS\} with water below 294.5 K. Construction of the phase diagrams of Forms I and İI\} in water and ethanol revealed that \{CSS\} formation significantly decreased the phase transition temperature between Forms I and İI\} in water. This change resulted from the increased disorder in the lattice of Form I due to the presence of water. This work demonstrates the importance of understanding the formation of \{CSSs\} on the thermodynamic behavior of crystalline pharmaceutical solids.

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