A focus on chasing pharmaceutical polyamorphs to design better oral drug formulations.

Abstract

The pharmaceutical industry cares about reducing toxic side effects of drugs in oral formulation. The best solution is to reduce the drug dose. To do so, drugs are required to have high aqueous solubility to ensure good bioavailability. Amorphous drugs are much more water soluble than their crystalline counterparts, but can lack physical stability. Martins and Rades, et al. (I. C. B. Martins and T. Rades et al., Chem. Sci., 2023, 14, 11447-11455, DOI: https://doi.org/10.1039/D3SC02802J) demonstrate for the first time that polyamorphs (amorphous polymorphs) of drugs are now a reality. They demonstrated proof-of-concept, reproducible preparation methods for 3 polyamorphs (I, II and III) of hydrochlorothiazide (HCT) that display different glass transitions temperatures (T g) and distinct structural relaxation profiles as excellent analytical indicators for discriminating between the polyamorphs. HCT polyamorph-II displayed improved physical stability with respect to the other HCT polyamorphs. A tangible benefit of polyamorphism research is the opportunity to select a specific polyamorph of a drug with the desired solubility and physical stability to be incorporated in an oral formulation, a strategy that should improve drug effectiveness.