Polymorphic Transitions of Erlotinib Hydrochloride in PLGA Binary Mixtures: Influence of Polymer Functionality and Method of Crystallisation.

Erlotinib hydrochloride (ERL), an oral tyrosine kinase inhibitor used in non-small cell lung cancer, is a classic example of drug polymorphism. However, the influence of crystallisation methods, PLGA, and thermal ageing on its polymorphic behaviour remains unexplored. This study investigated ERL polymorphism in binary mixtures prepared by blending, co-grinding, and solvent evaporation. PXRD revealed that blending and co-grinding retained ERL polymorphic form A, whereas solvent evaporation yielded form B in all binary mixtures. Thermal ageing has a significant effect on ERL crystallinity. DSC melting endotherms for form A are at 213.75 and 233.26°C, whereas form B shows a single melting endotherm at 231.96°C. MDSC efficiently captured the melt-mediated recrystallisation of form A. Further, ATR-FTIR with chemometric analysis differentiated the polymorphs into form A (anti) and form B (syn) conformations based on spectral regions at 3270 cm⁻1 (non-classical H-bonding) and 2540 cm⁻1 (N⁺-H···Cl⁻ interactions). SEM revealed plate-like and needle-like morphologies for forms A and B, respectively. Conversely, saturation solubility results reported higher solubility for the solvent-evaporated drug, due to its crystal morphology. Drug content by RP-HPLC (98-102% w/w) confirmed that the observed changes were solely physical transitions. Overall, this study provides insights into the development of ERL-loaded PLGA microspheres.