Pharmaceutical Crystalline Complex of Methylparaben with Active Pharmaceutical Ingredient (API): Preparation, Structural Characterization, and Solid-State Properties

Abstract In this study, two novel drug–drug (1 : 1) crystalline complexes of methylparaben (MP) with amantadine (AMA) and rotigotine (ROT) were synthesized and systematically investigated. The crystalline complexes were prepared using the slow solvent evaporation technique, using the free-base forms of the APIs prepared from their hydrochloride salts. Formation of the new solid phases was confirmed through comprehensive solid-state characterization using Fourier transform infrared spectroscopy, UV-visible spectroscopy, Differential Scanning Calorimetry, Powder X-ray Diffraction, Single-Crystal X-ray Diffraction, and 1H NMR spectroscopy. Distinct changes in spectral features, diffraction patterns, and thermal behaviour established the successful generation of crystalline complexes different from the parent drug components. The study highlights the effectiveness of drug–drug co-crystallization involving amine-containing CNS drugs as a viable strategy for modulating the solid-state properties of pharmaceutical ingredients.