Molecular modeling and solubility of olopatadine hydrochloride polymorphs

Abstract

Olopatadine hydrochloride is a selective H1 receptor antagonist used in ophthalmic solutions to treat the signs and symptoms of allergic conjunctivitis. This compound presents a phenomenon known as polymorphism, which can cause changes on physicochemical characteristics. Considering the worldwide regulatory requirements for drug registration and the complexity of the pharmacotechnical development of ophthalmic preparations, both supramolecular arrangements (carried out by the Hirshfeld surface) and theoretical calculations (through the quantum theory of atoms in molecules) led to understand the physicochemical properties of polymorphs I and II and possible differences in solubility. The supramolecular arrangement for both polymorphs consists of the chloride anion participating in strong NH ⋯ Cl and OH ⋯ Cl intermolecular interactions as well as two weak CH ⋯ Cl intermolecular interactions, which generate an ionic tetramer. The shape index HS shows the hydrophobic space, which is around the ionic tetramer formed by CH ⋯ π intermolecular interaction for form I as well as π ⋯ π stacking for form II. The supramolecular crystal arrangement provides an essential aspect of its solubility in drug polymorphs.