Structural and Physicochemical Studies of Olopatadine Hydrochloride Conformational Polymorphs

• Published in: Journal of pharmaceutical sciences 2016-08, Vol.105 (8), p.2419-2426
• Main Authors: Łaszcz, Marta, Trzcińska, Kinga, Witkowska, Anna, Ciesielska, Agnieszka, Badowska-Rosłonek, Katarzyna, Kuziak, Krzysztof
• Format: Article
• Language: English
• Subjects: Absorption, Physicochemical; Anti-Allergic Agents - chemistry; calorimetry; Crystallization; crystallography; hygroscopicity; infrared spectroscopy; Models, Chemical; Molecular Structure; Olopatadine Hydrochloride - chemistry; physicochemical; polymorphism; Raman spectroscopy; Solubility; Solvents - chemistry; stability; Water - chemistry; X-ray diffractometry
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2016.05.031

Crystal and molecular structures of 2 conformational polymorphs (forms I and II) of olopatadine hydrochloride, an antiallergic agent, are presented. Both crystal modifications crystallize in the monoclinic crystal system with 1 olopatadine hydrochloride molecule in the Z configuration in the asymmetric unit. Molecules are arranged into the centrosymmetric association through the interactions of the intermolecular strong and weak hydrogen bonds of N-H…Cl, O-H…Cl and C-H…Cl, C-H…O types. Conformational change between polymorphs is proved by calculations of a maximum torsion angle deviation (max[Δθ]) and a root-mean-square deviation between the atomic positions (rmsd[r]). The physicochemical characterization of polymorphs is performed by X-ray powder diffraction, infrared and Raman spectroscopy, differential scanning calorimetry. The comparison of the melting points and heats of fusions shows that the forms are monotropically related.