Local atomic structure determination of the amorphous verapamil HCl drug

• Published in: Journal of non-crystalline solids 2021-08, Vol.565, p.120856, Article 120856
• Main Authors: Bezzon, Vinícius D.N., Ferreira, Fabio F., de Lima, João C.
• Format: Article
• Language: English
• Subjects: Intramolecular characterization; Pair distribution function analysis; Reverse Monte Carlo method; Verapamil hydrochloride; X-ray powder diffraction
• ISSN: 0022-3093; 1873-4812
• DOI: 10.1016/j.jnoncrysol.2021.120856

•Drug amorphization described by pair distribution function and reverse Monte Carlo.•Amorphous verapamil HCl can be obtained by solvent-evaporation technique.•The effect of aging on amorphous verapamil HCl vary with the amorphization method.•Pair distribution function and reverse Monte Carlo methods used in amorphous drug. We investigate the local atomic structure of verapamil hydrochloride in the amorphous state (a-VRPH) using the pair distribution function (PDF) and Reverse Monte Carlo (RMC) methods. We obtain the a-VRPH sample from its crystalline counterpart (c-VRPH) using the solvent evaporation technique. From the measured X-ray powder diffraction (XRPD) data for a-VRPH and c-VRPH, two total structure factors S(Q) are derived, and Fourier transforming them, two total reduced distribution functions, γ(R), are obtained. We refine the XRPD pattern of c-VRPH using the Rietveld method to confirm the sample's crystal structure is the pure c-VRPH. The partial Sij(Q) factors and PDF functions are simulated based on the VRPH crystal structure found in the Cambridge Structural Database® (CSD). The PDF and RMC analyses allow us to observe some similarities between a-VRPH and c-VRPH at the intramolecular level and the main differences at the intermolecular level induced by the amorphization process.