Affiliation:
1. Department of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1 Str., 02-093 Warsaw, Poland
2. Doctoral School, Medical University of Warsaw, Żwirki i Wigury 81 Str., 02-093 Warsaw, Poland
Abstract
Thiamine hydrochloride (THCL), also known as vitamin B1, is an active pharmaceutical ingredient (API), present on the list of essential medicines developed by the WHO, which proves its importance for public health. THCL is highly hygroscopic and can occur in the form of hydrates with varying degrees of hydration, depending on the air humidity. Although experimental characterization of the THCL hydrates has been described in the literature, the questions raised in previously published works suggest that additional research and in-depth analysis of THCL dehydration behavior are still needed. Therefore, the main aim of this study was to characterize, by means of quantum chemical calculations, the behavior of thiamine hydrates and explain the previously obtained results, including changes in the NMR spectra, at the molecular level. To achieve this goal, a series of DFT (CASTEP) and DFTB (DFTB+) calculations under periodic boundary conditions have been performed, including molecular dynamics simulations and GIPAW NMR calculations. The obtained results explain the differences in the relative stability of the studied forms and changes in the spectra observed for the samples of various degrees of hydration. This work highlights the application of periodic DFT calculations in the analysis of various solid forms of APIs.
Funder
Medical University of Warsaw
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science