Keywords
laser diffraction spectroscopy
deuterium depleted water (ddw)
water clusters
antibacterial
neuroprotective drugs
kinetic isotope effect (KIEs)
Abstract
In the present work, we provide the results of defining by utilizing Laser diffraction spectroscopy, the kinetic isotopic effect of solvent and constant of dissolution rate κ, s-1 of аn active pharmaceutical ingredient (API) in water with a different content of a stable 12H isotope on the basis of the laws of first-order kinetics. This approach is based on the analysis of the light scattering profile that occurs when the particles of the dispersion phase in the aquatic environment are covered with a collimated laser beam. For the first time, the dependence of the rate of dissolution is demonstrated not only on the properties of the pharmaceutical substance itself (water solubility mg/ml, octanol–water partition coefficient log P oct/water, topological polar surface area, Abraham solvation parameters, the lattice type), but also on the properties of the solvent, depending on the content of stable hydrogen isotope. We show that the rate constant of dissolution of a sparingly hydrophobic substance moxifloxacin hydrochloride (MF · HCl) in the Mili-Q water is: k=1.20±0.14∙10-2 s-1 at 293.15 K, while in deuterium depleted water, it is k=4.24±0.4∙10-2 s-1. Consequently, we have established the development of the normal kinetic isotopic effect (kH/kD >1) of the solvent. This effect can be explained both by the positions of the difference in the vibrational energy of zero levels in the initial and transition states, and from the position of water clusters giving volumetric effects of salvation, depending on the ratio D/H. The study of kinetic isotopic effects is a method that gives an indication of the mechanism of reactions and the nature of the transition state. The effect of increasing the dissolution of the API, as a function of the D/H ratio, we have discovered, can be used in the chemical and pharmaceutical industries in the study of API properties and in the drug production through improvement in soluble and pharmacokinetic characteristics.
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