Evaluation of Poorly Soluble Drugs' Dissolution Rate by Laser Scattering in Different Water Isotopologues

The most important task in the design of dosage forms is to modify the pharmaceutical substances structure in order to increase solubilization, targeted delivery, controlled rate of drug administration, and its bioavailability. Screening-laboratory (in vitro) or computer (in silico)-as a procedure for selecting a prototype for the design of a drug molecule, involves several years of research and significant costs. Among a large number of solvents and diluents (alcohol, ether, oils, glycerol, Vaseline) used in the pharmaceutical industry for the manufacture of drugs water finds the greatest application. This is because all biological reactions (reactions in living systems) take place in water and distribution of the fluid in the body and the substances found within is critical for the maintenance of intracellular and extracellular functions. Modern studies in the field of the stable isotopic compositions of natural water and its structure and properties make it possible to use isotopic transformations of the water to improve the pharmacokinetic properties of medicinal substances without previous structural modification. It is known that by replacing any of the atoms in the reacting substance molecule with its isotope, it is possible to record changes in the reactivity, which are expressed as a change in the reaction rate constant, i.e., in the manifestation of the kinetic isotope effect (KIE). The article presents the results of studies on the effect of the kinetic isotope effect of a solvent-water-on increasing the solubility and dissolution rate constants of poorly soluble drugs using laser diffraction spectroscopy. The results of the studies can be successfully implemented in pharmaceutical practice to overcome the poor solubility of medicinal substances of classes II and IV, according to the biopharmaceutical classification system (BCS), in water for pharmaceutical purposes by performing its preliminary and safe isotopic modification.