Low solubility is one of the most common reasons for interrupting the development of active pharmaceutical ingredients, so it is necessary to determine these properties already in the initial stages. Poor solubility means a poorly absorbed compound, which is reflected in a lower effect of the drug. Along with solubility in the initial stages of development we also determine permeability properties, which determine how well the compound will pass through biological barriers, such as cell membranes. Permeability properties tell us what the path of the active ingredient will be to the site of action and thus help us predict the ADME properties of the compound. For compounds we can determine kinetic or thermodynamic solubility. Kinetic solubility is usually determined in the early stages of active ingredient research and thermodynamic solubility is determined later in the drug development phase. In recent years, a number of methods for determining solubility have been developed, and reference methods include the most diverse implementations of determining equilibrium solubility. Determination of permeability properties can be performed with the high-throughput PAMPA in vitro method, which uses a non-biological membrane and mimics the properties of biological barriers. Model carboxylic acid compounds and structurally different CF3-substituted diols, which represent key fragments of bacterial topoisomerase inhibitors, were synthesized at the Department of Pharmaceutical Chemistry at the Faculty of Pharmacy. In the master's thesis, we determined and evaluated the solubility and permeability of these compounds according to their structural properties, where we used data from the literature. To determine the concentrations, we used the HPLC technique, which, given the number of tested compounds, is powerful enough, but also sensitive and selective enough to quantitatively determine all solubilities and identify potential problems with the stability of the investigated compounds during measurements. The obtained results will serve as an aid in optimizing the solubility and permeability of new inhibitors of DNA gyrase and topoisomerase IV.
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