Molecular properties relevant to bioavailability of tioconazole and its derivatives.

The molecular properties of the active substance have an impact on their pharmacokinetics and bioavailability (1). To simplify proof of bioequivalence of generics with reference to medicinal products various exemption procedures and rules were implemented. One of them is substitution of in vivo bioequivalence study by in vitro dissolution similarity determination. This makes a base for so called Biopharmaceutical Classification System (BCS) (2-4). The main two properties are considered: solubility and permeability. Experimental determination of these parameters is cumbersome and frequently impossible. Therefore, in our laboratory we suggested use of theoretically derived determinants as a tool for fast chemical substance classification within BCS (5, 6) and it appeared that they are promising tool for fast chemical substance classification within BCS. The water solubility determination can be efficiently made based on free enthalpy of solvation (∆G), while permeability can be described by the hydrophobic properties in the first approximation. The hydrophobic properties can be established based on solvation energy in solvents with different polarity. In this study we focused on the important from therapeutic view-point antimycotic medicinal products containing the imidazole ring, i.e. for azole antifungal agents, the largest class of synthetic antimycotics. They are frequently used both systemically and topically in the treatment of systemic Candida infections and mycosis (7, 8) and this use is dependent on the properties of particular agent.