Main problems:
Modern medicine involves the use of a wide range of drugs, which must have a specific set of properties necessary to reach the biological receptors. The main problem arising is the extremely low solubility of biologically active substances in physiological media. It is well known that bioavailability is one of the most important pharmacokinetic characteristics of a drug and is determined by the amount of active pharmaceutical ingredient (API) that has reached the systemic circulation. This value, in turn, directly depends on the kinetic and thermodynamic parameters of dissolution. No less important characteristic determining the bioavailability of a drug compound is permeability through the biological barriers (membranes of the intestinal epithelium, blood-brain barrier, etc.). In turn, lipophilicity, the measure of which is the distribution coefficient in the 1-octanol/water model system, makes it possible to estimate the permeability of a substance in a first approximation. Information on the solubility and permeability of candidate substances at the early stages of development is no less relevant than the affinity for the biological receptors. This is due, first of all, to the fact that solving the problem of low solubility at the final stages requires additional research and innovative technologies which makes the process of drug marketing very expensive. A number of approaches aimed at the solubility increasing have been created by now. First of all, this is a directed synthesis of leader compounds based on the search for correlations between the solubility and the crystal lattice structure of the substances in the groups of structural analogs. Secondly, it is the design of multicomponent crystals, the presence of additional components in the composition of which allows improving the properties of the main active pharmaceutical ingredient (API). A huge number of dosage forms are widely known, such as tablets, capsules, injections, suppositories, patches, ointments, etc. Besides the API, they contain various excipients, including those that increase solubility by enhancing the interaction with the solvent - the so-called solubilizers. Biopolymers and cyclodextrins containing the specific fragments exhibiting an affinity for poorly soluble substances and, as a consequence, promoting an increase in the API solubility, have found wide application as solubilizers. However, numerous studies have shown a decrease in the permeability of the biologically active compound in the presence of solubilizing agents. In such a situation, the problem of creating a bioavailable pharmaceutical product is solved by estimating the optimal (in terms of solubility and permeability) concentrations of a solubilizer.
Main directions of research:
- Design and studying the properties of solid dispersions based on active pharmaceutical ingredients (API) and various solubilizing agents;
- Development and studying the properties of supramolecular inclusion complexes in solids and solutions;
- Investigation of API sublimation processes and determination of the thermodynamic characteristics;
- Investigation of the dissolution, solvation, complexation and solubilization processes for API in the presence of solubilizing agents;
- In vitro study of membrane permeability of individual compounds through various types of artificial and synthetic membranes:
- porous phospholipid membrane based on egg lecithin (PVPA);
- membrane based on soy phosphatidylcholine (PermeapadTM);
- membranes based on regenerated cellulose (MWCO 500, 12000-14000 Da).
- Study of the membrane permeability of APIs from solutions in equilibrium with solid dispersions, supramolecular inclusion complexes, and multicomponent crystals (co-crystals);
- Study of the distribution processes of API and supramolecular complexes in model solvent systems 1-octanol/buffer and n-hexane/buffer;
Assessment of the lipophilicity characteristics of compounds and the search for their relationship with membrane permeability;
- Development of the correlation models connecting the parameters of the dissolution, sublimation, solvation, permeability, distribution processes, and the biological activity - on the one hand, and physicochemical descriptors - on the other hand. Development of cluster models for predicting the pharmaceutical properties of individual compounds and complex systems.
- Examination of the influence of solubilizers (biopolymers, cyclodextrins) on the characteristics of solubility and permeability of multicomponent molecular crystals (co-crystals).
Research objects:
Potential neuroprotective agents:
1. 1,2,4-Thiadiazole derivatives:
2. Derivatives of adamantane and memantine
Sulfonamide derivatives:
Antifungal drugs and new compounds with antifungal activity:
