SELECTION OF FILMPROOFERS IN MICROCAPSULATION OF VINPOCETIN

Introduction. The scientific and practical interest in the problem of microencapsulation remains high, as evidenced by the extensive literature on this subject. The choice of a film former as a carrier of the active substance in microencapsulation is determined by its required release rate of the latter, which depends largely on the physical properties of the latter. Biodegradable polymers, sodium alginate and gelatin, are often used as a coating. The aim of the research is a comparative analysis of the thermodynamic characteristics of the release of vinpocetine from microcapsules containing gelatin, sodium alginate as a shell, into water and ethanol. Materials and methods. For calculating the thermodynamic characteristics of the release of vinpocetine from polymers, the conformation of the “polymer-vinpocetine” system after thermodynamic equilibration by the molecular dynamics method in the Bioevrica program was the initial state. Results and discussion. The release of vinpocetine from sodium alginate to water with pH = 2 is an energetically beneficial process, and is accompanied by an increase in entropy, which indicates a higher thermodynamic probability of the final state (vinpocetine in solution). The release of vinpocetine from gelatin into water at pH = 2 is an energetically favorable process, as well as accompanied by an increase in entropy, which indicates a higher thermodynamic probability of the final state (vinpocetine in solution). The release of vinpocetine from sodium alginate to ethanol is energetically less favorable than its release to water. The release of vinpocetine from gelatin to ethanol is energetically less favorable than its release into water. Conclusion. A comparative analysis of the results of the quantum-chemical calculation of the thermodynamic characteristics of the release of vinpocetine from sodium alginate and gelatin makes it possible to conclude that vinpocetine has more affinity for sodium alginate in various environments. As a consequence, there may be a higher degree of vinpocetine release into a solution of HCl 0.01 M and an ethanol from gelatin compared to sodium alginate

MODELING AND ANALYSIS OF MOLECULAR DYNAMICS OF SILICON-SOLVENT-VINPOCETIN SYSTEMS AND SILICON-SOLVENT-VINPOCETIN DIOXIDE

The process of desorption of vinpocetine on the surface of crystalline silicon and silicon oxide in various media has been studied by molecular dynamics modeling. The desorption of vinpocetine in water has been established both from the surface of silicon and from the surface of silicon oxide. The character of the desorption of vinpocetine from silicon and silicon oxide at pH 6.8 and pH 7 differs insignificantly (within the error of the simulation results). The desorption of vinpocetine in acidic medium (pH 2) from silicon and silicon oxide occurs more efficiently and at a higher rate, compared to pH 6.8 and pH 7

DEVELOPMENT OF METHODS OF SIMULATION OF THE INTERACTION OF BIOLOGICALLY ACTIVE SUBSTANCES WITH THE ACTIVE CENTER OF ANGIOTENSIN-CONVERTING ENZYME

Nowadays cardiovascular diseases are the main cause of death among the population around the word. The development of new drugs, giving a possibility to normalize blood pressure, is a promising direction in the field of pharmacy and medicine. Now inhibitors of angiotensinconverting enzyme (ACE) are widely adopted for the treatment of hypertension and chronic heart failure. The principle of action of ACE inhibitors is based on blocking the conversion of angiotensin I into angiotensin II, which mediates vasodilation.The aim of the work is a selection of methods of lisinopril interaction with the active center of angiotensin-converting enzyme by molecular dynamics methods.Materials and methods. Lisinopril molecule was used as a ligand; the charges of that ligand were calculated with the density functional theory (DFT) and ub3lyp method with the basis sets 6-31G* and 6-311G**. Simulation of 75 ns of molecular dynamics of lisinopril interaction with the active center of ACE was carried out in the Bioevrica program. As a result of molecular dynamics simulation, the trajectory of the “lisinopril-ACE” system was obtained. After that a comparison of ligand conformations at different points in simulation time with the experimental conformation of the value of standard deviation of coordinates of atoms was made.Results and discussion.The results of simulation have showed that lisinopril with the charges corresponding to basis set 6-311G** behaves consistent with the x-ray data in the active center of the ACE, in contrast to lisinopril with the charges calculated by basis set 6-31G*.Conclusion. The methods of lisinopril interaction modeling with the active center of angiotensin-converting enzyme has been selected. The obtained technique can be used for studying the interaction of substances, similar in structure to lisinopril with the active center of the enzyme (ACE)

WORKING OUT QUALITY STANDARDS OF MODEL COMPOSITION SAMPLES OF GRANULATED DOSAGE FORM WITH GLUTATHIONE RESTORED

Biologically active sulfur-containing compounds (BASC) exhibit pronounced antioxidant properties. Glutathione reduced (GSH) occupies a particular position among these compounds. It represents a key link in the 3 antioxidant systems of the body from the existing four. Based on the foregoing, a GSH-based dosage form with antioxidant properties was proposed. The aim of this study is to work out a model granulated dosage form based on GSH and methods of its analysis by means of pre-column derivatization with ortho-phthalic aldehyde.Materials and methods. GSH and granulated dosage form based on GSH obtained by wet granulation were used as the object of the study. Quantitative evaluation of GSH content in the obtained granules was carried out using pre-column derivatization by the method of reversed-phase high-performance chromatography (RP HPLC). Ortho-phthalic aldehyde was used as a derivatizing agent. A diode-array detector was used to detect the resulting derivative. Ortho-phthalic aldehyde was used as a derivatizing agent. A diode-matrix detector was used to find out the resulting derivative.Results. In the course of the work, a model dosage form was created – granules based on GSH. By reference to the recommendations on the dosage of the drug, the concentration of the active substance was selected. Lactose was chosen as an auxiliary component. Physical and technological characteristics of a model sample of granules with GSH and lactose as a filler were studied. A method of quantitative determination of GSH in granules using pre-column derivatization with ortho-phthalic aldehyde was developed and validated by HPLC. The method of quantitative determination of GSH in granules with the use of pre-column derivatization by ortho-phthalic aldehyde by HPLC was developed and validated.Conclusion. The developed granulated dosage form meets the requirements given in the pharmacopoeial item “Granules” according to the analyzed indicators. Using the validation evaluation it was established, that the developed methods for the quantitative determination of GSH in granules is correct, precise and specific

Morphological, technological and biopharmaceutical studies of alginate-chitosan microcapsules with vinpocetine

The aim of the investigation is to study morphological, technological and biopharmaceutical properties of alginate-chitosan microcapsules with Vinpocetine.Materials and Methods: Alginate-chitosan microcapsules with different concentrations of sodium alginate (0.5%, 1%, 1.5%, 2%, 2.5% and 3%) and a medium viscosity chitosan solution (0.25-0,5%), as well as microcapsules not treated with a solution of chitosan, were obtained. The surface morphology was studied by methods of atomic-powered microscopy with the use of an NT-MDT Corporation probe scanning microscope (model Solver P47 Pro). To study biopharmaceutical properties of the obtained microcapsules, the "Rotating Basket" apparatus was used.Results: It has been found out that the microcapsules not treated with a chitosan solution, have a smooth, transversely striated surface with large heights and deep cavities. With an increase in the concentration of sodium alginate, the surface becomes smoother, the peaks become larger, higher and wider, the cavities get deeper and more sinuous. The microcapsules treated with a chitosan solution, on the contrary, have a rough surface, low heights and shallow cavities, and with an increase in the concentration of sodium alginate, the surface becomes rougher, the heights are evenly distributed along the microcapsule. The spectrophotometry method was used to determine the efficiency of microencapsulation and the release rate of Vinpocetine from the microcapsules per unit time. When the concentration of a sodium alginate solution is 2.5%, the efficiency of microencapsulation is maximum (86.8%). At this concentration, saturation occurs and with its further increase, the efficiency decreases. The maximum release rate of Vinpocetine from microcapsule samples is observed when the concentration of a sodium alginate solution is 1%: it amounts to 41.17%.Conclusion. The amplitude parameters of the microcapsules surface are different at different concentrations. There is a pattern of alternating signs of asymmetry and excess in the samples with chitosan. With a change in the scale of scanning, the surface characteristics of the microcapsules change. The most distinctive details of the structure are visible at the scale of 2 x 2 pm2. At the concentration of sodium alginate of 2.5%, the efficiency of microencapsulation is maximum (86.8%). Studying the effect of the concentration of a sodium alginate solution on the release rate of Vinpocetine from the microcapsule samples has shown that at the concentration of 1%, the release rate is 41.17%, and at the concentration of 2.5% it is 4.5%. These microcapsules can be used in order to produce capsules with modified release