Kolisnyk T. Development of composition and technology of the tablets with Vaccinium myrtillus leaf extract for diabetes mellitus treatment

The thesis is devoted to the development of composition and technology of the new domestic preparation with Vaccinium myrtillus leaf dry extract «Myrtargin» in the form of prolonged matrix-type tablets for the treatment of type 2 diabetes mellitus (T2DM) and metabolic syndrome with persistent insulin resistance. Based on the available in scientific literature pharmacokinetic and pharmacodynamic properties of biologically active substances (BAS) of bilberry leaf extract “Myrtargin”, the dosage form – prolonged matrix-type tablets – was selected. The wet granulation was substantiated as a method for obtaining matrix-type tablets. The selection of the ratio of release modifiers was accomplished by constructing an artificial neural network using a set of experimental data on the release of extract BAS from model tablets. The in vitro release profile for the tablets with the selected ratios of prolonging agents has been experimentally investigated. By the method of the design of experiment, the optimal parameters for the manufacture of the tablets through wet granulation, such as type of binder agent in the granulating liquid, residual moisture content of tableting mass and the fractional composition of the granulate were substantiated. The rational industrial technology and the methods for quality control of the tablets under the conventional name «Myrtargin retard» were proposed. The methods for the assessment of the risks associated with excipients has been developed and applied for the excipients of «Myrtargin retard» tablets. The compatibility of the extract «Myrtargin» with selected excipients was investigated by the method of thermogravimetric analysis and IR spectroscopy. Pharmacological evaluation of the «Myrtargin retard» tablets as an antidiabetic agent in comparison with active pharmaceutical ingredient (API) and the hypoglycemic drug of synthetic origin – voglibose tablets – revealed that the developed tablets are more effective than API and practically do not inferior to the reference drug.