On the possibility of obtaining soft dosage forms based on polyanionic polysaccharides with prolonged yield of drugs

The work is devoted to the creation of liquid and soft gel dosage forms of prolonged action. The main task to be solved in the work was to give certain rheological characteristics (namely, pseudoplastic behaviour and pronounced yield strength) to dosage forms based on solutions of pectin, sodium salt of carboxymethylcellulose and sodium salt of chitosan succinate, namely. The study has found that the effect of prolonging the release of the medicinal substance cefazolin from liquid and soft dosage forms based on polysaccharides is directly related to the rheological characteristics of the system and can manifest itself in two cases. First, it is possible for liquid dosage forms in the area of polymer concentrations in solution lower than the concentration at which the cell of meshes C < C_e is formed. In this case, with an increase in the polymer concentration, there is a decrease in the rate of the drug substance release, due to an increase in the adduct of the polymer-drug reaction Secondly, it is possible for soft gel forms in the region of concentrations greater than the concentration at which the cell of meshes C < C_e is formed, when using additives capable of ionotropic gel formation. Calcium and zinc salts were used as such additives in the work. It is in the case when the modifying additive is capable of forming a “bridging” bond between macromolecules and the gel formation is not accompanied by a decrease in the amount of the complex adduct of the reaction, there is a prolongation effect. If the gel is only formed by increasing the polymer content in the solution without the use of an additive, the compression of macromolecular tangles and the strengthening of intramolecular interaction between the polymer units in a concentrated solution results in a significant decrease in the amount of the polymer-drug reaction adduct and accelerated the drug release from the soft dosage form.

Graphical abstract

Modification of polymer chain