Oral Dispersible Tablets of GK-2 [bis-(N-Monosuccinyl-L-Glutamyl-L-Lysine) Hexamethyleneamide]: Optimization of Pressing Process by Mathematical Modeling Based on the Heckel and Kawakita Equations

• Published in: Pharmaceutical chemistry journal 2022-03, Vol.55 (12), p.1390-1394
• Main Authors: Tishkov, S. V., Blynskaya, E. V., Alekseev, K. V., Bueva, V. V.
• Format: Article
• Language: English
• Subjects: Analysis; Drug Synthesis Methods and Manufacturing Technology; Lysine; Medicine; Organic Chemistry; Pharmacology/Toxicology; Pharmacy; Technology application
• ISSN: 0091-150X; 1573-9031
• DOI: 10.1007/s11094-022-02586-2

Optimization of the tablet pressing process is currently an urgent task in the pharmaceutical industry because this technological stage largely determines the behavior of the finished dosage form in the body, during transportation, and in storage. The present work optimized a selected model composition of oral dispersible tablets of GK-2 [ bis -( N -monosuccinyl- L -glutamyl- L -lysine) hexamethyleneamide] for direct pressing technology using mathematical modeling methods based on the Heckel and Kawakita equations. Processes occurring at different pressing forces were considered. Plastic deformation was shown to be prevalent. The fraction of fragmentation was described. The yield point of the composition was estimated. The Kawakita equation was used to estimate the contribution from redistribution of particles during the initial pressing period at low pressures and to determine the pressure at which the tablet mixture volume decreased by 50%. An analysis of the crushing strengths of the tablets yielded a quadratic regression equation that made it possible to predict the strength of tablets produced at various pressing forces. The most acceptable pressing forces for the studied tablet composition were determined based on the obtained data on the optimum range of pressing pressures and the disintegration values.