Az egyensúlyi oldhatóságot befolyásoló tényezők vizsgálata a helyes meghatározási gyakorlat fejlesztése érdekében
Csicsák Dóra
Pharmaceutical Sciences
Dr. Zelkó Romána
Semmelweis Egyetem, Egyetemi Gyógyszertár Gyógyszerügyi Szervezési Intézet, Zalai terem
2023-07-06 11:00:00
Modern Trends in Pharmaceutical Scientific Research
Dr. Antal István
Dr. Völgyi Gergely
Dr. Jójártné Dr. Laczkovich Orsolya
Dr. Alberti-Dér Ágnes
Dr. Klebovich Imre
Dr. Dunkel Petra
Dr. Szabó Edina
In my PhD work I wanted to provide an overview about the factors affecting the equilibrium solubility by reviewing the traditional SSF method and by incorporating other methods into the measurement protocols, which help to obtain more accurate and reproducible results in the presence of certain factors.
During the revision of the traditional SSF method, the effect of filtration as a phase separation technique on equilibrium solubility was examined. We concluded that the choice of the filter can be critical in terms of the exact concentration determination, and we proposed the selection of the appropriate filter for molecules in different ionization states. The study of the time needed to reach equilibrium was also related to the SSF method. We found in accordance with the previous studies, that 24 hours is most often enough to reach the equilibrium, however, BCS II. classified drugs with poor solubility can be exceptions, so in their case it is recommended to follow the solubility in real time with in situ UV probes, in order to determine the exact equilibrium solubility.
During the examination of the equilibrium solubility of polymorphic forms, we drew attention to the importance of solid-phase analysis, because as a result of the transformations, it helps to determine the identity of the exact compound which is present in solution at the end of the solubility measurement. Raman spectroscopy, XRPD measurements and IR spectroscopy can be suitable for this purpose.
The investigation of the equilibrium solubility of micronized and nanonized active pharmaceutical ingredients in biorelevant and biomimetic media resulted in a complex study about the effect of the particle size reduction, pH, solubilizing agents and polymer excipients on solubility. We have made a recommendation for when it is worth using a biomimetic medium as a solvent for solubility measurements to get the closest result to the solubility of the compound in the gastrointestinal system. We drew attention to the importance of choosing the right excipient for the production of nanonized samples by examining two types of polymer excipients, which are often used in pharmaceutical technology. In addition, we can state that when applying particle size reduction, the solubility measurements must be complemented with solid phase and particle size analysis before and after the measurement, in order to be able to accurately follow the changes that take place during the solubility measurement.
