The improved cargo loading and physical stability of ibuprofen orodispersible film: molecular mechanism of ion-pair complexes on drug-polymer miscibility

Abstract High drug cargo loading in polymer and physical stability was essential for the development of orodispersible film (ODFs) due to the small amount of excipients used in a thin film. The present study aimed to investigate the mechanism of ion-pair strategy in improving drug cargo loading and physical stability of drug in ODFs. The results showed that the ion-pair, especially IBU-ethanolamine, improved the drug solubility in polymer up to 60% (w/w) and physical stability by 30% than the pure IBU film. In addition, drug dissolution rate was increased over two times. The high drug cargo loading, physical stability and drug dissolution rate was derived from the improved the drug-polymer miscibility introduced by the formation of ion-pair complex. Investigations from the standpoint of physicochemical properties, intermolecular interaction and polymer mobility indicated the modulation mechanism of ion-pair complexes in the ODFs at molecular level. The amino group and –OH of counter ion exhibited strong hydrogen bond forming ability, which increased the bilateral interaction with both drug and polymer, delayed the onset temperature of sublimation and decreased the polymer mobility. Therefore, ion-pair technology is a promising strategy for high drug loading ODFs in improving the drug-excipient miscibility and stability.