Novel 1-indanone Thiosemicarbazone Antiviral Candidates: Aqueous Solubilization and Physical Stabilization by Means of Cyclodextrins

Abstract

Purpose: To investigate the cyclodextrin-mediated solubilization and physical stabilization of novel 1-indanone thiosemicarbazone (TSC) candidate drugs that display extremely high selfaggregation and precipitation tendency in water. Methods: TSC/CD complexes were produced by the co-solvent method and TSC/CD phase-solubility diagrams were obtained by plotting the TSC concentration as a function of the increasing CD concentration. The size, size distribution and zeta-potential of the different TSC/CD complexes and aggregates were fully characterized by means of dynamic light scattering. The morphology of the structures was visualized by different microscopy techniques. Results: Results indicated the formation of Type A inclusion complexes; the solubility of the different TSCs was enhanced up to 215 times. The study of the physical stability revealed that, as opposed to free TSC that self-aggregate, crystallize and precipitate in water very rapidly, complexed TSCs remain in solution for at least one week. On the other hand, a gradual size growth was observed. This phenomenon stemmed from the self-aggregation of the TSC/CD complex. Conclusions: 1-indanone TSC/CD inclusion complexes improved the aqueous solubility and physical stability of these new drug candidates and constitute a promising technological approach towards the evaluation of their activity against the viruses of hepatitis B and C.