Novel 1-indanone Thiosemicarbazone Antiviral Candidates: Aqueous Solubilization and Physical Stabilization by Means of Cyclodextrins.
Pharm Res
; 29(3): 739-55, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-21975565
ABSTRACT
PURPOSE:
To investigate cyclodextrin-mediated solubilization and physical stabilization of novel 1-indanone thiosemicarbazone (TSC) candidate drugs that display extremely high self-aggregation and precipitation tendency in water.METHODS:
TSC/CD complexes were produced by co-solvent method, and TSC/CD phase-solubility diagrams were obtained by plotting TSC concentration as a function of increasing CD concentration. Size, size distribution, and zeta-potential of the different TSC/CD complexes and aggregates were fully characterized by dynamic light scattering. The morphology of the structures was visualized by atomic force microscopy.RESULTS:
Results indicated the formation of Type A inclusion complexes; the solubility of different TSCs was enhanced up to 215 times. The study of physical stability revealed that, as opposed to free TSCs that self-aggregate, crystallize, and precipitate in water very rapidly, complexed TSCs remain in solution for at least 1 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 aqueous solubility and physical stability of these new drug candidates and constitute a promising technological approach towards evaluation of their activity against the viruses hepatitis B and C.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article