Effect of hydroxypropyl-beta-cyclodextrin on the solubility of an antibacterial isoxazolyl-naphthoquinone.
The complexation of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4-imine (I) with a highly soluble cyclodextrin, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was studied in aqueous media by solubility methods. I is an antibacterial and trypanocidal agent that is undergoing preclinical testing. Unfortunately, I exhibits low water solubility, and it is therefore difficult to prepare the solutions for biological tests. I inclusion took place with 1:1 stoichiometry. The stability constants of the I complexes calculated from the slope and the intercept of the phase solubility diagrams are larger in the less ionized form, whereas greater overall solubility is obtained in basic media.
Linares
M S
MS
Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Argentina.
de Bertorello
M M
MM
Longhi
M R
MR
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000890:Anti-Infective Agents / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007555:Isoxazoles / Q000737:chemistry*; D009284:Naphthols / Q000737:chemistry*; D012995:Solubility; D014344:Trypanocidal Agents / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins
D000890:Anti-Infective Agents; D003505:Cyclodextrins; D005079:Excipients; D007555:Isoxazoles; D009284:Naphthols; D014344:Trypanocidal Agents; D047392:beta-Cyclodextrins; D014867:Water; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C070800:2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone imine