Effects of hydroxypropyl-beta-cyclodextrin on the chemical stability and the aqueous solubility of thalidomide enantiomers.
The aim of this work was to study the effect of hydroxypropyl-beta-cyclodextrin on the solubility and stability of thalidomide enantiomers in aqueous solutions for clinical oral administration to be used in HIV-infected children. For this reason racemic thalidomide was added to solutions containing different concentrations of hydroxypropyl-beta-cyclodextrin. True complexes were obtained by using hydroxypropyl-beta-cyclodextrin and the solubility of both thalidomide enantiomers was increased directly depending on the amount of hydroxylpropyl-beta-cyclodextrin in the medium although no enantioselective differences were observed at 37 degrees C. The chemical stability of thalidomide enantiomers is clearly improved by hydroxypropyl-beta-cyclodextrin. No enantioselective degradation of thalidomide was observed in sodium chloride solution (0.9%) samples stored at 6 degrees C for nine days when hydroxypropyl-beta-cyclodextrin was employed as excipient. Therefore a thalidomide solution suitable for oral administration can be prepared by adding hydroxypropyl-beta-cyclodextrin at 10% (w/v).
Alvarez
C
C
Dpto. Farmacia y Tecnología Farmaceutica, Facultad de Farmacia, Universidad Complutense de Madrid, Spain. covadongaa@farm.ucm.es
Calero
J
J
Menéndez
J C
JC
Torrado
S
S
Torrado
J J
JJ
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005079:Excipients; D007166:Immunosuppressive Agents / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013792:Thalidomide / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry*
D005079:Excipients; D007166:Immunosuppressive Agents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D013792:Thalidomide