Solubilization and dissolution of tamoxifen-hydroxybutenyl cyclodextrin complexes.
The solubility and dissolution of tamoxifen base and tamoxifen citrate with and without hydroxybutenyl-beta-cyclodextrin (HBenBCD) in aqueous and organic media were examined. The solubility of tamoxifen was greatly enhanced by complexation with HBenBCD; pH of the medium, and choice of buffer significantly impacted the amount of drug that could be solubilized. Different tamoxifen:HBenBCD formulations were prepared, including liquid fill capsule formulations, and their dissolution profiles were obtained. These dissolution studies demonstrated that enhanced solubilization of tamoxifen with HBenBCD was effective across a wide variety of formulation options. By complexation of tamoxifen base with HBenBCD, it was possible to obtain solubility and dissolution profiles for tamoxifen base that were essentially identical to that of tamoxifen citrate.
Buchanan
Charles M
CM
Research Laboratories, Eastman Chemical Company, P.O. Box 1972, Kingsport, Tennessee 37662, USA. buck@eastman.com
Buchanan
Norma L
NL
Edgar
Kevin J
KJ
Lambert
Juanelle L
JL
Posey-Dowty
Jessica D
JD
Ramsey
Michael G
MG
Wempe
Michael F
MF
D002021:Buffers; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry; D012995:Solubility; D013629:Tamoxifen / Q000737:chemistry*
D002021:Buffers; D003505:Cyclodextrins; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen