Amorphous water-soluble derivatives of cyclodextrins: nontoxic dissolution enhancing excipients.
Dissolution properties of drugs may be improved by their conversion to an amorphous state or by complexation with cyclodextrins. The present report describes the preparation of cyclodextrin derivatives which are intrinsically amorphous, and water-soluble, and their use as complexation agents. Such derivatives were prepared by condensation of alpha-, beta-, or gamma-cyclodextrins with epoxides (propylene oxide, isobutylene oxide, epichlorohydrin, 1,4-butanediol diglycidyl ether). The condensation products effectively solubilized estradiol, progesterone, or testosterone in water; these solutions, upon freeze-drying, yielded solids which could be directly compressed to tablets which dissolve completely within minutes. Condensation products of cyclodextrins did not have any untoward or toxic effects when administered chronically to mice per os for a 16-week period.
D000818:Animals; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000032:analysis*; D003912:Dextrins / Q000032:analysis*; D004958:Estradiol / Q000032:analysis; D005079:Excipients; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D011374:Progesterone / Q000032:analysis; D012995:Solubility; D013213:Starch / Q000032:analysis*; D013607:Tablets; D013739:Testosterone / Q000032:analysis; D013997:Time Factors
D003505:Cyclodextrins; D003912:Dextrins; D005079:Excipients; D013607:Tablets; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D013213:Starch