title: Evaluation of the hydrophobic drug loading characteristics in nanoprecipitated amphiphilic cyclodextrin nanospheres.
abstract: The aim of this work was to evaluate the loading capacity and the association characteristics of the hydrophobic drug progesterone on amphiphilic cyclodextrin nanospheres prepared by the nanoprecipitation method. The colloidal suspensions were prepared in the presence or absence of two different surfactants, Pluronic F68 and Tween 80. The physicochemical characteristics of the nanospheres were assessed using a nanosizer, zetameter, and transmission electron microscope. The physical state of the drug was verified using differential scanning calorimetry (DSC) and x-ray diffraction (XRD) methods. The in vitro progesterone release was investigated at 37 degrees C after dilution of the suspensions in sink conditions. Nanospheres with a mean diameter from 100 to 300 nm and a low degree of polydispersity were prepared from amphiphilic hexanoyl-gamma-cyclodextrin. The progesterone loading capacity was not affected by the formulation parameters tested. The DSC and XRD studies demonstrated the absence of the crystalline domains of progesterone in loaded nanospheres. The DSC studies also demonstrated the presence of interactions between the drug and carrier. The release of the drug from the carrier was extremely rapid and was governed by a partition phenomenon that depends only on the solubility of the drug in the release medium. From these results, we concluded that with this method, the progesterone is molecularly associated at the surface of the cyclodextrin nanospheres, probably through hydrophobic interactions in specific sites. The release profiles obtained can be of value when an improvement in the bioavailability of the drug is desired.
authors.affiliation: URA 1218, Université Paris Sud, Centre d'Etudes Pharmaceutiques, Chatênay-Malabry, France.
authors.forename: E
authors.initials: E
authors.lastname: Lemos-Senna
authors.forename: D
authors.initials: D
authors.lastname: Wouessidjewe
authors.forename: S
authors.initials: S
authors.lastname: Lesieur
authors.forename: F
authors.initials: F
authors.lastname: Puisieux
authors.forename: G
authors.initials: G
authors.lastname: Couarraze
authors.forename: D
authors.initials: D
authors.lastname: Duchêne
mesh_terms: D002152:Calorimetry, Differential Scanning; D003505:Cyclodextrins / Q000737:chemistry*; D004337:Drug Carriers; D005069:Evaluation Studies as Topic; D008854:Microscopy, Electron; D008863:Microspheres; D010316:Particle Size; D011060:Poloxalene; D011136:Polysorbates; D011374:Progesterone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013501:Surface-Active Agents; D014961:X-Ray Diffraction
chemical_list: D003505:Cyclodextrins; D004337:Drug Carriers; D011136:Polysorbates; D013501:Surface-Active Agents; D011374:Progesterone; D011060:Poloxalene