title: Lonidamine solid dispersions: in vitro and in vivo evaluation.
abstract: Solid dispersions of lonidamine in PEG 4000 and PVP K 29/32 were prepared by the spray-drying method. Then, the binary systems were studied and characterized using differential scanning calorimetry, hot stage microscopy, and x-ray diffractometry. In vitro dissolution studies of the solid dispersed powders were performed to verify if any lonidamine dissolution rate or water solubility improvement occurred. In vivo tests were carried out on the solid dispersions and on the cyclodextrin inclusion complexes to verify if this lonidamine water solubility increase was really able to improve the in vivo drug plasma levels. Drug water solubility was increased by the solid dispersion formation, and the extent of increase depended on the polymer content of the powder. The greater increase of solubility corresponded to the highest content of polymer. Both the solid dispersions and the cyclodextrin complexes were able to improve the in vivo bioavailability of the lonidamine when administered per os. Particularly, the AUC of the drug plasma levels was increased from 1.5 to 1.9-fold depending on the type of carrier.
authors.affiliation: School of Pharmacy, University of Camerino, via S. Agostino no. 1, 62032 Camerino, MC, Italy. gianpalm@camserv.unicam.it
authors.forename: Giovanni Filippo
authors.initials: GF
authors.lastname: Palmieri
authors.forename: Franco
authors.initials: F
authors.lastname: Cantalamessa
authors.forename: Piera
authors.initials: P
authors.lastname: Di Martino
authors.forename: Cinzia
authors.initials: C
authors.lastname: Nasuti
authors.forename: Sante
authors.initials: S
authors.lastname: Martelli
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003505:Cyclodextrins; D007191:Indazoles / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D011092:Polyethylene Glycols; D051381:Rats; D017208:Rats, Wistar; D014961:X-Ray Diffraction
chemical_list: D003505:Cyclodextrins; D007191:Indazoles; D011092:Polyethylene Glycols; C016371:lonidamine