title: Complexation of zolpidem with 2-hydroxypropyl-beta-, methyl-beta-, and 2-hydroxypropyl-gamma-cyclodextrin: effect on aqueous solubility, dissolution rate, and ataxic activity in rat.
abstract: The effect of some chemically modified cyclodextrins [namely, 2-hydroxypropyl-beta-, methyl-beta-, and 2-hydroxypropyl-gamma-cyclodextrin (HP-beta-CD, Me-beta-CD, and HP-gamma-CD, respectively)] on the aqueous solubility and dissolution rate of the hypnotic agent Zolpidem (ZP) was investigated. Solid complexes were prepared by freeze drying and characterized by infrared spectroscopy, X-ray powder diffraction, and differential scanning calorimetry. The solubility and dissolution rate of the drug were significantly improved by complexation with HP-beta-CD or Me-beta-CD. The structure of the inclusion complex ZP-HP-beta-CD in CH(3)COOD/D(2)O was investigated by (1)H and (13)C NMR spectroscopy, including NOE measurements. These measurements revealing a weak interaction between the tolyl moiety of the guest molecule and the HP-beta-CD cavity. The ataxic activity in rat was also investigated and it was found that ZP-HP-beta-CD and ZP-Me-beta-CD complexes showed almost 2-fold longer ataxic induction times than controls.
authors.affiliation: Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Via Orabona 4, 70125 Bari, Italy. trapani@farmchim.uniba.it
authors.forename: G
authors.initials: G
authors.lastname: Trapani
authors.forename: A
authors.initials: A
authors.lastname: Latrofa
authors.forename: M
authors.initials: M
authors.lastname: Franco
authors.forename: M R
authors.initials: MR
authors.lastname: Pantaleo
authors.forename: E
authors.initials: E
authors.lastname: Sanna
authors.forename: F
authors.initials: F
authors.lastname: Massa
authors.forename: F
authors.initials: F
authors.lastname: Tuveri
authors.forename: G
authors.initials: G
authors.lastname: Liso
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D001259:Ataxia / Q000139:chemically induced; D003505:Cyclodextrins / Q000009:adverse effects / Q000737:chemistry*; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000737:chemistry*; D008297:Male; D011725:Pyridines / Q000009:adverse effects / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D000077334:Zolpidem; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins
chemical_list: D003505:Cyclodextrins; D006993:Hypnotics and Sedatives; D011725:Pyridines; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins; C479659:hydroxypropyl-gamma-cyclodextrin; C108732:methyl-beta-cyclodextrin; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000077334:Zolpidem; C023792:gamma-cyclodextrin