Physicochemical characterization and in vivo properties of Zolpidem in solid dispersions with polyethylene glycol 4000 and 6000

Solid dispersions and physical mixtures of Zolpidem in polyethylene glycol 4000 (PEG 4000) and 6000 (PEG 6000) were prepared with the aim to increase its aqueous solubility. These PEG based formulations of the drug were chara cterized in solid state by FT-IR spectroscopy, X-ray powder diffraction, an d differential scanning calorimetry. By these physical determinations no dr ug-polymer interactions were evidenced. Both solubility and dissolution rat e of the drug in these formulations were increased. Each individual dissolu tion profile of PEG based formulation fitted Baker-Lonsdale and first order kinetic models. Finally, significant differences in ataxic induction time were observed between Zolpidem orally administered as suspension of drug al one and as solid dispersion or physical mixture. These formulations, indeed , showed almost two- to three-fold longer ataxic induction times suggesting that, in the presence of PEG, the intestinal membrane permeability is prob ably the rate-limiting factor of the absorption process. (C) 1999 Elsevier Science B.V. All rights reserved.