title: Improved intestinal absorption of a poorly water-soluble oral drug using mannitol microparticles containing a nanosolid drug dispersion.
abstract: A nozzle for a spray dryer that can prepare microparticles of water-soluble carriers containing various nanoparticles in a single step was previously developed in our laboratory. To enhance the solubility and intestinal absorption of poorly water-soluble drugs, we used probucol (PBL) as a poorly water-soluble drug, mannitol (MAN) as a water-soluble carrier for the microparticles, and EUDRAGIT (EUD) as a polymer vehicle for the solid dispersion. PBL-EUD-acetone-methanol and aqueous MAN solutions were simultaneously supplied through different liquid passages of the spray nozzle and dried together. PBL-EUD solid dispersion was nanoprecipitated in the MAN solution using an antisolvent mechanism and rapidly dried by surrounding it with MAN. PBL in the dispersion vehicle was amorphous and had higher physical stability according to powder X-ray diffraction and differential scanning calorimetry analysis. The bioavailability of PBL in PBL-EUD S-100-MAN microparticles after oral administration in rats was markedly higher (14- and 6.2-fold, respectively) than that of the original PBL powder and PBL-MAN microparticles. These results demonstrate that the composite microparticles containing a nanosized solid dispersion of a poorly water-soluble drug prepared using the spray nozzle developed by us should be useful to increase the solubility and bioavailability of drugs after oral administration.
authors.affiliation: Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nishino
authors.forename: Aya
authors.initials: A
authors.lastname: Kubota
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanazawa
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Takashima
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ozeki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okada
mesh_terms: D000284:Administration, Oral; D000818:Animals; D007408:Intestinal Absorption; D008297:Male; D008353:Mannitol / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D049329:Nanostructures; D010599:Pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014867:Water / Q000737:chemistry*
chemical_list: D014867:Water; D008353:Mannitol