title: Preparation of two-drug composite microparticles to improve the dissolution of insoluble drug in water for use with a 4-fluid nozzle spray drier.
abstract: In this study, we used a novel 4-fluid nozzle spray drier to prepare composite microparticles of a water-insoluble drug, flurbiprofen (FP), and a water-soluble drug, sodium salicylate (SS), for the purpose of improving the water solubility of FP. An ethanol solution of FP and an aqueous SS solution were simultaneously introduced through different liquid passages in the 4-fluid nozzle spray drier and then spray-dried. Quantitative elemental analysis suggested that the FP/SS ratio in each composite microparticle was nearly the same as the formulation ratio. We also found that SS and FP exist in a low crystallinity state in the composite particles. Release of FP from dissolved composite microparticles was markedly improved because of an increase in the effective surface area following rapid dissolution of SS. This study shows that it is possible to prepare FP-SS composite microparticles using a 4-fluid nozzle spray drier in single process and that this can improve the ability of FP to dissolve in water.
authors.affiliation: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan. ozekit@ps.toyaku.ac.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ozeki
authors.forename: Shuji
authors.initials: S
authors.lastname: Beppu
authors.forename: Takuto
authors.initials: T
authors.lastname: Mizoe
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Takashima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yuasa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okada
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003890:Desiccation; D000431:Ethanol; D005480:Flurbiprofen / Q000008:administration & dosage / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D049329:Nanostructures; D010316:Particle Size; D012980:Sodium Salicylate / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014867:Water; D000431:Ethanol; D005480:Flurbiprofen; D012980:Sodium Salicylate