title: Fast dissolution of poorly water soluble drugs from fluidized bed coated nanocomposites: Impact of carrier size.
abstract: Formation of core-shell nanocomposites of Fenofibrate and Itraconazole, model poorly water soluble drugs, via fluidized bed (FB) coating of their well-stabilized high drug loaded nanosuspensions is investigated. Specifically, the extent of dissolution enhancement, when fine carrier particles (sub-50μm) as opposed to the traditional large carrier particles (>300μm) are used, is examined. This allows testing the hypothesis that greatly increased carrier surface area and more importantly, thinner shell for finer carriers at the same drug loading can significantly increase the dissolution rate when spray-coated nanosuspensions are well-stabilized. Fine sub-50μm lactose (GranuLac®200) carrier particles were made fluidizable via dry coating with nano-silica, enabling decreased cohesion, fluidization and subsequent nanosuspension coating. For both drugs, 30% drug loaded suspensions were prepared via wet-stirred media milling using hydroxypropyl methyl cellulose and sodium dodecyl sulfate as stabilizers. The stabilizer concentrations were varied to affect the milled particle size and prepare a stable nanosuspension. The suspensions were FB coated onto hydrophilic nano-silica (M-5P) dry coated sub-50μm lactose (GranuLac®200) carrier particles or larger carrier particles of median size >300μm (PrismaLac®40). The resulting finer composite powders (sub-100μm) based on GranuLac®200 were freely flowing, had high bulk density, and had much faster, immediate dissolution of the poorly water-soluble drugs, in particular for Itraconazole. This is attributed to a much higher specific surface area of the carrier and corresponding thinner coating layer for fine carriers as opposed to those for large carrier particles.
authors.affiliation: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Azad
authors.affiliation: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Moreno
authors.affiliation: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors.forename: Ecevit
authors.initials: E
authors.lastname: Bilgili
authors.affiliation: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA. Electronic address: dave@njit.edu.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Davé
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D011345:Fenofibrate / Q000737:chemistry*; D000960:Hypolipidemic Agents / Q000737:chemistry; D065347:Hypromellose Derivatives / Q000737:chemistry; D017964:Itraconazole / Q000737:chemistry*; D007785:Lactose / Q000737:chemistry; D053761:Nanocomposites / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D012822:Silicon Dioxide / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D000960:Hypolipidemic Agents; D017964:Itraconazole; D012967:Sodium Dodecyl Sulfate; D065347:Hypromellose Derivatives; D012822:Silicon Dioxide; D007785:Lactose; D011345:Fenofibrate
keywords: Fast dissolving nanocomposite powders; Fine vs large carrier particles; Fluidized bed coating; Poorly water soluble drug; Thick vs thin polymer coating; Wet-stirred media milling