title: Preparation and characterization of fast dissolving pullulan films containing BCS class II drug nanoparticles for bioavailability enhancement.
abstract: The aim of this study is to assess pullulan as a novel steric stabilizer during the wet-stirred media milling (WSMM) of griseofulvin, a model poorly water-soluble drug, and as a film-former in the preparation of strip films via casting-drying the wet-milled drug suspensions for dissolution and bioavailability enhancement. To this end, pullulan films, with xanthan gum (XG) as thickening agent and glycerin as plasticizer, were loaded with griseofulvin nanoparticles prepared by WSMM using pullulan in combination with sodium dodecyl sulfate (SDS) as an ionic stabilizer. The effects of drug loading and milling time on the particle size and suspension stability were investigated, as well as XG concentration and casting thickness on film properties and dissolution rate. The nanosuspensions prepared with pullulan-SDS combination were relatively stable over 7 days; hence, this combination was used for the film preparation. All pullulan-based strip films exhibited excellent content uniformity (most <3% RSD) despite containing only 0.3-1.3 mg drug, which was ensured by the use of precursor suspensions with >5000 cP viscosity. USP IV dissolution tests revealed fast/immediate drug release (t80 < 30 min) from films <120 μm thick. Thinner films, films with lower XG loading, or smaller drug particles led to faster drug dissolution, while drug loading had no discernible effect. Overall, these results suggest that pullulan may serve as an acceptable stabilizer for media milling in combination with surfactant as well as a fast-dissolving film former for the fast release of poorly water-soluble drug nanoparticles.
authors.affiliation: a Otto H. York Department of Chemical, Biological, and Pharmaceutical Engineering , New Jersey Institute of Technology , Newark , NJ , USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Krull
authors.affiliation: a Otto H. York Department of Chemical, Biological, and Pharmaceutical Engineering , New Jersey Institute of Technology , Newark , NJ , USA.
authors.forename: Zhelun
authors.initials: Z
authors.lastname: Ma
authors.affiliation: a Otto H. York Department of Chemical, Biological, and Pharmaceutical Engineering , New Jersey Institute of Technology , Newark , NJ , USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: a Otto H. York Department of Chemical, Biological, and Pharmaceutical Engineering , New Jersey Institute of Technology , Newark , NJ , USA.
authors.forename: Rajesh N
authors.initials: RN
authors.lastname: Davé
authors.affiliation: a Otto H. York Department of Chemical, Biological, and Pharmaceutical Engineering , New Jersey Institute of Technology , Newark , NJ , USA.
authors.forename: Ecevit
authors.initials: E
authors.lastname: Bilgili
mesh_terms: D001682:Biological Availability; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D005936:Glucans / Q000737:chemistry*; D006118:Griseofulvin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D013718:Tensile Strength; D014783:Viscosity
chemical_list: D005936:Glucans; D011135:Polysaccharides, Bacterial; D006118:Griseofulvin; C009109:pullulan; C002563:xanthan gum
keywords: BCS class II drugs; bioavailability enhancement; drug nanoparticles; fast dissolving oral strip film; pullulan; wet-stirred media milling