title: Development and Characterization of Amorphous Nanofiber Drug Dispersions Prepared Using Pressurized Gyration.
abstract: Nanofibrous systems are attracting increasing interest as a means of drug delivery, although a significant limitation to this approach has been manufacture on a scale commensurate with dosage form production. However, recent work has suggested that nanofibers may be successfully manufactured on a suitable scale using the novel process of pressurized gyration (PG). In this study, we explore the potential of PG as a novel means of generating amorphous solid dispersions of poorly water-soluble drugs with enhanced dissolution performance. We examine the effect of increasing drug loading on fiber properties including size, surface characteristics, and the physical state of both components. Dispersions of ibuprofen in poly(vinylpyrrolidone) (PVP) were prepared (up to 50% w/w loading) and characterized using a range of imaging, thermal, diffraction, and spectroscopic techniques, while the release profiles were studied using sink and non-sink (pH 1.0) conditions. The drug was found to be dispersed on a molecular basis within the fibers; attenuated total reflection FTIR indicated evidence for a direct interaction between the drug and polymer at lower drug loading by the identification of a strong single band in the carbonyl region and amide region of ibuprofen and PVP respectively. Dissolution studies under sink conditions indicated a substantial increase in release rate, while non-sink studies showed evidence for supersaturation. It is concluded that PG presents a viable method for the production of drug-loaded nanofibers for oral administration with enhanced in vitro dissolution rate enhancement.
authors.affiliation: University College London School of Pharmacy , 29-39 Brunswick Square, London, WC1N 1AX, U.K.
authors.forename: Bahijja Tolulope
authors.initials: BT
authors.lastname: Raimi-Abraham
authors.affiliation: Department of Mechanical Engineering, University College London , Torrington Place, London, WC1E 7JE, U.K.
authors.forename: Suntharavathanan
authors.initials: S
authors.lastname: Mahalingam
authors.affiliation: TA Instruments-A Division of Waters U.K. , 730-740 Centennial Court, Centennial Park, Elstree, Hertfordshire, WD6 3SZ, U.K.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Davies
authors.affiliation: Department of Mechanical Engineering, University College London , Torrington Place, London, WC1E 7JE, U.K.
authors.forename: Mohan
authors.initials: M
authors.lastname: Edirisinghe
authors.affiliation: University College London School of Pharmacy , 29-39 Brunswick Square, London, WC1N 1AX, U.K.
authors.forename: Duncan Q M
authors.initials: DQ
authors.lastname: Craig
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry*; D057139:Nanofibers / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011312:Pressure; D012995:Solubility; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D005079:Excipients; D011108:Polymers; D014867:Water; D007052:Ibuprofen
keywords: PVP; amorphous; ibuprofen; pressurized gyration; solid dispersion; supersaturation