title: Characterization of crystalline drug nanoparticles using atomic force microscopy and complementary techniques.
abstract: OBJECTIVE
  The purpose of this work was to image crystalline drug nanoparticles from a liquid dispersion and in a solid dosage form for the determination of size, shape, and distribution.
  
  
  METHODS
  Crystalline drug nanoparticles were adsorbed from a colloidal dispersion on glass for atomic force microscopy (AFM) imaging. Nanoparticles that were spray coated onto a host bead were exposed by ultramicrotomy for scanning electron microscopy and AFM examination.
  
  
  RESULTS
  The adsorbed drug nanoparticles were measured by AFM to have a mean diameter of 95 nm and an average aspect ratio of 1.3. Nanoparticles observed in the solid dosage form had a size and shape similar to drug nanoparticles in the dispersion. Particle size distribution from AFM measurement agreed well with data from field emission scanning electron microscopy, static light scattering, and X-ray powder diffraction.
  
  
  CONCLUSIONS
  AFM is demonstrated to be a valuable tool in visualization and quantification of drug nanoparticle crystals in formulations. In addition to accurate size measurement, AFM readily provides shape and structural information of nanoparticles, which cannot be obtained by light scattering. Ultramicrotomy is a good sample preparation method to expose the interior of solid dosage forms with minimal structural alteration for microscopic examination.
authors.affiliation: Pharmaceutical R&D, MRL. Merck & Co., Inc., West Point, Pennsylvania 19486, USA. galen_shi@merck.com
authors.forename: Huaiqiu Galen
authors.initials: HG
authors.lastname: Shi
authors.forename: Leon
authors.initials: L
authors.lastname: Farber
authors.forename: James N
authors.initials: JN
authors.lastname: Michaels
authors.forename: Allison
authors.initials: A
authors.lastname: Dickey
authors.forename: Karen C
authors.initials: KC
authors.lastname: Thompson
authors.forename: Suhas D
authors.initials: SD
authors.lastname: Shelukar
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Hurter
authors.forename: Scott D
authors.initials: SD
authors.lastname: Reynolds
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kaufman
mesh_terms: D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004339:Drug Compounding; D008027:Light; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012542:Scattering, Radiation; D014961:X-Ray Diffraction
chemical_list: D004364:Pharmaceutical Preparations; D002482:Cellulose