Characterization of crystalline drug nanoparticles using atomic force microscopy and complementary techniques.
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.
Shi
Huaiqiu Galen
HG
Pharmaceutical R&D, MRL. Merck & Co., Inc., West Point, Pennsylvania 19486, USA. galen_shi@merck.com
Farber
Leon
L
Michaels
James N
JN
Dickey
Allison
A
Thompson
Karen C
KC
Shelukar
Suhas D
SD
Hurter
Patricia N
PN
Reynolds
Scott D
SD
Kaufman
Michael J
MJ
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
D004364:Pharmaceutical Preparations; D002482:Cellulose