title: Feasibility of atomic force microscopy for determining crystal growth rates of nifedipine at the surface of amorphous solids with and without polymers.
abstract: Amorphous nifedipine (NFD), which has a smooth surface immediately after preparation, was shown to have structures resembling clusters of curling and branching fibers approximately 1 μm wide by atomic force microscopy (AFM) after storage at 25°C. The size of the cluster-like structures increased with storage over time, implying crystal growth. The average elongation rate of the fibers determined by AFM at ambient room temperature was 1.1 × 10(-9) m/s, and this agreed well with the crystal growth rate of 1.6 × 10(-9) m/s determined by polarized light microscopy. The crystal growth rate of NFD in solid dispersions with 5% polyethylene glycol (PEG) was found to be 5.0 × 10(-8) m/s by AFM. Although this value was approximately the same as that obtained by polarized light microscopy, three-dimensional information obtained by AFM for the crystallization of NFD in a solid dispersion with PEG revealed that the changes in topography were not a consequence of surface crystal growth, but rather attributable to the growth of crystals formed in the amorphous bulk. For solid dispersions with α,β-poly(N-5-hydroxypentyl)-l-aspartamide, acceleration of NFD crystallization by tapping with an AFM probe was observed. The present study has demonstrated the feasibility and application of AFM for interpretation of surface crystallization data.
authors.affiliation: Division of Drugs, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan. miyazaki@nihs.go.jp.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Aso
authors.forename: Toru
authors.initials: T
authors.lastname: Kawanishi
mesh_terms: D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D005079:Excipients / Q000737:chemistry; D005240:Feasibility Studies; D007700:Kinetics; D018625:Microscopy, Atomic Force; D008859:Microscopy, Polarization; D009543:Nifedipine / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D005079:Excipients; D011108:Polymers; D011092:Polyethylene Glycols; D009543:Nifedipine