Journal article
Direct Measurement of Lateral Molecular Diffusivity on the Surface of Supersaturated Amorphous Solid Dispersions by Atomic Force Microscopy
University of Copenhagen1
Department of Health Technology, Technical University of Denmark2
Drug Delivery and Sensing, Department of Health Technology, Technical University of Denmark3
Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics, Department of Health Technology, Technical University of Denmark4
Nanoprobes, Drug Delivery and Sensing, Department of Health Technology, Technical University of Denmark5
Quantifying molecular surface diffusivity is of broad interest in many different fields of science and technology. In this study, the method of surface grating decay is utilized to investigate the surface diffusion of practical relevant amorphous solid dispersions of indomethacin and the polymeric excipient Soluplus (a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) at various polymer concentrations (1-20% w/w).
The study confirms that measuring surface diffusivity below the system's glass transition temperature is possible with a simplified atomic force microscopy setup. Results highlight a striking polymer influence on the surface diffusivity of drug molecules at low polymer concentrations and a turnover point to a polymer dominated diffusion at around three percent (w/w) polymer concentration.
The surface diffusion measurements further correlate well with the observed increase in physical stability of the system as measured by X-ray powder diffraction. These findings are of vital interest in both the applied use and fundamental understanding of amorphous solid dispersions.
Language: | English |
---|---|
Publisher: | American Chemical Society |
Year: | 2020 |
Pages: | 1715-1722 |
ISSN: | 15438392 and 15438384 |
Types: | Journal article |
DOI: | 10.1021/acs.molpharmaceut.0c00176 |
ORCIDs: | 0000-0002-3946-0317 , 0000-0002-7521-6020 and Hwu, En Te |
Amorphous solid dispersion (ASD) Atomic force microscopy (AFM); Grating decay Indomethacin Molecular surface diffusivity Soluplus Surface mobility
BEHAVIOR CRYSTALLIZATION Diffusion Drug Stability GLASS-TRANSITION TEMPERATURE INDOMETHACIN Microscopy, Atomic Force O-TERPHENYL PHYSICAL STABILITY POLY(VINYLPYRROLIDONE) Polyethylene Glycols Polyvinyls SELF-DIFFUSION SOLUBILITY STATE X-Ray Diffraction amorphous solid dispersion (ASD) amorphous solid dispersion(ASD) atomic force microscopy (AFM) grating decay indomethacin molecular surface diffusivity molecularsurface diffusivity polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer soluplus surface mobility