Direct Measurement of Lateral Molecular Diffusivity on the Surface of Supersaturated Amorphous Solid Dispersions by Atomic Force Microscopy
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Direct Measurement of Lateral Molecular Diffusivity on the Surface of Supersaturated Amorphous Solid Dispersions by Atomic Force Microscopy. / Bannow, Jacob; Karl, Maximilian; Larsen, Peter Emil; Hwu, En Te; Rades, Thomas.
In: Molecular Pharmaceutics, Vol. 17, No. 5, 2020, p. 1715-1722.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Direct Measurement of Lateral Molecular Diffusivity on the Surface of Supersaturated Amorphous Solid Dispersions by Atomic Force Microscopy
AU - Bannow, Jacob
AU - Karl, Maximilian
AU - Larsen, Peter Emil
AU - Hwu, En Te
AU - Rades, Thomas
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - surface mobility
KW - amorphous solid dispersion (ASD)
KW - atomic force microscopy (AFM)
KW - molecular surface diffusivity
KW - indomethacin
KW - soluplus
KW - grating decay
KW - GLASS-TRANSITION TEMPERATURE
KW - PHYSICAL STABILITY
KW - SELF-DIFFUSION
KW - O-TERPHENYL
KW - INDOMETHACIN
KW - CRYSTALLIZATION
KW - SOLUBILITY
KW - BEHAVIOR
KW - STATE
KW - POLY(VINYLPYRROLIDONE)
U2 - 10.1021/acs.molpharmaceut.0c00176
DO - 10.1021/acs.molpharmaceut.0c00176
M3 - Journal article
C2 - 32207959
VL - 17
SP - 1715
EP - 1722
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 5
ER -
ID: 246318464