Density fluctuations in amorphous pharmaceutical solids. Can SAXS help to predict stability?

Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

Abstract

The analytical potential of X-ray small-angle scattering (SAXS) combined with simultaneous wide-angle diffraction (WAXS) has been explored on the example of three active pharmaceutical ingredients, (desvenlofaxine, simvastatin, and sulfamerazine, resp.) with the aim of identifying quantitative parameters obtained from SAXS that allow to describe the nano-structural characteristics of different amorphous forms and to monitor the processes of amorphisation and ageing. Cryo-milling, co-milling with polymer, melting and melt-quenching have been used for amorphisation of initially crystalline powders. In parallel to SAXS, the WAXS patterns have been obtained to fingerprint the crystalline state. The SAXS results demonstrate strong, systematic nanostructure variations in amorphous samples obtained by different milling conditions, or by melt-quenching. It has been found that the mean-square density fluctuation, directly obtained from the SAXS invariant, is a sensitive and robust parameter to characterize the degree of nano-heterogeneity, which is related to entropy and hence thermodynamic stability. The SAXS curves also allow estimates of amorphous domain sizes of different density. The propensity to recrystallize or to remain amorphous, respectively, upon ageing has been found to depend on the existence of domains in the starting amorphous materials.
Originalspracheenglisch
Seiten (von - bis) 76-82
Seitenumfang6
FachzeitschriftColloids and Surfaces / B
Jahrgang168
DOIs
PublikationsstatusVeröffentlicht - 2 Mai 2018

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Sulfamerazine
Small Angle Scattering
Simvastatin
Nanostructures
Dermatoglyphics
Entropy
Thermodynamics
Powders
Drug products
Freezing
Polymers
X-Rays
quenching
Pharmaceutical Preparations
Amorphization
amorphous materials
Quenching
ingredients
Aging of materials
Crystalline materials

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Density fluctuations in amorphous pharmaceutical solids. Can SAXS help to predict stability? / Laggner, Peter; Paudel, Amrit.

in: Colloids and Surfaces / B, Jahrgang 168, 02.05.2018, S. 76-82.

Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

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