Probing the amorphous state of pharmaceutical compounds within mesoporous material using pair distribution function analysis

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Abstract

Pharmaceutical compounds with poor solubility are loaded within mesoporous materials to understand the effect of mesoscale confinement on their dissolution behavior. Structural and calorimetric characterization is combined with atomic pair distribution function analysis probing the interactions between the silica surface and the loaded amorphous compound. While different degrees of amorphism are not identifiable from X-ray diffraction data or calorimetric techniques, the atomic pair distribution function analysis can help identify local ordering of the drug molecules. Together with a list of drug descriptors such as crystallization properties, molecular size, and glass transition temperature, the behavior of encapsulated compounds and their release kinetics may be rationalized. Dissolution experiments confirm that different release rates can be achieved with small differences in mesopore design, such as the presence of micropores in Santa Barbara Amorphous-15 and loading amount.
Original languageEnglish
Pages (from-to)2216-2224
Number of pages9
JournalJournal of Pharmaceutical Sciences
Volume107
Issue number8
DOIs
Publication statusPublished - Aug 2018

Keywords

  • mesoporous
  • solid dosage forms
  • pair distribution function
  • drug delivery
  • solubility

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