In situ lipolysis and synchrotron small-angle X-ray scattering for the direct determination of the precipitation and solid-state form of a poorly water-soluble drug during digestion of a lipid-based formulation

Jamal Khan, Adrian Hawley, Thomas Rades, Ben J Boyd

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In situ lipolysis and synchrotron small-angle X-ray scattering (SAXS) were used to directly detect and elucidate the solid-state form of precipitated fenofibrate from the digestion of a model lipid-based formulation (LBF). This method was developed in light of recent findings that indicate variability in solid-state form upon the precipitation of some drugs during the digestion of LBFs, addressing the need to establish a real-time technique that enables solid-state analysis during in vitro digestion. In addition, an ex situ method was also used to analyse the pellet phase formed during an in vitro lipolysis experiment at various time points for the presence of crystalline drug. Fenofibrate was shown to precipitate in its thermodynamically stable crystalline form upon digestion of the medium-chain LBF, and an increase in scattering intensity over time corresponded well to an increase in concentration of precipitated fenofibrate quantified from the pellet phase using high-performance liquid chromatography. Crossed polarised light microscopy served as a secondary technique confirming the crystallinity of the precipitated fenofibrate. Future application of in situ lipolysis and SAXS may focus on drugs, and experimental conditions, which are anticipated to produce altered solid-state forms upon the precipitation of drug (i.e., polymorphs, amorphous forms, and salts).

Original languageEnglish
Pages (from-to)2631-2639
Number of pages9
JournalJournal of Pharmaceutical Sciences
Issue number9
Publication statusPublished - Sept 2016


  • Lipids
  • Poorly water-soluble drugs
  • Precipitation
  • Self-emulsifying
  • Solid state
  • X-ray powder diffraction

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