Solid Form Characterization and Pre-formulation studies 

The new solid forms that are found in our screenings are characterized at Enantia in order to identify and select the most suitable form for development.

We also offer full comprehensive characterization that will be required by the regulatory agencies for NDA and ANDA filings (or Marketing Authorisation and Abridged applications in the EU). This is useful, for example, to clearly identify the unit cell of a crystalline solid form, to differentiate if a form is a salt or a cocrystal, and to provide comparative solubilities and stability assessments.

X ray diffractometer used in Enantia’s services for solid form characterization and pre-formulation studies to ensure stability, solubility and regulatory compliance.
Physicochemical characterization and pre-formulation studies of candidates and drug substances performed at Enantia:
  • Crystalline phase identification by X-ray powder diffraction (XRPD)

  • Thermal analysis by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)

  • Hygroscopicity and water activity by dynamic vapor sorption (DVS), TGA and Karl Fischer (KF)

  • Composition and stoichiometry by NMR and Elemental analysis 

  • Relative polymorph stability and identification of the most stable polymorph through slurry competition studies

  • Unequivocal solid form confirmation by single crystal X-ray diffraction (SCXRD), Electron Diffraction (ED), solid state NMR (ssNMR), Fourier Transform Infrared (FTIR) spectroscopy, and Raman spectroscopy. Unit cell and absolute configuration determination.

  • Morphology and Particle characterization by optical microscopy, Scanning Electron Microscope (SEM), Polarized Light Microscopy (PLM) and Particle Size Distribution (PSD) analysis.

  • Stability studies (chemical and crystallographic) in chambers with controlled temperature and relative humidity.

  • Solubility studies at defined media (buffered solutions and biorelevant media like FeSSIF, FaSSIF, FaSSIGF)
    – Thermodynamic and kinetic solubility
    – Dissolution and reprecipitation trends for cocrystals and salts
    – Intrinsic dissolution rate for drug substances (Woods apparatus)
    – Determination of solubility curves and metastable zone width

  • Excipient compatibility