Phase Appropriate Crystallization Process Development

Our dedicated group of crystallization experts has a legacy of success in particle engineering and technology transfer. Experienced scientists and engineers offer a fit-for-purpose approach to crystallization processes adapted for each stage of pharmaceutical development. A Quality by Design approach to crystallization process development is used, aiming at the consistent preparation of batches with the desired purity, crystal form and particle properties. This results in reproducible and streamlined downstream processes, including filtration, drying, transfer and storage of the bulk drug substance; and critical performance attributes for drug product formulation and manufacturing.

Design of Crystallization Process

Solid form understanding and preliminary solubility data must be gathered to identify possible crystallization techniques and solvent systems for the design of a scalable process.   Standard solution crystallization techniques include cooling, antisolvent addition, pH swing, reaction, evaporation, and combination of these techniques. Metastable zone width information is collected in systems of interest, to determine suitable seeding conditions and control strategy. On and off-line monitoring during the course of the crystallization may also provide a valuable insight into nucleation and growth of the crystals as well as the polymorphic form. SSCI scientists have access to specialized equipment for crystallization process development, including controlled laboratory reactors from 50 mL to 2L, equipment for solubility and metastable zone width determination, and in situ or at line monitoring of crystal form, supersaturation, nucleation, as well as particle size and morphology.

Process Analytical Technology and Quality by Design

SSCI scientists have access to Process Analytical Technology (PAT) equipment to allow development and optimization of crystallization using a Quality by Design approach:

  • Solubility determination capability
    • Crystal16™
    • solvent addition
    • gravimetric
    • equilibrium solubility with analysis of supernatant by UV-vis, HPLC, or UPLC
  • Controlled laboratory reactors from 50 mL to 2L scale
    • Mettler Toledo EasyMax™ controlled lab reactors (50-100 mL)
    • Radleys Lara™ (100, 250, 500 mL, 1L and 2L)
  • In-situ and off-line monitoring
    • pH
    • Mettler Toledo Turbidity Trb 8300
    • Kaiser Raman RXN3
    • image analysis
  • Filtration
    • vacuum filtration
    • agitated filter drier (up to 2L scale)
    • centrifuge

Crystallization Optimization – What we offer

SSCI can design, optimize or troubleshoot your crystallization process for product purity, recovery or solids separation and isolation. We can provide you with knowledge and understanding of your process to give rise to fewer operation problems by means of:

  • Polymorph Investigations
  • Control & Measurement of Impurities
  • Kinetics of Nucleation & Growth
  • Crystal Size Distribution Measurement & Modification
  • Habit Modification
  • Filtration Studies
  • Drying Investigations