Drug Substance

Crystallization Process

Crystallization Process Development
Crystallization is the critical step in solid form control and often those responsible for the development of a crystallization process are not crystallization specialists.  Typically this task is undertaken by a development chemist whose primary focus and principal skill lies in the area of chemical synthesis rather than product isolation.

At SSCI we have wide-ranging experience in all areas of crystallization.  We can take your compound through the stages of generating the first crystals, polymorph screening, salt or cocrystal form selection and on to the development of a robust crystallization process. We will assist you in developing a process that ensures the solid form you manufacture is the one you require, giving you the bulk properties you need, reducing variability, achieving constancy and control.

Developing a Crystallization Process
Solubility data is gathered to identify potential starting and isolation points based on the possible supersaturation generation routes of:  cooling, evaporation, and reaction. Next a scoping crystallization experiment will be undertaken in which the metastable zone width is determined from the proposed starting point. This scoping experiment provides material that can be characterized both in terms of solid-liquid separation performance and specific properties of the crystalline product. On and off-line monitoring during the course of the crystallization provides a valuable insight into nucleation and growth of the crystals as well as the polymorphic form.

Process Analytical Technology and Quality by Design
Recent initiatives within the Food and Drug Administration (FDA) encourage the pharmaceutical industry to build product quality into manufacturing processes rather than test quality into final products. SSCI/Aptuit welcomes the FDA's Process Analytical Technology (PAT) draft guidance. Science-based decision models and quality by design have always been our preferred approach to process and product development, and we have substantial insight and expertise to offer our clients in many areas of monitoring and control.

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