What is mSAS Technology?

The SAS in mSAS stands for Supercritical Anti-Solvent. Essentially this means that a supercritical fluid, typically carbon dioxide due to its low critical point conditions and attractive physical properties, is used to remove solvent rapidly from a drug solution, allowing the drug to precipitate as dry particles. SAS itself has many advantages, particularly in its ability to crystallise drug molecules and remove solvent such that only parts per million can remain in the final product. However conventional SAS approaches have some limitations. Often these processes are unstable, difficult to scale, and nozzles are prone to blockage.

The Crystec team have pioneered the development of mSAS, a modified SAS process. This unique platform focuses on ensuring that the process used to generate crystals and particles is thermodynamically stable and scalable. The Crystec team have created nozzle designs and configurations which are maintained from the first small-scale research experiments through to commercial GMP scale. The nozzle and vessel assembly encourages ordered crystallisation and particle growth and is not prone to blockage. Generally, it is possible to tune the size of particles from 1 to 25 micron, achieving a tight size distribution.

Crystec’s mSAS process also allows for the incorporation of processing agents into the system, which can be used to favourably manipulate nucleation, particle growth, crystallinity and habit. Furthermore, a second drug (or drugs), functional excipients or additives are able to be introduced into the precipitation chamber, allowing for the production of composite particles of excellent content uniformity. This effectively enables ‘formulating in the particle’ as a single step operation to produce products designed for features such as controlled release, taste masking, combination therapy as well as enhanced bioavailability. Once optimised, the mSAS process typically achieves yields in excess of 95%.

Crystec’s mSAS process is proprietary and is generally licensed for use on a specific product basis.

How does mSAS compare?


As with micronisation (milling) mSAS allows the tuning of mean particle size. However, mSAS particles typically have a much tighter size distribution than equivalent particles manufactured using micronisation. As our mSAS process involves a ‘bottom-up’ precipitation approach, rather than a ‘top down’ size reduction approach, our particles are not mechanically damaged. In addition, they typically have much smoother surfaces, without the unstable amorphous content and the high levels of charge generally seen with micronised product. mSAS products are highly crystalline and often more chemically stable by comparison.

Spray drying

Whilst there have been notable advances in spray drying systems in recent years, the intrinsic nature of the spray drying process is such that material generated is frequently amorphous, whereas mSAS material is generally crystalline (unless amorphous material is specifically required). Amorphous material can cause concerns regarding stability and generally involves a more complex regulatory package. Typically spray drying processes are not as effective as the mSAS process at removing solvent requiring longer drying times which can lead to phase separation for multi-component formulations. Spray drying also routinely involves higher drying temperatures which can be damaging to sensitive molecules.


Sono-crystallisation is a multi-step process, converting product from the amorphous to the crystalline state. The process generates intense energy which can be damaging (hotspots, degradation) to sensitive molecules. By contrast mSAS is a single-stage, rapid and more easily controlled process, carried out at moderate temperatures (typically 40-80⁰C) where the default state of material generated is highly crystalline.


The mSAS process is a substantially faster process than lyophilisation, a widely used drying operation for biomolecules. Typically dry mSAS particles are formed in milliseconds or microseconds. Depending on the material used, lyophilisation can take many hours, and often the residual solvent levels remain high. The duration of lyophilisation provides the opportunity for further reaction, contamination or changes in solid state of the material being dried. The resulting material is often agglomerated or as a cake, which can cause problems with reconstitution.

Advantages of mSAS technology

  • • A single step, high yielding (>95%) and highly reproducible process
  • • Manipulation of solid form (crystal/amorphous)
  • • Control of particle size and morphology
  • • Ability to modify surface properties
  • • Potential to process multiple components in a single particle
  • • Product quality - purity, stability, size distribution
  • • Applicable to small and large molecules
  • • Regulatory approved
Image of mSAS supercritical fluid SCF vessel and process