Natural Therapeutics Crystallization - CRY

Crystallization of natural therapeutics for improved purity and polymorphism


Crystallization is an important step in the purification of organic materials, in particular, therapeutic materials. Improved crystallization processes can provide routes to higher-purity final products. High quality, pure crystals are of great value for a variety of industrial and research applications. For example, a frequent problem in pharmaceutical research is the difficulty of obtaining large single crystals for X-ray structural analyses to determine molecular conformations.

Crystallization is also frequently used as a method of purification in the biotechnology and pharmaceutical industries. More highly ordered crystals will typically result in a more highly purified product. Larger crystals can also impart advantages in packaging and handling operations, and possibly in the manufacture of controlled release materials.

In Aphios' SuperFluids™ crystallization (CRY) process, a supercritical or near-critical fluid is slowly added to a conventional organic liquid solvent containing the solute to be crystallized. Crystallization is caused primarily by the polarity change of the mixture [US Patent].

Examples of CRY Crystals

CRY Paclitaxel-Crystals sm

The anticancer drug paclitaxel (molecular weight 854), active pharmaceutical ingredient of the potent anticancer drug Taxol®, can be crystallized in considerably larger size, improved morphology, higher purity and improved yields (up to 96%) through the use of supercritical and near-critical carbon dioxide with small molar quantities of an acetone co-solvent (SuperFluids™).

We have also demonstrated that the purity of paclitaxel can be increased by as much as 3.5% in a single pass with reduction in levels of certain impurities by as much as 75%.

The SuperFluids™ CRY process has also been successfully utilized to crystallize Bryostatin 1, a marine natural product that has efficacy against cancer and Alzheimer's Disease.

CRY was used to crystallize lipase enzymes which were partially dissolved or suspended in micellar form in acetone.

The SuperFluids™ CRY process appears to be ideally suited for the crystallization of intermediate polarity compounds.

Advantages and Benefits of CRY Crystals

A number of benefits will derive from success in this work at the research scale:

  • A supply of high quality crystals for conformational analyses will add measurably to our understanding of receptor/acceptor interactions.
  • Crystals can be obtained that are larger, more uniform and have fewer inclusions, making X-ray and neutron crystallographic studies easier and less time-consuming.
  • Certain materials that are difficult or have never been crystallized may yield to this new technique.

CRY Applications

Utilizing CRY, we will collaborate with strategic corporate partners to establish crystallization processes of natural products for improved purity and polymorphism.

Contracting/Partnering Opportunity/Technology Transfer

We will contract/partner with biotechnology and pharmaceutical companies to incorporate CRY into your manufacturing process.

We will also provide research-scale units to biotechnology and pharmaceutical companies, universities and research institutions to complement and improve your product and process development activities.


To learn more about the SuperFluids Crystallization Process, click here.