A cryospraying process based on expanding dense carbon dioxide as atomizing agent to produce formulated microparticles

Principle

Rapid dense CO₂ expansion:

Induces CO₂ phase transition and density change
Generates temperature gradient
Subtracts heat from surrounding environment
Provides mechanical energy caused by pressure gradient

In direct contact with sprayed product, expanding CO₂ rapidly cools, crystallizes and atomizes the sprayed product to produce solid, fine microparticles.

In this process, active molecules and excipients are melted, dispersed or dissolved in a feeding vessel, under a gaseous CO₂ or other inert gas atmosphere, and subsequently atomized through a nozzle, under controlled pressure and temperature, into a spraying tower.

Here the dense, expanding CO₂ enters in direct contact with the sprayed product, cooling it down to temperatures well below 0ºC, and generating very fine particles. Particles size, surface and bulk properties can be controlled and modified depending on the process conditions and the materials used.

Advantages

Equipment and process capability

The main challenges often faced by novel drug delivery technologies is the cost-effective transition from laboratory bench to larger scales of pilot, clinical and industrial manufacturing.

Too often, promising delivery systems have failed when the transfer from lab bench to an industrially viable process proved not feasible, or too complex and expensive to be profitable.

Cryospraying technology has the advantage to be already established in non-pharmaceutical sectors, where scalability to large volumes and process simplicity are required to guarantee business margins.

Such features represent considerable advantages for pharmaceutical product development.

Lab Scale – Small Pilot Equipment

The equipment is designed with scalability criteria in mind, and with compact dimensions (2.0 x 1.8 x 0.8 m) to fit in a small laboratory space. Lab scale feasibility tests, and small pilot runs (kilo-lab) can be performed. Modular and small scale units can be assembled and operated at clients’ sites.

Pilot Semi-Industrial Equipment

By our collaboration agreement with Messer, scale up tests could be performed using available pilot-scale equipment. Pilot equipment can reach product capacity of 50 to 100 kg/hour, thus making it suitable for small industrial production. (Photo Courtesy of Messer R&D Center).