A new method of lyophilisation or freeze drying that uses a single, sterilisable, closed vessel to deliver lump free, fine powder product has the capability to revolutionise the production of bulk pharmaceutical powders.
With the benefits of improved operator safety, reduced equipment requirements and high quality, contaminant-free end product results, the proven, active freeze drying technology, from Hosokawa Micron is making pharmaceutical manufacturers worldwide reconsider their existing tray-type freeze drying methods.
Hosokawa Micron’s active freeze drying technology incorporates the use of a jacketed and stirred dryer and collection filter (Figure 1). Material is quickly frozen inside the vessel.
Figure 1: Active freeze drying: liquid in, powder out
The energy needed for sublimation is applied through the jacket and distributed efficiently throughout the product by the stirrer, which moves the finished dried material — in the form of a fine loose powder — to the filter.
The system is capable of drying solutions, dispersions, pastes and wet solids with successful applications including antibiotics, active pharmaceutical ingredients (APIs), proteins, collagens and electrolytes.
A contained freeze drying system
Gerard Geurtsen, Senior Application Engineer at Hosokawa Micron, explains why this unique closed lyophilisation process is creating such intense interest from pharmaceutical manufacturers.
“Every production step is completed within a single, sterile, closed chamber. There is no dust to compromise operator safety. Nothing can enter the sealed system to contaminate the product and wet product is transferred from a reactor vessel, so no contamination risks associated with manual handling are introduced, and aseptic operation is enabled.”
“When the vacuum is broken on cycle completion,” he adds, “the finished dry powder is discharged directly into a container that was sterilised before product entered the system. There is no requirement for additional containment equipment to protect operators or product during this pack-off stage.”
Lump-free finished product
Unlike the hard baked/crusty material resulting from tray drying, the final product from the Hosokawa system is loose, free flowing and requires no additional crushing stage.
A classification stage may not be required either as the particle size of the final product is often extremely fine and uniform. The product is often porous and, being highly soluble, facilitates its use in injections, etc.
Without the need to introduce a milling stage, the product remains undamaged. “We achieve ‘drying without harming’ of even the most sensitive, delicately structured products and living organisms,” says Gerard.
The fully contained system allows for aseptic processing. Cleaning of the system is easy and effective. There is no need for operatives in suits to be involved. Spray nozzles in the drying chamber start the cleaning and sterilisation process on batch completion. Sterilise-in-place (SIP) is achieved using pressurised steam or vaporised hydrogen peroxide.
Quick drying times owing to the high rate of heat transfer, simple filling and discharge plus the speed of system cleaning ensure that high volume throughputs are achievable with this “single operator” system.
The active freeze drying process is often faster and always less labour intensive than the traditional tray-based freeze drying process, producing lump-free, free flowing powders in one step (Figure 2).
Figure 2: Freeze dried API: traditional versus the active freeze drying process
Consequently, handling times are shorter and simpler, thereby saving time and money. The system is compact, leaving floor space free for other operations and the benefit of a simplified system means there is less equipment to purchase.
Try before you buy
Hosokawa Micron offers a “try before you buy” opportunity, supported by extensive test and toll processing facilities for initial product tests, product development and customer trials.
Explains Gerard Geurtsen: “Our test centre includes 1, 5, 60 and 800 L units available for customer tests and to demonstrate the system’s scale-up potential. We are pleased to work closely with you to assess the specific benefits of active freeze drying for your products.”