HPAPIs – A Brief Overview
Highly potent active pharmaceutical ingredients (HPAPIs) are used in formulations for high potency drugs, owing to their availability to target precise disease cells. These substances are pharmacologically and biologically active at low doses.
As the popularity of high potency active pharmaceutical ingredients (HPAPIs) rapidly increases in new drug development, manufacturers are increasingly searching for ways to safely and efficiently process HPAPIs.
To protect operators and the environment from exposure to the cytotoxic properties of HPAPIs, manufacturing facilities that may have only previously processed non-potent APIs are now investing in specialised containment solutions.
High Containment Solutions for Milling HPAPIs
Although conical mills typically produce less dust than alternative milling methods, some dust is still generated due to the high energy involved in reducing particle size. This must be handled responsibly so that users and the environment are not exposed to hazardous airborne powders.
A fully contained milling process is required for the purposes of safety and cross contamination avoidance. The Hanningfield Uni-Mill can be designed to be a completely closed system, thus offering a number of ways to overcome the significant challenges of containing dust. These solutions include Container-to-Container Milling, In-Line Vacuum Transfer, and Milling Inside an Isolator.
Container-to-Container Milling
This solution uses the principle of gravity to feed the product through the mill. By placing an IBC above the mill and then another below the mill, the product is released from the upper IBC, milled, and then fed directly into the lower IBC.
Integrating a split butterfly or high containment valve between the inlet and outlet of two process components creates a fully enclosed method of product transfer with virtually no contact with the machine operator or the process environment. These valves provide the most efficient high integrity method of closed transfer of powders.
In-Line Vacuum Transfer
Another approach to achieve a completely closed system is to move the product pneumatically or under vacuum through a mill that uses closed pipework and hoppers to move the material (such as the Hanningfield Uni-Vac).
Closed-loop vacuum transfer not only contains the dust, but also automates the process and minimises waste – helping customers make efficiency savings. In addition, vacuum transfer through a mill lowers the operating temperature inside the milling chamber; another added benefit to improved processing.
This process ensures that from pick-up to discharge, the system is fully enclosed; preventing the escape of dust and subsequently protecting both the operator and the environment.
Isolator Milling
Another excellent solution for high-containment milling is to use the mill inside an isolator / glove box. By creating a safe environment around the milling head, all excess materials remain enclosed within the booth and ensures that the environment and operators are not exposed to any dust particles.
Hanningfield offers a ‘through the wall’ design for the Uni-Mill which enables the milling head to be contained within the glovebox, while the motor and controls are mounted externally. All cleaning operations are undertaken within the isolator by means of gloves or half-suit, reducing any risk of exposure for the operator and avoiding any transport to the cleaning room. The mill head can be removed from the rest of the body for cleaning simply by releasing a Tri-Clover.
Uni-Mill: Safe and Efficient HPAPI Milling
The Hanningfield Uni-Mill is ideal for high containment milling applications, providing a completely safe and effective solution. All mills are compatible with a wide range of screens and impellers, so a variety of final particle sizes and throughputs can be achieved. The Uni-Mill is suitable for both dry and wet milling applications, and can achieve size reduction down to approximately 150 microns (80 mesh).
Consistently achieving a narrow particle size distribution is critical for milling HPAPIs, as particle size is a critical parameter that affects drug properties such as bioavailability, solubility and product stability. With the Uni-Mill, you can precisely control final particle sizes, reducing the number of rejected, off-specification powders and generating efficiency savings.
Operator safety is of upmost importance in all applications. The Uni-Mill enables HPAPIs to be completely contained while limiting the explosion potential and enabling Operator Exposure Limits (OELs) to be controlled within the strict industry standards.
Our high quality conical mills, coupled with our expertise in milling applications, means that we are proficient in supplying high containment solutions to best suit your application. We work with you to understand your process and guide you through the options available to ensure a fully contained milling process.
Get in Touch
If you would like to speak to one of our experts regarding our range of High-Containment Milling Equipment, or you would like a quote for one of our products, send us a message using our Contact Form or call us on +44 (0)1702 549 777.
To keep up-to-date with the latest news from Hanningfield you can follow us on LinkedIn.