Background/Requirement for Milling API Slurries
High shear rotor-stator mixers such as the Quadro Ytron® Z Emulsifier and Quadro® HV (High Velocity) Wet Mills are used extensively in the Food, Personal Care, and Chemical Process industries for high shear processing of emulsions, suspensions, and many semi-solid liquid products.
In the Pharmaceutical industry, the Quadro Ytron® Z Emulsifier and Quadro® HV are also employed as slurry and "wet mills" for particle size reduction of API slurries. API materials typically undergo a size reduction step prior to incorporation into a final pharmaceutical dosage tablet or vaccine. Wet mills are often used for conditioning slurries when the API is highly potent and dry handling is undesirable. They are also used for compounds that are susceptible to degradation (i.e. crystalline materials) during dry milling.
Wet Milling, using a Quadro Ytron® Z Emulsifier and Quadro® HV can also be employed in a pharmaceutical milling suite as a pre-milling device, to reduce process time or the number of passes in a media mill or other high energy operation. The equipment best suited for the application depends on the amount of energy required to mill or emulsify the compound to the target particle/droplet size.
Quadro's Approach for Milling API Slurries
The Quadro Ytron® Z Emulsifier and Quadro® HV-Emulsifier and Wet Mill can be used to wet mill or deagglomerate API slurries (solvent-based or aqueous solutions) to reduce the API particle size to the required size range, or to improve the milling efficiency of downstream milling equipment. For example, particle size ranges from 10 - 20 micron are achievable with the HV due to its higher shear output, as compared to other rotor-stator technologies.
Quadro's Z Emulsifier and HV Mills house 1 - 3 sets of rotor-stator tools. Each rotor-stator tool consists of multiple rows of overlapping, slotted teeth with a very fine shear gap (0.25 - <1mm), operating at high rpm. As an API slurry flows through the tooling, it is rapidly accelerated and broken, tangentially and radially through the tooling, resulting in particle and/or droplet fracturing. The desired particle size range for an API material/slurry is achieved by adjusting the parameters of the rotor and stator slot width, number of shear slots, number of stages, tip speed, flow rate, and back pressure. These parameters dial in the appropriate shear rate, shear frequency, and hold-up time which can then be used for predictable and reliable scale-up, and product consistency from laboratory to full production. For example, droplet size reduction in the submicron range with d50 results in the 200 - 300 nm range, are easily attainable with the HV.
Quadro high shear mixing equipment, from single-stage laboratory to multi-stage production scale, can achieve tip speeds to 70 m/s and can with minimal investment be integrated as part of a pharmaceutical processing suite. Exact savings and improvements to a process can be obtained via free product testing at Quadro’s R&D Test Center or via our Rental Program.
The Quadro Ytron® Z Emulsifier and Quadro® HV can improve particle and droplet size distributions, increase product yield (less degradation for certain APIs) and reduce milling time by reducing the number of passes. The Quadro Ytron® Z Emulsifier and Quadro® HV are scalable and have a variety of tooling available to handle specific requirements for both lab and production scale environments.