Stricter Quality Control in Pharma Shifts the Balance From Spiral to Opposed Jet Mills

In the pharmaceutical industry, fine particle size and peculiar physical quality attributes achievement for APIs and excipients are a critical step in drug formulation, impacting both efficacy and quality. Traditionally, spiral jet mills have been the technology of choice for this purpose, prized for their simplicity, ease of cleaning, and lack of moving parts. However, this study reveals a significant limitation of spiral jet mills: their performance is highly sensitive to variations in inlet particle size distribution and synthesis stability. Such variability can lead to deviations in the milling process, often requiring adjustments in feed rate and pressure parameters that are typically fixed in the drug’s master file, thus posing regulatory and practical challenges. This paper introduces the opposed jet mill as an innovative solution to this problem. Unlike spiral jet mills, more than gas pressure an opposed jet mills utilizes and the rotational speed of an internal classifier to control particle size. This unique mechanism allows for consistent milling quality regardless of variations in the input material. To substantiate this claim, the paper presents a comparative study involving the milling of pre-milled and non-pre-milled lactose using an opposed jet mill.

The results demonstrate that the opposed jet mill consistently produces a similar particle size distribution for both types of lactose, despite their different physical properties, without the need for altering pre-validated process parameters. The findings suggest that opposed jet mills offer a more reliable and efficient solution for pharmaceutical companies, contract manufacturing organizations (CMOs), and contract development and manufacturing organizations (CDMOs) dealing with variable synthesis quality or unstable raw materials. The adoption of opposed jet mills could significantly reduce the incidence of manufacturing deviations, enhance process stability, and streamline regulatory compliance, thereby offering a potential paradigm shift in pharmaceutical particle size reduction processes.