(421h) API Micronization Strategy for De-Risking the Pathway to Commercialization

Fluid energy micronization of Active Pharmaceutical Ingredients (APIs) is a commonly utilized unit operation for enhancing active drug substance exposure related to Oral Solid Dosage (OSD) formulations of crystalline BCS Class II APIs. This exposure enhancement stems from an increase in API drug substance solubility, which results from an overall reduction in primary particle size of the API particles. In the pharmaceutical industry, the most dominant equipment used for this purpose is the jet mill micronizer, where two specific mill designs are directly applicable to these types of API particle size reduction processes. These are the spiral jet mill and the loop type jet mill. This presentation will detail the experience of scaling up the micronization of a specific investigational BCS Class II API that required a unique set of powder property specifications to prevent undesired processing problems during the downstream formulation activities. Due to this requirement for tighter control of the micronized API powder properties, and to de-risk the overall scale up to a commercial micronization process, a deeper understanding of how the selected jet mill design would influence process performance and robustness was required for maximizing the probability of a successful commercialization. In support, milling process equipment details from pilot and commercial scale activities will also be discussed along with associated data from pilot scale process development and commercial technology transfer activities. Finally, a summary of key lessons learned will be listed along with high-level guidance on how to leverage this information during process development to proactively screen for situations where equipment specific attributes related to the type of jet mill can become important towards ensuring a successful scale up of an API micronization process.