Particle size reduction strategies to improve drug performance

The desired particle size range is created via particle-to-particle impaction at high velocities. The interest in micronisation grew in the pharmaceutical industry because of its advantages for oral and pulmonary drug delivery. There are numerous benefits associated with using micronisation:

• it’s a high yield process in which very little material is lost and no solvents are required, making it an environmentally friendly technology for the pharmaceutical industry
• as long as all the necessary containment equipment and processes are employed effectively, it is compatible with highly potent and extremely toxic APIs
• processing is fast and efficient and the costs are not prohibitive
• the process is easy to scale-up, and thus appropriate for GLP preformulation development, all the way to cGMP clinical supply formulation development and optimisation to full cGMP commercial-scale production
• from a regulatory point of view, micronisation is a proven, viable process that has been used for decades across a wide range of compounds and products, and is well understood by regulatory agencies.

The ability of micronisation to handle smaller batch sizes — less than 5g — makes it easier to determine the feasibility and benefits of particle size reduction for new chemical entities (NCEs). The initial drug discovery phase for investigational new drugs in screening potential candidates is challenging because of the limited quantities available for analytical and performance testing.

Quite often, a mortar and pestle is used for particle size reduction when screening the benefits of an NCE for in vitro testing, for cell culture studies for in vivo with animal studies. Although a mortar and pestle may be convenient and readily available, the nature of the mechanical process can generate heat, and it cannot achieve the desirable uniform particle size distribution that is possible with air jet milling.