Applying Real Time Release Testing to Powder Processing

How to adapt a real time release approach to powder processing during drug-product manufacturing.
Feb 02, 2011
Volume 35, Issue 2

Real time release testing (RTRT) relies on a thorough knowledge of the materials being processed and the variables within, and influences of, the manufacturing environment. The attributes and quality of the final product depend on both of these contributing factors, and so it is essential that both are well understood.

For example, running a blender at a different speed for two batches of the same formulation has the potential to influence final product attributes, such as dissolution. The powders that go into the blender may be identical, but the fact that one batch has been subjected to more strain than the other means the properties of the output material are likely to be different. For this reason, in this case, it is essential to understand the influence of strain on the properties of the blend.

Equally important are the properties of the materials in the process. If the raw-material properties vary, but the process is fixed (i.e., the same blender speed and time, as noted in the above example) then the output will vary. Recognizing this dependence underpins the essence of quality by design (QbD) and can be conceptualized as: variable input material + fixed process = variable output. What is required is a variable process that is understood well enough to be adjusted to accommodate the unavoidable variability that exists in every batch of raw material.

Herein lies the RTRT challenge. For many years, at least in the powders- processing sector, particle size and distribution has been the primary specification for the physical properties of the materials. However, although size and distribution are important, these are but two of perhaps 20 physical properties that influence bulk material characteristics, which in turn define how the powder behaves during the manufacturing process, as well as the properties of the final product. Additional physical properties might include particle shape, surface area, moisture content, surface texture, and so forth. Each property contributes to the way the powder behaves and the final product attributes.

Understanding the significance of these variables and their contribution is fundamental, however, this relies on the ability to measure the variables and understand their relationship with the process. In addition, RTRT involves finding a way to quantify these important variables during processing. This quanitification must be done within a short timeframe to confirm that the required quality has been achieved and that the intermediate can move on to the next step in the process, or indeed, that the finished product can be released.