Production Rate Limitations in Pharmaceutical Applications

In the pharmaceutical industry, production rate limitations can develop when tableting/encapsulating fine powders (i.e., below 100 micron in average particle size), such as a direct compression blend or a fine granulation, at high speeds. These feed rate issues are due to the interaction of the material with entrained air. This interaction can result in adverse two-phase (powder:interstitial air) flow effects, such as a feed rate limitations, erratic feed, or flooding from a feed hopper into an encapsulator bowl or a press feed frame. These feed rate problems can result in out-of-specification results for tablet/capsule weight, content uniformity, hardness and dissolution.

We can measure the flow properties of a powder and numerically model its behavior in the feed system to assess if feed rate stability is a concern and, if so, provide corrective actions to provide reliable feed. The corrective actions may include recommended changes to the powder properties and/or feed system equipment.

We commonly measure the following flow properties to assess two-phase flow behavior:

• Particle size distribution by dry laser diffraction;
• Cohesive strength and wall friction;
• Compressibility;
• Permeability (described below).

Permeability is measured as a function of bulk density. In the permeability test set-up (see photo), air is injected at the bottom of the test cell through a permeable membrane. During the test, the flow rate of air is measured at a predetermined pressure drop through a sample of known bulk density. The permeability is then calculated using Darcy's law. A permeability constant is determined from a curve fit of the test results. A lower permeability constant is indicative of a less permeable material.

By inputting the permeability constant along with other material properties into proprietary software, we can model two-phase flow effects and calculate several key parameters throughout the press feed system (see plot below). These calculated outputs are then used to predict if feed rate problems will occur and if modifications to the powder and/or equipment will be successful in achieving target production rates.

It is common that seemingly minor shifts in the powder properties (e.g., "super fines content" in the particle size distribution) or feed system equipment (e.g., a passive vent at a critical point in the feed system) can have a significant effect upon achieving target production rates.

Please contact us if we can be of assistance in assessing the potential for flow problems, including a production rate limitation.