(178a) The Importance of Using Limiting Flow Rates to Assess the Flowability of Pharmaceuticals, Excipients and Their Mixtures

Reliable flow of pharmaceutical mixtures out of tablet press hoppers is a key to problem-free tablet press operation and consistent tablet properties. Failure to insure reliable flow can result in both considerable manual intervention for the tablet press hopper and poor tablet physical properties such as tablet weight, tablet hardness, etc. Numerous bench top tests are presently used to assess powder flowability such as rotating drums, powder flow out of funnels with variable outlet sizes, etc. In addition, laboratory-scale tablet presses are employed as a small scale model for full-scale operation. However, these tests fail to address the technical complexity, speed, and physics/mechanics of actual full-scale tablet press hopper operation. Many pharmaceutical systems with fine powders (for example, below 100 microns in particle size) exhibit significantly reduced flow rates on account of the two-phase flow which must occur in the conical section of a tablet press hopper. Solids must dilate or reduce in bulk density as they flow in the conical section of a tablet press hopper. If, in the case of fine materials, they are insufficiently permeable to gas flow, then this results in a limiting flow rate of solids. The reduction in flow can be significant and it is not unusual to observe decreases in flow of several orders of magnitude or complete stoppage of flow. This paper will develop the fundamental theory behind limiting flow rates, the key measurements required in order to calculate the limiting flow rate and present several case studies showing the importance of the limiting flow rate approach.