(68g) Limiting Flow Rate Analysis of Direct Compression Grade Hypromellose and Its Relationship to Powder Flowability
AIChE Annual Meeting
Monday, November 17, 2008 - 2:40pm to 3:00pm
Direct compression (DC) is a tableting process in which a dry blend of ingredients is placed into a tablet hopper and compressed into tablets. Direct compression requires that the powder blend have high flowability. One issue with CR grade hypromellose is poor flowability and its tendency to arch in hoppers. A new grade of hypromellose with a larger mean particle size and improved flow has been developed for direct compression controlled-release applications. This is not the result of decreased particle cohesion (as measured by ring shear tests), but rather improved permeability of the material. This work introduces the concept of limiting flow rates and its importance as a key measure of flowability for fine materials. Limiting flow rate analysis was performed for both grades of hypromellose. Limiting flow rates are caused by the inability of the flowing solid to dilate in the conical section of the hopper as a result of low gas permeability of the bulk solid. The three key measurements used to determine the limiting flow rate are cohesive strength, permeability and compressibility. Cohesive strength is measured in a Schulze RST01.pc shear tester. Compressibility measures the bulk density as a function of load, while permeability measures the air permeation characteristics under similar loads. These data are then used in a program which solves a series of differential equations to determine the limiting flow rate. This paper will examine in detail the key relationships between the permeability, bulk density and the powder flow and how interstitial gas pressure in the conical region of the hopper plays a key role in determining the flow rate of DC mixtures.
As an example, a tablet hopper of specified size with a 6 inch diameter outlet that manufactures 500 mg tablets at a rate of 10,000 tablets per minute requires a flow rate of 660 lbs/hr of material out of the hopper. The limiting flow rate for the DC hypromellose was calculated to be 2400 lbs/hr for a 6 inch diameter outlet, while the flow rate for the CR grade hypromellose was calculated to be 100 lb/hr. The influence of low permeability will be shown to be dramatic with decreases in flow rates being several orders of magnitude, compared to the unimpeded flow rates of coarser materials. For the new DC hypromellose, the improvement in flow is approximately 25 times better than the conventional CR grade hypromellose.