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601g

Granule Strength Determination and Compactibility of Granules of Varying Density

Kevin Macias and M. Teresa Carvajal. Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907

Purpose: The structural dependence of granule strength on the compaction phase was investigated to establish the validity of controlling granule density during high-shear wet granulation to ensure reproducible compaction properties.

Methods: Wet granulations were performed in a Diosna six-liter high-shear granulator equipped with a bottom driven impeller and side mounted chopper. Granulations consisted of 500 grams of Avicel PH 102 and utilized distilled water as the binder. To vary the density of prepared granules, granulations were carried out with impeller speeds of 175, 250 and 500 RPM at water levels corresponding to 50, 60, 70, 80, 90, 100 L/S%. At the 90 L/S% level, wet massing times were varied corresponding to 0, 500 and 7500 impeller revolutions. The chopper speed remained constant at 1000 RPM for all granulations. After drying the granulations, sieve fractions were prepared in order to minimize the effects of size distribution during further analysis. The envelope density of sieve fractions (16, 20, 30, 40 mesh) was measured using the GeoPyc 1360 (Micromeritics). Granule fractions were compressed in tooling on an MTS Sintech 30D load frame equipped with a 20,000lb load cell. Average compressive granule strength was determined using Kawakita analysis. Tensile strength of the resulting compact was calculated using diametral compression.

Results: Granule strength-density relationships were found to be well modeled using the Ryshkewitch-Duckworth model for all prepared granules. A power law relationship was found between granule strength and compact strength for all prepared granules. Upon truncation of granules which yielded poor compacts, Kendall's model was most applicable to describe the granule strength-density relationship and a narrowly linear relationship existed between granule strength and compact strength.

Conclusions: For the current system, the method of preparation did not influence the strength and compaction dependence on granule density. This illustrates that desired compaction properties can be obtained solely by controlling granule density. This systematic approach to process understanding is necessary to advance the transition from traditional, time-based granulation methods to the ideal platform of ensuring product quality during processing.