A new perspective on the mechanical evaluation of granular material

Abstract

The mechanical strength of granules is an important parameter to be determined prior to any further downstream formulation processing. It is important to have a good gauge on the granule integrity to forecast any foreseeable powder issues associated with the material processability such as segregation, content uniformity, and material flow-ability. In this study, a systematic methodology has been developed to quantify the integrity of these granules subjected to a low frequency acoustic field to arrive at the Granule Integrity (GI) index. This methodology has been compared to existing well-established bulk characterization techniques reported in the literature such as Heckel analysis, Kawakita analysis, and Young's modulus for four different processed samples. Heckel analysis is more amenable to examine the material deformability while Kawakita analysis is better suited to understand the mechanics of granular material. Individual granule strength measurements to determine Young's modulus often show large variations across the bulk sample. The GI index in conjunction with the Kawakita analysis provides us with more mechanistic insight and understanding into the formation of these granules from a processing perspective. This paper shows the benefits of using the GI index as a practical and direct methodology to characterize the GI of bulk samples in an industrial setting.

Mechanistic Elucidation of Hard Agglomerate Formation from Drying Kinetics in the Integrated Sorption Chamber

“…(TA-8A) travels vertically downward in the compressive mode at a constant speed of 0.01 mm/s until the agglomerate is broken, as evidenced from the abrupt drop in the force profile. Further technical details in the calculation of Young’s modulus, defined as the mechanical strength of the material, have been discussed previously . It should be noted that prior to performing any measurements with the TA TX Plus texture analyzer, a calibration without any sample is performed in order to know the exact position of the ground surface.…”

“…The experimental approach described includes the design of the integrated sorption chamber (ISC), the use of process mass spectrometry (MS) to verify the pattern of vapor concentration profiles (both with API and without API), and the use of gravimetric drying curves to elucidate drying mechanisms. In addition, the method used to characterize the hard agglomerates is documented …”

“…In addition, the method used to characterize the hard agglomerates is documented. 8 The theoretical approach includes the prediction of the concentration profile of the vapor phase and the diffusion model for the removal of water from a thin layer of hard cake. Since the solvent mixture includes both acetone and water, an analytical solution for batch distillation is used to establish the composition trend in the vapor phase.…”

Novel Co-processing Methodology To Enable Direct Compression of a Poorly Compressible, Highly Water-Soluble Active Pharmaceutical Ingredient for Controlled Release

“…The GIT index was calculated by taking the difference between the weight percentages of particles greater than 300 μm before and after the exposure to high-intensity resonant acoustic energy. A GIT index value of 0 refers to complete integrity of granules (i.e., no attrition or breakage to smaller sizes), values less than 0.3 refer to robust granules, values greater than 0.6 refer to fragile granules, and a value of 1 refers to no granule integrity …”

“…A GIT index value of 0 refers to complete integrity of granules (i.e., no attrition or breakage to smaller sizes), values less than 0.3 refer to robust granules, values greater than 0.6 refer to fragile granules, and a value of 1 refers to no granule integrity. 38 The flow characteristics of the co-processed material were determined using an automated rotary split-level shear tester (iShear; E&G Associates, Franklin, IN) with a preconsolidation stress of 3 kPa. The peak torque required to shear the cell was measured as a function of the applied compressive stress.…”