Application of thermal effusivity as a process analytical technology tool for monitoring and control of the roller compaction process

Abstract

The aim of this study was to examine the relationship between physical characteristics of compacted ribbons and their thermal effusivity in an attempt to evaluate the feasibility of using effusivity for in-process monitoring of roller compaction. In this study, thermal effusivity, solid fraction, tensile strength, and Young's modulus of ribbons of microcrystalline cellulose (MCC), anhydrous lactose, and placebo (PBO) formulations containing various ratios of MCC to anhydrous lactose (75:20, 55:40, 40:55, and 20:75) were determined at various compaction pressures (25-150 bars). The effusivity-square root of solid fraction relationship was linear for MCC and all the PBO formulations but was a second-order polynomial function for lactose. This could be due to the predominant deformation of lactose by brittle fracture, which might have significantly increased the number and size of contact points between particles, causing a change in thermal conductivity along with a density change. The effusivity-tensile strength and effusivity-Young's modulus relationships were best described by logarithmic functions for MCC but were linear for lactose up to a compaction pressure of 65 bars. There were similar relationships for effusivity with tensile strength and Young's modulus for all PBO formulations except PBO IV, which might have been due to the deformation of lactose, the largest component in this formulation. Strong correlations between effusivity and physical properties of ribbons were established. Although these correlations were formulation-dependent, they demonstrate the possibility of using effusivity as a tool in monitoring roller compaction.

To Evaluate the Effect of Solvents and Different Relative Humidity Conditions on Thermal and Rheological Properties of Microcrystalline Cellulose 101 Using METHOCEL™ E15LV as a Binder

“…2) , the steep increase in the effusivity value beginning 50% w/w binder solution (water solvent) granules, suggests over-wetting of the granules. And the slurry formation at 65% w/w binder solution implies that the particles are being completely surrounded by water molecules, as the reading is representative of water (48,49).…”

Rapid evaluation for heterogeneities in monoclonal antibodies by liquid chromatography/mass spectrometry with a column-switching system

“…Process analytical technology (PAT) is defined as "a system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality," and along with risk assessment and real-time release testing, is a crucial tool for implementation of QbD [24,26]. PAT plays an important role in evaluating CQA and critical process parameters that affect CQA in manufacturing process development and in validating the manufacturing process of pharmaceutical products [27][28][29][30]. However, challenges remain in developing PAT for manufacturing processes of biopharmaceutical products because they are large, complex, and heterogeneous molecules.…”

Application of Near-Infrared Spectroscopy in Real-Time Monitoring of Product Attributes of Ribbed Roller Compacted Flakes

“…Maintenance of only constant process variables throughout the entire roller compaction operation does not necessarily guarantee the homogeneous quality flakes. In addition, the possibility of heat generation in the compaction region due to friction between the rolls and compacted powder may cause variations in the properties of the flakes during long compaction runs (9). Therefore, a deeper understanding of the process is required to reliably and consistently maintain the desired quality and product performance across a range of environments as part of a quality-by-design approach (10) and process analytical technology (PAT) initiative (11) for real-time measurements of CQA of raw and in-process materials along with process parameters.…”

“…Several nondestructive monitoring techniques have been reported for monitoring the roller compaction process and they include acoustic relaxation emissions from compacted powder (12)(13)(14), thermal effusivity (9), and near-infrared (NIR) spectroscopy (15)(16)(17). Among these methods, NIR spectroscopy has gained the most interest due to its many advantages.…”