Early detection of capping risk in pharmaceutical compacts

Abstract

Capping is a common mechanical defect in tablet manufacturing, exhibited during or after the compression process. Predicting tablet capping in terms of process variables (e.g. compaction pressure and speed) and formulation properties is essential in pharmaceutical industry. In current work, a nondestructive contact ultrasonic approach for detecting capping risk in the pharmaceutical compacts prepared under various compression forces and speeds is presented. It is shown that the extracted mechanical properties can be used as early indicators for invisible capping (prior to visible damage). Based on the analysis of X-ray cross-section images and a large set of waveform data, it is demonstrated that the mechanical properties and acoustic wave propagation characteristics is significantly modulated by the tablet's internal cracks and capping at higher compaction speeds and pressures. In addition, the experimentally extracted properties were correlated to the directly-measured porosity and tensile strength of compacts of Pearlitol®, Anhydrous Mannitol and LubriTose® Mannitol, produced at two compaction speeds and at three pressure levels. The effect compaction speed and pressure on the porosity and tensile strength of the resulting compacts is quantified, and related to the compact acoustic characteristics and mechanical properties. The detailed experimental approach and reported wave propagation data could find key applications in determining the bounds of manufacturing design spaces in the development phase, predicting capping during (continuous) tablet manufacturing, as well as online monitoring of tablet mechanical integrity and reducing batch-to-batch end-product quality variations. Disciplines Disciplines Pharmacy and Pharmaceutical Sciences Comments Comments

Surface Quality Automatic Inspection for Pharmaceutical Capsules Using Deep Learning

“…In the past, surface defects in pharmaceutical products were mainly identified by manual visual inspection, which was too costly and inefficient in meeting the demands of quality control [17]. Nowadays, automated inspection technology based on visual perception is widely used for quality control tasks in industrial manufacturing [18], commodity packaging [19], and fruit grading [20] by replicating and surpassing the effects of the human eye.…”

Development of a Simple In-Die Method for Determination of Capping Tendency in Rotary Tableting Machines

“…The mechanical properties of the ultrasonic approach can be used to determine the indices of invisible capping. 23) Meynard et al measured the RDP using a compaction simulator. A sudden drop in the die-wall pressure was observed for capped tablets during the decompression stage.…”

Multivariate Data Analysis for Tableting Performance Improvement at Industrial Scale. A Case Study Focused on Understanding and Avoiding the Occurrence of Capping and Lamination

“…If capping or lamination tendency is identified during initial development studies, there is still the option to adjust the formulation in order to mitigate this risk, if there is no other impact on the tablet's critical quality attributes [23]. If this tendency is observed during routine manufacturing in recurring manner, this has to trigger an investigation for potential root causes of changes appeared in the potential influencing factors: raw materials, tooling and processing conditions [29]. There are several mechanisms which can explain the capping or lamination defect and they depend on the elastic recovery rate of the compact during the decompression phase (higher than the inter-particles bonding strength), air entrapment during the compaction phase, formation of shear bands during the decompression phase, volume reduction mechanisms, compression speed, stress and density distribution, internal shear stress caused by die wall pressure and friction [1,[27][28][29].…”

“…If this tendency is observed during routine manufacturing in recurring manner, this has to trigger an investigation for potential root causes of changes appeared in the potential influencing factors: raw materials, tooling and processing conditions [29]. There are several mechanisms which can explain the capping or lamination defect and they depend on the elastic recovery rate of the compact during the decompression phase (higher than the inter-particles bonding strength), air entrapment during the compaction phase, formation of shear bands during the decompression phase, volume reduction mechanisms, compression speed, stress and density distribution, internal shear stress caused by die wall pressure and friction [1,[27][28][29]. Most of the mechanisms listed above are related to the stress applied to the tableting mass and products respond differently to stress application at different rates.…”