Early detection of capping risk in pharmaceutical compacts

• Published in: International journal of pharmaceutics Vol. 553; no. 1-2; pp. 338 - 348
• Main Authors: Xu, Xiaochi, Vallabh, Chaitanya Krishna Prasad, Hoag, Stephen W., Dave, Vivek S., Cetinkaya, Cetin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.12.2018
• Subjects: Capping risk; Chemistry, Pharmaceutical - methods; Compaction pressure; Compaction speed; Continuous manufacturing; Drug Compounding - methods; Excipients - chemistry; Mannitol - chemistry; Porosity; Pressure; Real-time compaction monitoring; Solid dosage forms; Tablets; Technology, Pharmaceutical - methods; Tensile Strength; Compaction speed; Real-time compaction monitoring; Compaction pressure; Capping risk; Continuous manufacturing; Porosity; Solid dosage forms
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2018.10.052

[Display omitted] 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 non-destructive 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.