TY - JOUR
T1 - Early detection of capping risk in pharmaceutical compacts
AU - Xu, Xiaochi
AU - Vallabh, Chaitanya Krishna Prasad
AU - Hoag, Stephen W.
AU - Dave, Vivek S.
AU - Cetinkaya, Cetin
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/12/20
Y1 - 2018/12/20
N2 - 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.
AB - 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.
KW - Capping risk
KW - Compaction pressure
KW - Compaction speed
KW - Continuous manufacturing
KW - Porosity
KW - Real-time compaction monitoring
KW - Solid dosage forms
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U2 - 10.1016/j.ijpharm.2018.10.052
DO - 10.1016/j.ijpharm.2018.10.052
M3 - Article
C2 - 30367987
AN - SCOPUS:85055634754
SN - 0378-5173
VL - 553
SP - 338
EP - 348
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -