Formulation and process strategies to minimize coat damage for compaction of coated pellets in a rotary tablet press: A mechanistic view

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• 作者：Min Xu ; Paul Wan Sia Heng ; Celine Valeria Liew ; ^{phalcv@nus.edu.sg" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Coated pellets ; Ethylcellulose coat ; Rotary tableting ; Dwell time ; Compaction pressure ; Pellet volume fraction
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：29 February 2016
• 年：2016
• 卷：499
• 期：1-2
• 页码：29-37
• 全文大小：1387 K

文摘

Compaction of multiple-unit pellet system (MUPS) tablets has been extensively studied in the past few decades but with marginal success. This study aims to investigate the formulation and process strategies for minimizing pellet coat damage caused by compaction and elucidate the mechanism of damage sustained during the preparation of MUPS tablets in a rotary tablet press. Blends containing ethylcellulose-coated pellets and cushioning agent (spray dried aggregates of micronized lactose and mannitol), were compacted into MUPS tablets in a rotary tablet press. The effects of compaction pressure and dwell time on the physicomechanical properties of resultant MUPS tablets and extent of pellet coat damage were systematically examined. The coated pellets from various locations at the axial and radial peripheral surfaces and core of the MUPS tablets were excavated and assessed for their coat damage individually. Interestingly, for a MUPS tablet formulation which consolidates by plastic deformation, the tablet mechanical strength could be enhanced without exacerbating pellet coat damage by extending the dwell time in the compaction cycle during rotary tableting. However, the increase in compaction pressure led to faster drug release rate. The location of the coated pellets in the MUPS tablet also contributed to the extent of their coat damage, possibly due to uneven force distribution within the compact. To ensure viability of pellet coat integrity, the formation of a continuous percolating network of cushioning agent is critical and the applied compaction pressure should be less than the pellet crushing strength.