In-line monitoring of compaction properties on a rotary tablet press during tablet manufacturing of hot-melt extruded amorphous solid dispersions

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• 作者：W. Grymonpré ; ^a ; G. Verstraete^a ; P.J. Van Bockstal^b ; J. Van Renterghem^b ; P. Rombouts^c ; T. De Beer^b ; J.P. Remon^a ; C. Vervaet^a ; ^{Chris.Vervaet@UGent.be}
• 关键词：Amorphous polymers ; Hot-melt extrusion ; Powder compaction ; In-line monitoring ; Rotary tablet press ; Multivariate data analysis
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：30 January 2017
• 年：2017
• 卷：517
• 期：1-2
• 页码：348-358
• 全文大小：2000 K
• 卷排序：517

文摘

As the number of applications for polymers in pharmaceutical development is increasing, there is need for fundamental understanding on how such compounds behave during tableting. This research is focussed on the tableting behaviour of amorphous polymers, their solid dispersions and the impact of hot-melt extrusion on the compaction properties of these materials. Soluplus, Kollidon VA 64 and Eudragit EPO were selected as amorphous polymers since these are widely studied carriers for solid dispersions, while Celecoxib was chosen as BCS class II model drug. Neat polymers and physical mixtures (up to 35% drug load) were processed by hot-melt extrusion (HME), milled and sieved to obtain powders with comparable particle sizes as the neat polymer. A novel approach was used for in-line analysis of the compaction properties on a rotary tablet press (Modul P, GEA) using complementary sensors and software (CDAAS, GEA). By combining ‘in-die’ and ‘out-of-die’ techniques, it was possible to investigate in a comprehensive way the impact of HME on the tableting behaviour of amorphous polymers and their formulations. The formation of stable glassy solutions altered the formulations towards more fragmentary behaviour under compression which was beneficial for the tabletability. Principal component analysis (PCA) was applied to summarize the behaviour during compaction of the formulations, enabling the selection of Soluplus and Kollidon VA 64 as the most favourable polymers for compaction of glassy solutions.