Elucidation and visualization of solid-state transformation and mixing in a pharmaceutical mini hot melt extrusion process using in-line Raman spectroscopy

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• 作者：Jeroen Van Renterghem^a ; ^{jeroen.vanrenterghem@ugent.be} ; Ashish Kumar^b ; Chris Vervaet^c ; Jean Paul Remon^c ; Ingmar Nopens^b ; Yvan Vander Heyden^d ; Thomas De Beer^a
• 关键词：Hot-melt extrusion ; Raman spectroscopy ; Solid-state transformation ; Residence time distribution ; Mixing ; Transport ; Recirculation time
• 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：119-127
• 全文大小：1919 K
• 卷排序：517

文摘

Mixing of raw materials (drug + polymer) in the investigated mini pharma melt extruder is achieved by using co-rotating conical twin screws and an internal recirculation channel. In-line Raman spectroscopy was implemented in the barrels, allowing monitoring of the melt during processing. The aim of this study was twofold: to investigate (I) the influence of key process parameters (screw speed – barrel temperature) upon the product solid-state transformation during processing of a sustained release formulation in recirculation mode; (II) the influence of process parameters (screw speed – barrel temperature – recirculation time) upon mixing of a crystalline drug (tracer) in an amorphous polymer carrier by means of residence time distribution (RTD) measurements. The results indicated a faster mixing endpoint with increasing screw speed. Processing a high drug load formulation above the drug melting temperature resulted in the production of amorphous drug whereas processing below the drug melting point produced solid dispersions with partially amorphous/crystalline drug. Furthermore, increasing the screw speed resulted in lower drug crystallinity of the solid dispersion. RTD measurements elucidated the improved mixing capacity when using the recirculation channel. In-line Raman spectroscopy has shown to be an adequate PAT-tool for product solid-state monitoring and elucidation of the mixing behavior during processing in a mini extruder.