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Calendering as a direct shaping tool for the continuous production of fixed-dose combination products via co-extrusion |
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| Institution: | 1. Canadian Centre for Agri-food Research in Health and Medicine, St Boniface Hospital Albrechtsen Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada;2. Department of Physiology and Pathophysiology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada;3. Department of Human Nutritional Sciences, Faculty of Human Ecology, University of Manitoba, Winnipeg, Manitoba, Canada;4. Canadian International Grain Institute, Winnipeg, Canada;5. Department of Surgery, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada;1. Department of Chemistry, Graduate School, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, Republic of Korea;2. Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul 130701, Republic of Korea;3. Department of Applied Chemistry and Institute of Natural Sciences, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, Republic of Korea |
| Abstract: | In this study calendering is used as a downstream technique to shape monolithic co-extruded fixed-dose combination products in a continuous way. Co-extrudates with a metoprolol tartrate-loaded sustained-release core and a hydrochlorothiazide-loaded immediate-release coat were produced and immediately shaped into a monolithic drug delivery system via calendering, using chilled rolls with tablet-shaped cavities. In vitro metoprolol tartrate release from the ethylcellulose core of the calendered tablets was prolonged in comparison with the sustained release of a multiparticulate dosage form, prepared manually by cutting co-extrudates into mini-matrices. Analysis of the dosage forms using X-ray micro-computed tomography only detected small differences between the pore structure of the core of the calendered tablet and the mini-matrices. Diffusion path length was shown to be the main mechanism behind the release kinetics. Terahertz pulsed imaging visualized that adhesion between the core and coat of the calendered tablet was not complete and a gradient in coat thickness (varying from 200 to 600 μm) was observed. Modulated differential scanning calorimetry and X-ray diffraction indicated that the solid-state properties of both drugs were not affected by the calendering procedure. |
| Keywords: | Calendering Co-extrusion Continuous production Fixed-dose combination product Sustained release Immediate release HME"} {"#name":"keyword" "$":{"id":"k0040"} "$$":[{"#name":"text" "_":"hot-melt extrusion FDC"} {"#name":"keyword" "$":{"id":"k0050"} "$$":[{"#name":"text" "_":"fixed-dose combination MPT"} {"#name":"keyword" "$":{"id":"k0060"} "$$":[{"#name":"text" "_":"metoprolol tartrate HCT"} {"#name":"keyword" "$":{"id":"k0070"} "$$":[{"#name":"text" "_":"hydrochlorothiazide EC"} {"#name":"keyword" "$":{"id":"k0080"} "$$":[{"#name":"text" "_":"ethylcellulose PEO"} {"#name":"keyword" "$":{"id":"k0090"} "$$":[{"#name":"text" "_":"polyethylene oxide PEG"} {"#name":"keyword" "$":{"id":"k0100"} "$$":[{"#name":"text" "_":"polyethylene glycol MDSC"} {"#name":"keyword" "$":{"id":"k0110"} "$$":[{"#name":"text" "_":"modulated differential scanning calorimetry XRD"} {"#name":"keyword" "$":{"id":"k0120"} "$$":[{"#name":"text" "_":"X-ray diffraction DBS"} {"#name":"keyword" "$":{"id":"k0130"} "$$":[{"#name":"text" "_":"dibutyl sebacate MW"} {"#name":"keyword" "$":{"id":"k0140"} "$$":[{"#name":"text" "_":"molecular weight USP"} {"#name":"keyword" "$":{"id":"k0150"} "$$":[{"#name":"text" "_":"United States Pharmacopeia UV"} {"#name":"keyword" "$":{"id":"k0160"} "$$":[{"#name":"text" "_":"ultraviolet glass transition temperature RCS"} {"#name":"keyword" "$":{"id":"k0180"} "$$":[{"#name":"text" "_":"refrigerated cooling system TPI"} {"#name":"keyword" "$":{"id":"k0190"} "$$":[{"#name":"text" "_":"terahertz pulsed imaging Micro-CT"} {"#name":"keyword" "$":{"id":"k0200"} "$$":[{"#name":"text" "_":"micro-computed tomography BMP"} {"#name":"keyword" "$":{"id":"k0210"} "$$":[{"#name":"text" "_":"bitmap ROI"} {"#name":"keyword" "$":{"id":"k0220"} "$$":[{"#name":"text" "_":"region of interest |
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