TY - JOUR

T1 - Near-infrared chemical imaging (NIR-CI) of 3D printed pharmaceuticals

AU - Khorasani, Milad

AU - Edinger, Magnus

AU - Raijada, Dharaben Kaushikkumar

AU - Bøtker, Johan

AU - Aho, Johanna

AU - Rantanen, Jukka

PY - 2016/12/30

Y1 - 2016/12/30

N2 - Hot-melt extrusion and 3D printing are enabling manufacturing approaches for patient-centred medicinal products. Hot-melt extrusion is a flexible and continuously operating technique which is a crucial part of a typical processing cycle of printed medicines. In this work we use hot-melt extrusion for manufacturing of medicinal films containing indomethacin (IND) and polycaprolactone (PCL), extruded strands with nitrofurantoin monohydrate (NFMH) and poly (ethylene oxide) (PEO), and feedstocks for 3D printed dosage forms with nitrofurantoin anhydrate (NFAH), hydroxyapatite (HA) and poly (lactic acid) (PLA). These feedstocks were printed into a prototype solid dosage form using a desktop 3D printer. These model formulations were characterized using near-infrared chemical imaging (NIR-CI) and, more specifically, the image analytical data were analysed using multivariate curve resolution-alternating least squares (MCR-ALS). The MCR-ALS algorithm predicted the spatial distribution of IND and PCL in the films with reasonable accuracy. In the extruded strands both the chemical mapping of the components in the formulation as well as the solid form of the active compound could be visualized. Based on the image information the total nitrofurantoin and PEO contents could be estimated., The dehydration of NFMH to NFAH, a process-induced solid form change, could be visualized as well. It was observed that the level of dehydration increased with increasing processing time (recirculation during the mixing phase of molten PEO and nitrofurantoin). Similar results were achieved in the 3D printed solid dosage forms produced from the extruded feedstocks. The results presented in this work clearly demonstrate that NIR-CI in combination with MCR-ALS can be used for chemical mapping of both active compound and excipients, as well as for visualization of solid form variation in the final product. The suggested NIR-CI approach is a promising process control tool for characterization of innovative patient-centred medicinal products.

AB - Hot-melt extrusion and 3D printing are enabling manufacturing approaches for patient-centred medicinal products. Hot-melt extrusion is a flexible and continuously operating technique which is a crucial part of a typical processing cycle of printed medicines. In this work we use hot-melt extrusion for manufacturing of medicinal films containing indomethacin (IND) and polycaprolactone (PCL), extruded strands with nitrofurantoin monohydrate (NFMH) and poly (ethylene oxide) (PEO), and feedstocks for 3D printed dosage forms with nitrofurantoin anhydrate (NFAH), hydroxyapatite (HA) and poly (lactic acid) (PLA). These feedstocks were printed into a prototype solid dosage form using a desktop 3D printer. These model formulations were characterized using near-infrared chemical imaging (NIR-CI) and, more specifically, the image analytical data were analysed using multivariate curve resolution-alternating least squares (MCR-ALS). The MCR-ALS algorithm predicted the spatial distribution of IND and PCL in the films with reasonable accuracy. In the extruded strands both the chemical mapping of the components in the formulation as well as the solid form of the active compound could be visualized. Based on the image information the total nitrofurantoin and PEO contents could be estimated., The dehydration of NFMH to NFAH, a process-induced solid form change, could be visualized as well. It was observed that the level of dehydration increased with increasing processing time (recirculation during the mixing phase of molten PEO and nitrofurantoin). Similar results were achieved in the 3D printed solid dosage forms produced from the extruded feedstocks. The results presented in this work clearly demonstrate that NIR-CI in combination with MCR-ALS can be used for chemical mapping of both active compound and excipients, as well as for visualization of solid form variation in the final product. The suggested NIR-CI approach is a promising process control tool for characterization of innovative patient-centred medicinal products.

KW - Hot-melt extrusion

KW - Near-infrared chemical imaging

KW - Multivariate data analysis

KW - MCR-ALS

KW - Patient-centered medicinal products

U2 - 10.1016/j.ijpharm.2016.09.075

DO - 10.1016/j.ijpharm.2016.09.075

M3 - Journal article

C2 - 27720877

VL - 515

SP - 324

EP - 330

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1–2

ER -