TY - JOUR

T1 - The flow properties and presence of crystals in drug-polymer mixtures

T2 - Rheological investigation combined with light microscopy

AU - Aho, J

AU - Van Renterghem, J

AU - Arnfast, L

AU - De Beer, T

AU - Rantanen, J

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2017/8/7

Y1 - 2017/8/7

N2 - The presence of solid matter in polymer melts affects the rheological properties of a drug-polymer mixture, and thus the processability of these mixtures in melt-based processes. The particle morphological changes related to dissolution and crystal growth in the mixtures of paracetamol and ibuprofen with polyethylene oxide and methacrylate copolymer (Eudragit(®) E PO) were observed by polarized microscopy simultaneously while measuring their rheological properties within temperature ranges relevant for melt processes, such as hot melt extrusion and fused deposition modeling 3D printing. The dissolution of solid crystalline matter into the molten polymer and its effects on the rheological parameters showed that the plasticization effect of the drug was highly dependent on the temperature range, and at a temperature high enough, plasticization induced by the small-molecule drugs could enhance the flowability even at very high drug loads. Therefore, even supersaturated mixtures can be plasticized efficiently, enabling their melt processing, such as hot melt extrusion or 3D printing. The combination of rheometry and polarized light microscopy proved to be very useful for studying the link between morphological changes in the drug-polymer and the flow behavior of the drug-polymer mixtures at different temperature ranges and deformation modes.

AB - The presence of solid matter in polymer melts affects the rheological properties of a drug-polymer mixture, and thus the processability of these mixtures in melt-based processes. The particle morphological changes related to dissolution and crystal growth in the mixtures of paracetamol and ibuprofen with polyethylene oxide and methacrylate copolymer (Eudragit(®) E PO) were observed by polarized microscopy simultaneously while measuring their rheological properties within temperature ranges relevant for melt processes, such as hot melt extrusion and fused deposition modeling 3D printing. The dissolution of solid crystalline matter into the molten polymer and its effects on the rheological parameters showed that the plasticization effect of the drug was highly dependent on the temperature range, and at a temperature high enough, plasticization induced by the small-molecule drugs could enhance the flowability even at very high drug loads. Therefore, even supersaturated mixtures can be plasticized efficiently, enabling their melt processing, such as hot melt extrusion or 3D printing. The combination of rheometry and polarized light microscopy proved to be very useful for studying the link between morphological changes in the drug-polymer and the flow behavior of the drug-polymer mixtures at different temperature ranges and deformation modes.

KW - Journal Article

U2 - 10.1016/j.ijpharm.2017.06.012

DO - 10.1016/j.ijpharm.2017.06.012

M3 - Journal article

C2 - 28614694

VL - 528

SP - 383

EP - 394

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -