Melt Extrusion of High-Dose Co-Amorphous Drug-Drug Combinations

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Melt Extrusion of High-Dose Co-Amorphous Drug-Drug Combinations. / Arnfast, Lærke; Kamruzzaman, Md; Löbmann, Korbinian; Aho, Johanna; Baldursdottir, Stefania; Rades, Thomas; Rantanen, Jukka.

In: Pharmaceutical Research, Vol. 34, No. 12, 12.2017, p. 2689-2697.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Arnfast, L, Kamruzzaman, M, Löbmann, K, Aho, J, Baldursdottir, S, Rades, T & Rantanen, J 2017, 'Melt Extrusion of High-Dose Co-Amorphous Drug-Drug Combinations', Pharmaceutical Research, vol. 34, no. 12, pp. 2689-2697. https://doi.org/10.1007/s11095-017-2254-8

APA

Arnfast, L., Kamruzzaman, M., Löbmann, K., Aho, J., Baldursdottir, S., Rades, T., & Rantanen, J. (2017). Melt Extrusion of High-Dose Co-Amorphous Drug-Drug Combinations. Pharmaceutical Research, 34(12), 2689-2697. https://doi.org/10.1007/s11095-017-2254-8

Vancouver

Arnfast L, Kamruzzaman M, Löbmann K, Aho J, Baldursdottir S, Rades T et al. Melt Extrusion of High-Dose Co-Amorphous Drug-Drug Combinations. Pharmaceutical Research. 2017 Dec;34(12):2689-2697. https://doi.org/10.1007/s11095-017-2254-8

Author

Arnfast, Lærke ; Kamruzzaman, Md ; Löbmann, Korbinian ; Aho, Johanna ; Baldursdottir, Stefania ; Rades, Thomas ; Rantanen, Jukka. / Melt Extrusion of High-Dose Co-Amorphous Drug-Drug Combinations. In: Pharmaceutical Research. 2017 ; Vol. 34, No. 12. pp. 2689-2697.

Bibtex

@article{5c5aa464c06941eea2f5405729f5f695,
title = "Melt Extrusion of High-Dose Co-Amorphous Drug-Drug Combinations",
abstract = "PURPOSE: Many future drug products will be based on innovative manufacturing solutions, which will increase the need for a thorough understanding of the interplay between drug material properties and processability. In this study, hot melt extrusion of a drug-drug mixture with minimal amount of polymeric excipient was investigated.METHODS: Using indomethacin-cimetidine as a model drug-drug system, processability of physical mixtures with and without 5{\%} (w/w) of polyethylene oxide (PEO) were studied using Differential Scanning Calorimetry (DSC) and Small Amplitude Oscillatory Shear (SAOS) rheometry. Extrudates containing a co-amorphous glass solution were produced and the solid-state composition of these was studied with DSC.RESULTS: Rheological analysis indicated that the studied systems display viscosities higher than expected for small molecule melts and addition of PEO decreased the viscosity of the melt. Extrudates of indomethacin-cimetidine alone displayed amorphous-amorphous phase separation after 4 weeks of storage, whereas no phase separation was observed during the 16 week storage of the indomethacin-cimetidine extrudates containing 5{\%} (w/w) PEO.CONCLUSIONS: Melt extrusion of co-amorphous extrudates with low amounts of polymer was found to be a feasible manufacturing technique. Addition of 5{\%} (w/w) polymer reduced melt viscosity and prevented phase separation.",
keywords = "Journal Article",
author = "L{\ae}rke Arnfast and Md Kamruzzaman and Korbinian L{\"o}bmann and Johanna Aho and Stefania Baldursdottir and Thomas Rades and Jukka Rantanen",
year = "2017",
month = "12",
doi = "10.1007/s11095-017-2254-8",
language = "English",
volume = "34",
pages = "2689--2697",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer",
number = "12",

}

RIS

TY - JOUR

T1 - Melt Extrusion of High-Dose Co-Amorphous Drug-Drug Combinations

AU - Arnfast, Lærke

AU - Kamruzzaman, Md

AU - Löbmann, Korbinian

AU - Aho, Johanna

AU - Baldursdottir, Stefania

AU - Rades, Thomas

AU - Rantanen, Jukka

PY - 2017/12

Y1 - 2017/12

N2 - PURPOSE: Many future drug products will be based on innovative manufacturing solutions, which will increase the need for a thorough understanding of the interplay between drug material properties and processability. In this study, hot melt extrusion of a drug-drug mixture with minimal amount of polymeric excipient was investigated.METHODS: Using indomethacin-cimetidine as a model drug-drug system, processability of physical mixtures with and without 5% (w/w) of polyethylene oxide (PEO) were studied using Differential Scanning Calorimetry (DSC) and Small Amplitude Oscillatory Shear (SAOS) rheometry. Extrudates containing a co-amorphous glass solution were produced and the solid-state composition of these was studied with DSC.RESULTS: Rheological analysis indicated that the studied systems display viscosities higher than expected for small molecule melts and addition of PEO decreased the viscosity of the melt. Extrudates of indomethacin-cimetidine alone displayed amorphous-amorphous phase separation after 4 weeks of storage, whereas no phase separation was observed during the 16 week storage of the indomethacin-cimetidine extrudates containing 5% (w/w) PEO.CONCLUSIONS: Melt extrusion of co-amorphous extrudates with low amounts of polymer was found to be a feasible manufacturing technique. Addition of 5% (w/w) polymer reduced melt viscosity and prevented phase separation.

AB - PURPOSE: Many future drug products will be based on innovative manufacturing solutions, which will increase the need for a thorough understanding of the interplay between drug material properties and processability. In this study, hot melt extrusion of a drug-drug mixture with minimal amount of polymeric excipient was investigated.METHODS: Using indomethacin-cimetidine as a model drug-drug system, processability of physical mixtures with and without 5% (w/w) of polyethylene oxide (PEO) were studied using Differential Scanning Calorimetry (DSC) and Small Amplitude Oscillatory Shear (SAOS) rheometry. Extrudates containing a co-amorphous glass solution were produced and the solid-state composition of these was studied with DSC.RESULTS: Rheological analysis indicated that the studied systems display viscosities higher than expected for small molecule melts and addition of PEO decreased the viscosity of the melt. Extrudates of indomethacin-cimetidine alone displayed amorphous-amorphous phase separation after 4 weeks of storage, whereas no phase separation was observed during the 16 week storage of the indomethacin-cimetidine extrudates containing 5% (w/w) PEO.CONCLUSIONS: Melt extrusion of co-amorphous extrudates with low amounts of polymer was found to be a feasible manufacturing technique. Addition of 5% (w/w) polymer reduced melt viscosity and prevented phase separation.

KW - Journal Article

U2 - 10.1007/s11095-017-2254-8

DO - 10.1007/s11095-017-2254-8

M3 - Journal article

C2 - 28929263

VL - 34

SP - 2689

EP - 2697

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 12

ER -

ID: 185403463