Melt Extrusion of High-Dose Co-Amorphous Drug-Drug Combinations
Research output: Contribution to journal › Journal article › Research › peer-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 journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
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