Lærke Arnfast1, Md Kamruzzaman1, Korbinian Löbmann1, Johanna Aho1, Stefania Baldursdottir1, Thomas Rades1,2, Jukka Rantanen3. 1. Department of Pharmacy, University of Copenhagen, Universitetsparken 2, -2100, Copenhagen, DK, Denmark. 2. Faculty of Science and Engineering, Åbo Akademi University, Tykistökatu 6A, 20521, Turku, Finland. 3. Department of Pharmacy, University of Copenhagen, Universitetsparken 2, -2100, Copenhagen, DK, Denmark. jukka.rantanen@sund.ku.dk.
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.
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.
Entities:
Keywords:
Co-amorphous; HME; Hot melt extrusion; Processability; Rheology
Authors: Michael M Crowley; Feng Zhang; Michael A Repka; Sridhar Thumma; Sampada B Upadhye; Sunil Kumar Battu; James W McGinity; Charles Martin Journal: Drug Dev Ind Pharm Date: 2007-09 Impact factor: 3.225
Authors: Lærke Arnfast; Jeroen van Renterghem; Johanna Aho; Johan Bøtker; Dhara Raijada; Stefania Baldursdóttir; Thomas De Beer; Jukka Rantanen Journal: Pharmaceutics Date: 2020-02-01 Impact factor: 6.321
Authors: Deck Khong Tan; Daniel A Davis; Dave A Miller; Robert O Williams; Ali Nokhodchi Journal: AAPS PharmSciTech Date: 2020-11-08 Impact factor: 3.246