title: Oscillatory Shear Rheology in Examining the Drug-Polymer Interactions Relevant in Hot Melt Extrusion.
abstract: The flow properties of drug-polymer mixtures have a significant influence on their processability when using techniques such as hot melt extrusion (HME). Suitable extrusion temperature and screw speed to be used in laboratory scale HME were evaluated for mixtures containing 30% of paracetamol (PRC), ibuprofen (IBU), or indomethacin (IND), and 70% of polyethylene oxide, by using small amplitude oscillatory shear rheology. The initial evaluation of the drug:polyethylene oxide solubility was estimated by differential scanning calorimetry of the physical mixtures containing a wide range of weight fractions of the drug substances. Consecutively, the mixtures were extruded, and the maximum plasticizing weight fraction of each drug was determined by means of rheological measurements. IBU was found to have an efficient plasticizing functionality, decreasing the viscosity of the mixtures even above its apparent saturation solubility, whereas IND and PRC initially lowered the viscosity of the mixture slightly but increased it significantly with increasing drug load. The main reason for the enhanced plasticization effect seems to be the lower melting temperature of IBU, which is closer to the used HME temperature, compared to PRC and IND. This study highlights the importance of rheological investigation in understanding the drug-polymer interactions in melt processing.
authors: Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark. Electronic address: johanna.aho@sund.ku.dk.
authors: Johanna
authors: J
authors: Aho
authors: Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark.
authors: Magnus
authors: M
authors: Edinger
authors: Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark.
authors: Johan
authors: J
authors: Botker
authors: Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark. Electronic address: stefania.baldursdottir@sund.ku.dk.
authors: Stefania
authors: S
authors: Baldursdottir
authors: Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark.
authors: Jukka
authors: J
authors: Rantanen
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D006358:Hot Temperature; D007052:Ibuprofen / Q000737:chemistry; D007213:Indomethacin / Q000737:chemistry; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D044367:Phase Transition; D010968:Plasticizers / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012212:Rheology; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D013817:Thermography; D044366:Transition Temperature; D014783:Viscosity
chemical_list: D005079:Excipients; D004364:Pharmaceutical Preparations; D010968:Plasticizers; D000082:Acetaminophen; D011092:Polyethylene Glycols; D007052:Ibuprofen; D007213:Indomethacin
keywords: extrusion; plasticization; polymers; processing; rheology; solubility; viscosity