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dc.contributor.advisorSkalko-Basnet, Natasa
dc.contributor.authorEkblad, Nicklas
dc.date.accessioned2019-06-06T07:45:36Z
dc.date.available2019-06-06T07:45:36Z
dc.date.issued2018-05-15
dc.description.abstractSoluplus is a suitable excipient for innovative manufacturing techniques such as hot-melt extrusion (HME). While Soluplus is useful for forming amorphous solid dispersions (ASD’s) during HME, the resulting extrudates are often stiff and brittle. In order to achieve suitable dosage forms, with optimal downstream processability, an efficient screening for suitable formulations is required. Vacuum compression moulding (VCM) is a rapid, cost-efficient sample preparation method for thermoplastic materials that could possibly be used as a reliable screening tool. Solid dispersions with 10%, 30% and 50% w/w drug load of naproxen (NAP) or celecoxib (CCX) in Soluplus were prepared by HME and VCM under controlled conditions (HME: 120°C, 0 and 5 min recirculation, 50RPM, VCM: 120°C, 15 min). Melt processability and the effect of drug load were evaluated using rheology, subjecting the samples to a frequency sweep from 100-0.01 Hz at 120°C within the linear viscoelastic region. The samples were also analysed using differential scanning calorimetry (DSC), polarized light microscopy (PLM) and Raman Spectroscopy. The stability during storage of the solid dispersions prepared using HME was also investigated. The complex viscosity (ƞ*) between the different preparative methods varied considerably especially at the higher drug-loads. The lack of mixing and shear forces in VCM leads to less amorphisation and higher crystal content of drug in the mixture, which increases the melt viscosity. The difference is especially evident at higher drug loads where the mixing is critical for forming an ASD. The results also show that the dissolved NAP can act as a plasticizer lowering the melt viscosity of the API-polymer mixture. VCM should be used with consideration when predicting melt properties of melt extrudates, especially at higher drug loads.en_US
dc.identifier.urihttps://hdl.handle.net/10037/15470
dc.language.isoengen_US
dc.publisherUiT Norges arktiske universiteten_US
dc.publisherUiT The Arctic University of Norwayen_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2018 The Author(s)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/3.0en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)en_US
dc.subject.courseIDFAR-3911
dc.subjectPharmaceutical manufacturingen_US
dc.subjectPharmaceutical engineeringen_US
dc.subjectVDP::Technology: 500::Chemical engineering: 560::Pharmaceutical formulation and technology: 568en_US
dc.subjectVDP::Teknologi: 500::Kjemisk teknologi: 560::Farmasøytisk formulering og teknologi: 568en_US
dc.titleMelt processability of amorphous solid dispersions during hot-melt extrusion. Screening using vacuum compression moulding and evaluation by rheology and solid-state analysisen_US
dc.typeMaster thesisen_US
dc.typeMastergradsoppgaveen_US


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Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)