Characterization of the 3D nanostructure of amorphous solid dispersions
Typ
Examensarbete för masterexamen
Program
Applied physics (MPAPP), MSc
Publicerad
2020
Författare
Olsson, Martina
Modellbyggare
Tidskriftstitel
ISSN
Volymtitel
Utgivare
Sammanfattning
Dissolution enhancing formulation strategies are getting increasingly important for the
pharmaceutical industry as many new upcoming drugs present a poor water solubility. A low
solubility decreases the bioavailability of the drug and diminish the therapeutic effect. One
method that have shown successful results of achieving increased solubility is the formulation
strategy of amorphous solid dispersions which are compound that consist of an amorphous
drug dispersed in a polymer carrier. Despite successful pharmaceutical compounds being
produced these systems are not fully understood, and their formulation are still largely
empirical. One of the key issues is to understand the morphology of the system and how it
affects the pharmaceutical performance to enable a rational design process.
In this thesis the nanostructure is evaluated for a model system of amorphous solid dispersions
consisting of Felodipine in ethyl cellulose. Samples were prepared through hot melt extrusion
and solvent casting with drug loads between 10-80 wt% to evaluate the effect of processing
method and drug load on the morphology. In addition, a partly crystalline sample of hot melt
extruded 50 wt% Carbamazepine in ethyl cellulose was used as a comparison. Ptychographic
X-ray nanotomography was used as the main method together with scanning calorimetry
(DSC) and X-ray-scattering (SAXS/WAXS). The nanotomography resolved the threedimensional
morphology with a resolution of 100 nm and revealed a phase separation in all
samples that were not detected with DSC and X-ray-scattering in the q-range accessible with a
laboratory SAXS station.
The different preparation methods created different morphologies and showed that the
processing method have an effect on the phase separation mechanism. The solvent casted
sample revealed a morphology from phase separation through nucleation and growth while the
hot melt extruded samples showed a pattern characteristic for spinodal decomposition. The
drug load had a minor effect on the extent of phase separation. A low amount of crystallinity
was found in all Felodipine in ethyl cellulose samples and showed that all samples remained
stable in the amorphous state during storage in ambient temperature and humidity over a time
period of three months. The small fraction of crystallinity that was found were detected in the
drug rich phase, indicating that phase separation is an onset for crystallization.
Beskrivning
Ämne/nyckelord
Amorphous solid dispersions , ptychographic X-ray nanotomography , phase separation , 3D morphology , Felodipine