Thesis-2013-Grazier.pdf (13.74 MB)
Characterisation of amorphous pharmaceutical materials
thesis
posted on 2013-08-20, 12:06 authored by Jeffery N. GrazierSmall quantities of amorphous content can have a profound influence on the properties of a material,
however their instability means that quantifying amorphous content over time is important for proving
the stability of a drug. Quantifying amorphous content in α-lactose monohydrate by solid state 13C CP
MAS NMR, has been carried out by use of proton saturation recovery relaxation and differentiating
between spectra by partial least squares (PLS), however these techniques have not proved sensitive on
their own, this work investigates their sensitivity in combination. Crystalline α-lactose monohydrate
and a rapidly quenched melt were combined to create a set of calibration mixes, whose spectra were
recorded using proton saturation recovery relaxations ranging from 2 to 60 seconds. This technique
showed a limit of detection of 0.17% (LOD = intercept + 3xSy/x), with a relaxation delay of 15 s and was
able to recognise amorphous materials generated by spray and freeze drying. The atmospheric effects
on the proton saturation recovery relaxation times of different amorphous lactose preparations were
investigated. This found that an oxygen atmosphere reduced the relaxation times, of amorphous
lactose that was prepared from a rapidly quenched melt. The loss of moisture from spray dried and
freeze dried samples to less than 1% removed the significance of this effect.
Lactose is an important excipient in pharmaceuticals and a key ingredient of confectionary, very little
research has been carried out in to the quantification of the isomers of different preparations of
amorphous lactose. This work quantifies the isomer content by Gas Chromatography with Flame
Ionisation Detection (GC-FID) using a DB-17 15m 0.53mm 1.00 μm column and derivatisation with N-
(trimethylsilyl)imidazole. [Continues.]
Funding
Loughborough University & 3M Pharmaceuticals
History
School
- Science
Department
- Chemistry