2 research outputs found
Second Harmonic Generation Guided Raman Spectroscopy for Sensitive Detection of Polymorph Transitions
Second harmonic generation
(SHG) was integrated with Raman spectroscopy
for the analysis of pharmaceutical materials. Particulate formulations
of clopidogrel bisulfate were prepared in two crystal forms (Form
I and Form II). Image analysis approaches enable automated identification
of particles by bright field imaging, followed by classification by
SHG. Quantitative SHG microscopy enabled discrimination of crystal
form on a per particle basis with 99.95% confidence in a total measurement
time of ∼10 ms per particle. Complementary measurements by
Raman and synchrotron XRD are in excellent agreement with the classifications
made by SHG, with measurement times of ∼1 min and several seconds
per particle, respectively. Coupling these capabilities with at-line
monitoring may enable real-time feedback for reaction monitoring during
pharmaceutical production to favor the more bioavailable but metastable
Form I with limits of detection in the ppm regime
Triboluminescence from Pharmaceutical Formulations
Triboluminescence
(TL) is shown to enable selective detection of
trace crystallinity within nominally amorphous solid dispersions (ASDs).
ASDs are increasingly used for the preparation of pharmaceutical formulations,
the physical stability of which can be negatively impacted by trace
crystallinity introduced during manufacturing or storage. In the present
study, TL measurements of a model ASD consisting of griseofulvin in
polyethylene glycol produced limits of detection of 140 ppm. Separate
studies of the particle size dependence of sucrose crystals and the
dependence on polymorphism in clopidogrel bisulfate particles are
both consistent with a mechanism for TL closely linked to the piezoelectric
response of the crystalline fraction. Whereas disordered polymeric
materials cannot support piezoelectric activity, molecular crystals
produced from homochiral molecules adopt crystal structures that are
overwhelmingly symmetry-allowed for piezoelectricity. Consequently,
TL may provide a broadly applicable and simple experimental route
for sensitive detection of trace crystallinity within nominally amorphous
materials