Chemistry Reference
In-Depth Information
while keeping the library plate in the horizontal position has been designed [37].
Figure 11.11 is a picture of a Bruker D8 Discover GADDS HTS (high-throughput
screening). The system can run at an optimum configuration for both reflection (a) and
transmission (b) modes while keeping the material library plate in the horizontal
position. In reflection mode (a) both the X-ray source/optics assembly and 2D detector
are on the same side (top) of the material library plate. The switch from reflectionmode
to transmission mode is simply done by driving the X-ray source and optics assembly
from the same side (top) of the sample plate to the opposite side (bottom).
11.3 COMBINED SCREENING WITH XRD
2
AND RAMAN
Combinatorial screening with two-dimensional X-ray diffraction can be combined
with other material characterization techniques. One example is to combine XRD
2
and Raman spectroscopy. Unlike most analytical techniques, both X-ray diffraction
and Raman spectroscopy are nondestructive methods that require virtually no sample
preparation, thus allowing samples to be analyzed simply and quickly in their natural
form. These two techniques are also complementary to one another in that X-ray
diffraction provides abundant information on the atomic arrangement of the sample
revealed through the diffraction pattern, and Raman spectroscopy can measure the
characteristic vibration frequencies determined by the chemical composition and
chemical bonds [38,39]. For crystal form analysis in pharmaceutical research, the
primary technique is X-ray diffraction, since it is directly related to the crystal
structure. Ideally, the effective diffraction volume should cover some 10
8
-10
10
crystallites with completely random orientation. However, in some cases it is very
difficult to distinguish two crystal forms when they have very similar diffraction
patterns due to preferred orientations and poor sampling statistics associated with a
small amount of sample on the library plate. In these cases, cluster analysis based
solely on XRD data may not be able to distinguish between relative intensity changes
due to crystal structural changes and changes due to preferred orientation, crystal size,
or even instrument alignment error, while Raman spectroscopy, or other vibration
spectroscopy techniques (FTIR, NIR, etc.), may be able to distinguish the crystal
forms without ambiguity [40].
As complex composite systems require sophisticatedmodeling to separate chemical
and physical features, no single technique has proven tobe universally applicable to suit
all the analytical needs of pharmaceutical manufacturing and characterization [41].
Combinatorial screening based on spectroscopic and diffraction techniques is of high
importance for drug substances and formulations since the polymorphism of active
ingredients has to be controlled to achieve a reliable product quality that will satisfy
regulatoryauthorities. Inpatent applications, twoormore independent techniquesmore
likely to uniquely identify a particular solid form than one technique. For instance, the
claims of a cocrystal describe it as having XRPD peaks at approximately 10.6
and
12.1
2u and Raman peaks at about 735 cm
1
and approximately 809 cm
1
[42].
Figure 11.12 is a picture of a combinatorial screening system (Bruker AXS
D8 ScreenLab) consisting of a two-dimensional X-ray diffractometer, Raman
