The practical exercise will take place in groups of 4/5
students and will extend over 4 lab sessions.
Each week there will be a workshop to in which you will be supported in
analysing your data and planning your lab time.
You will produce an individual
report which is in the style of an
industrial report. Assessment of this
report will contribute 40% of the module mark.
The deadline for submission is 2nd
December 2019. Below is the brief
for the practical exercise and guidelines for the content and structure of the
The Drug Discovery Group in your company have isolated
several new candidate materials which may be developed to treat inflammatory
conditions. These have been passed to
the Solid State Group to determine its properties. Working in groups of five, you will be given
a sample of a candidate drug and will carry out a screen of its solid state
chemistry identifying and characterising as many solid forms as possible.
For the sample provided
Measure its X-ray powder diffraction pattern.Investigate thermal behaviour using DSC, TGA and
hotstage microscopy. You may use some or all of these techniques as
appropriate.Measure its infra-red spectrum and identify the
main functional groups.Using the data collected identify the sample as
an anhydrous material, hydrate or solvate, or salt
For the solid state screen
Recrystallize your material from up to two
organic solvents and from water.You will need to do a rough determination of the
solubility in each of the solvents you choose.
For ONE of the solvents, you should do an
accurate determination of solubility using UV/VIS spectroscopy. For one of your solvents you should slurry the
solid in an organic solvent over an extended period. (1 -2 weeks)For each sample obtained you should measure its
X-ray powder diffraction pattern. Using this data, determine whether the sample
is the same as that provided or a different solid form. For each unique
sample isolated, investigate its thermal behaviour using DSC, TGA and hotstage
microscopy. You may use some or all of these techniques as appropriate.For each unique sample obtained measure the
infra-red spectrum and identify the main functional groups.If polymorphs are observed you should attempt to
identify the thermodynamically stable polymorph.
You should evaluate the data obtained and present a report
detailing how many solid forms of the drug candidate you have obtained. You should include any information on the
relative stability of any polymorphs observed.
Presentation of Report for
Polymorph Screen: Guidance notes
The results of your solid state
screening should be presented in the style of an Industrial report. These notes give you information on what
should be included and how to lay out the report.
Names of other
group members: suraj, mattew, and pradeep
Candidate Drug: AXT
Total no of
unique solid forms identified: hydrate, anhydrate
summary ( ½ page) 10%
stating the number of unique solid forms obtained.
statement of what these are (e.g. two polymorphs and a hydrate)
description of methods of preparation (e.g. Form A obtained by recrystallisation
from acetone, Form B obtained by heating of Form A and the hydrate obtained by
storing Form A in a humid atmosphere).
information on stability (e.g. Form B converts to Form A at room temperature
over a period of several days)
Any other info
such as different morphologies observed.
characterisation not carried out e.g. Raman spectroscopy was not carried out
ambiguities, further work needed or other important information.
of solid forms obtained 20%
For each solid form isolated
provide the brief outcomes of the characterisation. Some example information is provided to help
2A. Form A:
Method of preparation
drug powder was dissolved in 40ml of acetone at 35°C and stirred using a
magnetic stirrer for 30 min. The
solution was cooled slowly to room temperature and after around 10 min elongated
needle-like crystals were produced.
These were collected by Buchner filtration and dried in an oven at
40°C. Recrystallisation from methanol
yielded the same material.
Peaks at 10,
25, 32, 48 and 54 °2q. PXRD pattern shown in Figure A1.
from room temperature at 10°min-1, the sample showed a broad
exothermic peak at 122-4° and a sharp exotherm at 157°C (shown in Figure
A2). TGA indicated no loss of mass at
these temperatures and hotstage microscopy indicated that a polymorphic phase
transformation began at 122°C indicated by a change of colour of the crystals
and the observation of cracks appearing (Figure A3). The sample was observed to melt at 157-8°C
IR (significant peaks)
Give detail of main
peaks and possible assignment to chemical class. Show IR spectrum.
in acetone 0.2g ml-1, (see figure A5 for calibration graph). Also soluble in methanol and water (
approx. 0.4gml-1 and o.8gml-1 respectively)
Nature of Solid form
of candidate 6008PB-2015
and discussion of evidence 30%
Detailed interpretation of experimental evidence obtained
and how this supports the characterisation presented e.g. how can you be sure
that Form A and Form B are different polymorphs and not solvates? Can you say which is most thermodynamically
stable and what is the evidence for this?
Discuss all available data for a sample, and compare and contrast
information obtained from each technique.
Solubility calibration graph for accurate determination
should also be presented, along with calculations.
Characterisation required 30%Discuss what further work would be needed to
complete the analysis or remove any ambiguity.
This could be repeating your experiment trying different solvents or
heating rates etc. Give detail of any
tests not performed, either due to time constraints, availability of material
or other factors. Describe what additional analysis should be done
for a full understanding of the solid state chemistry of the material. Assume that you have access to any technique
that would be useful. Discuss what
information you might expect to obtain from further study.
experimental methods: 10%
Details of general methods such as DSC providing
instrumental information such as make and model number. Standard procedures such as sample prep and
calibration routines. Standard method
details where these were generally applied such as heating rates and
temperature ranges. Variations to
standard procedures should be included in the detailed proforma for the
appropriate solid form.
General methods for all characterisation techniques should
Executive summary ( ½ page) 10%Summary of solid forms obtained 20%Presentation and discussion of evidence 30%Further Characterisation required 30%General experimental methods: 10%
The post Solid state characterisation of candidate drug
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