Analytical Techniques for Characterization of Solid State
-
Upload
ramzsingh90 -
Category
Documents
-
view
218 -
download
0
Transcript of Analytical Techniques for Characterization of Solid State
-
7/31/2019 Analytical Techniques for Characterization of Solid State
1/49
Submitted by :-Ramneek Singh
-
7/31/2019 Analytical Techniques for Characterization of Solid State
2/49
Polymorphism - the ability ofa compound to crystallise inmore than one crystal form
Pseudopolymorphic forms
(solvated forms) - crystallinesolids containing solventmolecules as an integral partof their crystal structure
Amorphism - the absence of
regular or crystalline structurein a body solid; amorphousmaterials do not possessthree-dimensional long-rangemolecular order
Polymorph A Polymorph B
Solvate A Solvate B
-
7/31/2019 Analytical Techniques for Characterization of Solid State
3/49
Verifying that the solid is the expectedchemical compound.
Characterizing the internal structure. Describing the habit of the crystal.
Therefore , comprehensive characterization of all
preformulation bulk lots is necessary to avoid
misleading prediction of stability or solubility , which
depends on a particular crystalline form .
-
7/31/2019 Analytical Techniques for Characterization of Solid State
4/49
Active pharmaceutical ingredients (API, drugs) Mainly solids (crystalline, amorphous or semi-
crystalline)
Organic molecules, peptides, proteins Single components
Excipients (additives, fillers etc.) Organic, inorganic
Solids or liquids
Formulations (dosage forms, delivery systems) Mixtures of APIs and excipients
Packaging materials
-
7/31/2019 Analytical Techniques for Characterization of Solid State
5/49
1.Bulk and Biopharmaceutical PropertiesFlowability, CompressabilitySolubility and dissolution (Bioavailability)
2.Chemical PropertiesStability / Reactivity
3.Regulatory issuesQuality, Efficacy and Safety
4.Intellectual Property
Patents.5.Processing factorsBulk and mechanical propertiesEase of isolation, filtration and dryingDegree of purity
-
7/31/2019 Analytical Techniques for Characterization of Solid State
6/49
For thermodynamic properties:1. Thermal analysis
2. Microcalorimetry3. Vapour pressure determination4. Solubility determination
For particle and bulk properties:1. Microscopy
2. Micromeritics
-
7/31/2019 Analytical Techniques for Characterization of Solid State
7/49
For structural properties:1. X-ray diffraction method
powdersingle crystal2. Spectroscopy
UV
IRRamanSolid state NMR
-
7/31/2019 Analytical Techniques for Characterization of Solid State
8/49
-
7/31/2019 Analytical Techniques for Characterization of Solid State
9/49
IUPAC definition - a group of techniques in which aphysical property is measured as a function oftemperature, while the sample is subjected to a
controlled temperature programme (heating, coolingor isothermal). A range of techniques e.g.: Differential Thermal Analysis (DTA) temperature
Differential Scanning Calorimetry (DSC) energy
Thermogravimetric Analysis (TGA) mass
Thermomechanical Analysis (TMA) dimensions
Dielectric Analysis (DEA) dielectric/electric properties
-
7/31/2019 Analytical Techniques for Characterization of Solid State
10/49
Modern instrumentation used for thermal analysisusually consists of the following parts:
sample holder/compartment for the sample
sensors to detect/measure a property of the sample andthe temperature
an enclosure within which the experimental parameters
(temperature, speed, environment) may be controlled a computer to control data collection and processing
sample
sensors
temperaturecontrol (furnace)
PC
-
7/31/2019 Analytical Techniques for Characterization of Solid State
11/49
Most popular thermal technique DSC measures the heat absorbed or liberated during
the various transitions in the sample due totemperature treatment Differential: sample relative to reference Scanning: temperature is ramped Calorimeter: measures heat
DSC measurements are both qualitative and
quantitative and provide information about physicaland chemical changes involving: Endothermic processes sample absorbs energy Exothermic processes sample releases energy Changes in heat capacity
-
7/31/2019 Analytical Techniques for Characterization of Solid State
12/49
Power Compensation DSC
High resolution / high sensitivity research studies Absolute specific heat measurement Very sensitive to contamination of sample holders
Heat Flux DSC
Routine applications Near / at line testing in harsh environments Automated operation
Cost-sensitive laboratories
-
7/31/2019 Analytical Techniques for Characterization of Solid State
13/49
Melting points crystalline materials Desolvation adsorbed and bound solvents Glass transitions amorphous materials
Heats of transitions melting, crystallisation Purity determination contamination,
crystalline/amorphous phase quantification Polymorphic transitions polymorphs and
pseudopolymorphs Processing conditions environmental factors Compatibility interactions between components Decomposition kinetics chemical and thermal
stability
-
7/31/2019 Analytical Techniques for Characterization of Solid State
14/49
40 60 80 100 120 140 160 180 200 220 240 260 280 300
20
mW
temperature [oC]
^exo
Exothermic upwardsEndothermic downwards
Y-axis heat flow
X-axis temperature (and time)
DESOLVATIONGLASS TRANSITION
CRYSTALLISATIONMELTING
DECOMPOSITIONH2O
-
7/31/2019 Analytical Techniques for Characterization of Solid State
15/49
40 60 80 100 120 140 160 180 200 220 240 260 280 300
20
mW
^exo
temperature [oC]
DSC scan of a crystalline material one polymorphic form
MELTING
Onset = melting point (mp)
Heat of fusion (melting) = integration of peak
-
7/31/2019 Analytical Techniques for Characterization of Solid State
16/49
40 60 80 100 120 140 160 180 200 220 240 260 280 300
20
mW
temperature [oC]
^exo
DSC scan of a crystalline material polymorphic transition
METASTABLEFORM
TRANSITION
STABLEFORM
-
7/31/2019 Analytical Techniques for Characterization of Solid State
17/49
40 60 80 100 120 140 160 180 200 220 240 260 280 300
20
mW
^exo
temperature [o
C]DSC scan of a hydrate
MELTING
DEHYDRATION
-
7/31/2019 Analytical Techniques for Characterization of Solid State
18/49
40 60 80 100 120 140 160 180 200 220 240 260 280 300
temperature [C]
1 mW
DEHYDRATION
GLASS TRANSITION
Midpoint = glass transition (Tg)
Polyvinylpyrrolidone (PVP) co-processed with hydroflumethiazide
-
7/31/2019 Analytical Techniques for Characterization of Solid State
19/49
Purity of phenacetin Source: TA Instruments, Cassel RB,Purity Determination and DSC Tzero Technology
-
7/31/2019 Analytical Techniques for Characterization of Solid State
20/49
Source: Schmitt E et al.Thermochim Acta 2001, 380 , 175 183
-
7/31/2019 Analytical Techniques for Characterization of Solid State
21/49
Conventional linear temperature (cooling,heating) programme
Fast scan DSC very fast scan rates (also linear)
MTDSC (modulated temperature DSC) morecomplex temperature programmes, particularlyuseful in the investigation of glass transitions(amorphous materials)
HPDSC (high pressure DSC) stability of materials,oxidation processes
-
7/31/2019 Analytical Techniques for Characterization of Solid State
22/49
Pharma applications:
Enhanced analysis of polymorphism
Detection of low level amorphous content Suppression of decomposition true melting
points
Detection of low energy transitions
Characterisation close to processing conditions
Separation of overlapping events
-
7/31/2019 Analytical Techniques for Characterization of Solid State
23/49
This technique uses composite heating profile: determines heat capacityand separates heat flow into the reversible and non-reversiblecomponents
Benefits
Increased sensitivity for detecting weak transitions especially glasstransition
Separation of complex events into their:
heat capacity (reversible) e.g. glass transition, melting and
kinetic components (non-reversible) e.g. evaporation,crystallization, decomposition
Disadvantages
Slow data collection
Risk of sample transformation
-
7/31/2019 Analytical Techniques for Characterization of Solid State
24/49
A technique measuring thevariation in mass of a sampleundergoing temperaturescanning in a controlled
atmosphere Thermobalance allows for
monitoring sample weight asa function of temperature
The sample hangs from thebalance inside the furnaceand the balance is thermallyisolated from the furnace
balance
sample
furnacepurge gas
-
7/31/2019 Analytical Techniques for Characterization of Solid State
25/49
Desolvation adsorbed and bound solvents,
stoichiometry of hydrates and solvates
Decomposition chemical and thermal stability
Compatibility interactions between components
-
7/31/2019 Analytical Techniques for Characterization of Solid State
26/49
0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320
2
mg
temperature [oC]
TGA curves of crystalline and amorphous substance
-
7/31/2019 Analytical Techniques for Characterization of Solid State
27/49
0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 3400
^exo
20
mW
temperature [oC]
2
mg
DSC and TGA scans of lactose monohydrate
-
7/31/2019 Analytical Techniques for Characterization of Solid State
28/49
Anhydrous/dihydrate mixture was prepared by dry blending. Heating rate was 50/min
-
7/31/2019 Analytical Techniques for Characterization of Solid State
29/49
Thermal techniques alone are insufficient to provethe existence of polymorphs and solvates
Other complementary techniques are used e.g.
microscopy, diffraction and spectroscopy Types:
DSC-TGA
DSC-XRD DSC coupled with X-ray diffraction
TGA-MS TG system coupled with a mass spectrometer
TGA-FTIR TG system coupled with a Fourier Transform
infrared spectrometer
TGA -MS or -FTIR - evolved gas analysis (EGA)
-
7/31/2019 Analytical Techniques for Characterization of Solid State
30/49
All substances that are transparent ,when examinedunder a microscope that has crossed polarizing filters
are either
Isotropic -Which have a single refractive index, thesedo not transmit light and they apper black
(amorphous ,supercooled glasses and non crystalline
or cubic crystal lattice substance ).
Anisotropic -Which have more than one refractiveindex and appear bright with brilliant colors
(birefringence) against the black polarized light.
-
7/31/2019 Analytical Techniques for Characterization of Solid State
31/49
-
7/31/2019 Analytical Techniques for Characterization of Solid State
32/49
-
7/31/2019 Analytical Techniques for Characterization of Solid State
33/49
-
7/31/2019 Analytical Techniques for Characterization of Solid State
34/49
-
7/31/2019 Analytical Techniques for Characterization of Solid State
35/49
Owing to the many possible crystal habitsand their appearances at different
orientations , these methods require a well-trained optical crystallographer tocharacterize fully even simple biaxialsystems.
-
7/31/2019 Analytical Techniques for Characterization of Solid State
36/49
Is arguably an irreplaceable tool for the analysisof pharmaceutical solids and widely-recognizedas the most powerful technique when structural
characterization and identification of crystallinephases (e.g., polymorphs, solvates) is needed. Unlike other analytical techniques with limited
potential for structure characterization and phaseidentification, X-ray diffraction provides an
unparalleled access to the intimate building ofthe crystalline motif, which makes it the mostreliable tool for crystal form identification.
-
7/31/2019 Analytical Techniques for Characterization of Solid State
37/49
X-rays are diffracted by crystals just as visiblelight is dispersed into a color spectrum by a ruledgrating.
This is due to the fact that X-rays havewavelengths of about the same magnitude asthe distance between the atoms or molecules.
X-ray source is hot cathode tube with either amolybdenum anode or copper anode.
-
7/31/2019 Analytical Techniques for Characterization of Solid State
38/49
sin2dn
Braggs equation assumes:
Crystal is perfect and infinite
Incident beam is perfectly parallel and monochromatic
Braggs Equation:-
Where n= any positive integer
d=interplanar distance
-
7/31/2019 Analytical Techniques for Characterization of Solid State
39/49
39
X-ray
intensity(fromdetector)
c
dn
2sin c
Measurement of critical
angle, c, allowscomputation of planar
spacing, d.
Incoming X-rays diffract from crystal planes.
reflections mustbe in phase fora detectable signal
spacingbetweenplanes
d
extradistance
travelledby wave 2
-
7/31/2019 Analytical Techniques for Characterization of Solid State
40/49
determination of bond angles and inter-atomic
distances.
study of crystallattice by diffraction angles.
-
7/31/2019 Analytical Techniques for Characterization of Solid State
41/49
Schematic of 4-circle diffractometer; theangles between the incident ray, thedetector and the sample.
-
7/31/2019 Analytical Techniques for Characterization of Solid State
42/49
Film may be replaced with detector
POWDER METHOD
Different cones for different reflections
-
7/31/2019 Analytical Techniques for Characterization of Solid State
43/49
Is characterization technique for understandingthe nature and the effect of water (or solvent)activity on solids (e.g., bound/non-bound water,hygroscopicity, solvation, phase transition,
wettability, etc.). Vapor sorption kinetics measurements are used
in establishing handling and/or processingconditions for sensitive APIs, excipients and drug
products. In a similar approach, the design ofpackaging materials can benefit from themoisture vapor transmission rate (MVTR) datagenerated using this analytical technique.
-
7/31/2019 Analytical Techniques for Characterization of Solid State
44/49
-
7/31/2019 Analytical Techniques for Characterization of Solid State
45/49
Spectroscopy displays the short-range structureof molecular solid (electronic environment ofmolecular function) and is thus complementary
to long range structural information obtainedfrom X-rays diffractometery. Various techniques used are :-
Raman (regular and micro) FTIR (transmission, reflection, micro) UVIS LiquidNMR(1H, 13C, 15N, 19F, 27Al, 29Si,31P, 51V, 59Co, 63Cu
, 77Se, 113Cd, 195Pt, two dimensional NMR) Solid state NMR (13C, 23Na, 27Al, 29Si, 31P,195Pt)
-
7/31/2019 Analytical Techniques for Characterization of Solid State
46/49
For characterization of solid materials With respect to the structural information
solid state NMR techniques probe the
local environment around a specificnucleus.
Thus, such methods can be used for thedetermination of the local order in solidmaterials. This is particular importance foramorphous materials where othermethods quite often fail.
-
7/31/2019 Analytical Techniques for Characterization of Solid State
47/49
=54.74
B0
In solid state NMR, we tilt the sample to themagic angle, which is 54.74 relative to B0.
And then we spin it around that angle at very high
frequency. Thus the name of this type of NMR Magic Angle Spinning.
-
7/31/2019 Analytical Techniques for Characterization of Solid State
48/49
APPLICATIONS:
Identification of crystal forms based on their individual
chemical shifts.
Determination of phase purity.
Information about structural charecteristics in crystalforms.
Detection of solvent present in solvates and itsinteraction
with lattice.
Analysis of molecular mobility in crystal forms.
-
7/31/2019 Analytical Techniques for Characterization of Solid State
49/49