Quantitative Application of in Situ ATR-FTIR and Raman Spec Presentation

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Quantitative Applicationof in Situ ATR-FTIR and

Raman Spectroscopy inCrystallization ProcessesMinas AbuelgasimAbdulramman Makkieh

Nomsey Para-Mallam


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Thorough understanding of the physical andchemical phenomena in pharmaceuticaloperations.

v Solid phase composition can be assessed in situ via characterisationtechniques e.g.

Introduction

PowderX-ray

diffraction Near IR

RamanSpectrosc

opy

Attenuat

ed TotalReflectance


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This investigation dealtwith multicomponentmultiphase processes

such as crystallizationand precipitation forwhich obtaining reliableand robust real-time

information ischallenging

q Particle sizeq

Particle shapeq Suspension densityq Solute concentrationq Temperature


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Two known polymorphs of L-glutamic acid:

Metastable -polymorph Thermodynamically stable -polymorph

The experiments were performed in twojacketed glass reactors of 100 and 500ml.

1 Raman immersion probe inserted into the 100mlreactor

The 500ml reactor contained the ATR-FTIR, Raman andFRBM (Focused Beam Reflective Measurements) probes

Experimental section


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Offline characterisationtechniques

Diffraction patterns were

selected at 2 2-45o witha step size of 0.02o and ascan speed of 0.4o/min.

Multivariate data analysis

Model used to relate themeasured dependentvariables (absorbance) toindependent variables(concentration) wherequalitative measurementsare employed.Mathematics and statistics

Typically, spectra data for n (samples) and m (variables) arecollected in what is referred to as the matrix X(n+m). Lambert-

Beer law assumes a linear dependence for IR absorbance onsolute concentration while typically a multiple linear regressionmodel (MLR) is expressed as:

y = Xb + eUnknownvariable

MatrixXRegressionvector


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ATR-FTIR

Has been applied to monitor liquid-

phase composition.

The decomposition techniques such

as PCR and PLSR were used.

Two different characteristic peaks

were selected at 1354 and 1408 cm

Results and discussion


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Solubility curve measurement

Results and discussion


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Cooling Crystallisation

Figure (a) shows the concentration profiles as a function of thetemperature. For higher cooling rate higher concentration and supersaturation were achieved.

Figure (b) shows the concentration profile as a function of time. Theachieved super saturation increased with increasing cooling rate andsuper saturation was gradually consumed when the final temperaturewas reached and maintained.


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Initial concentration was estimated correctly.- crystals were sticking to the ATR probe.

There was solid interference for both seeded andunseeded polymorph transformation experiments.

Cleaning the probe window as soon as the presence of

solid is detected in the IR spectrum is a solution, but itis the only for relatively short experiment. However forlonger experiments this is not feasible approach.

Polymorph transformation


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Raman Spectroscopy: QualitativeApplication

The time-resolved Raman spectra in the

characteristic range are displayed for aseeded

and unseeded transformation ( samephenomena after nucleation of the R formand

depletion of super saturation)* Signal intensity decreases during the

transformation, indicating that more processvariables than the suspension density only

Results and Discussion


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Raman Spectroscopy: QuantitativeApplication

* During the first 30 min of unseededtransformation experiment ,the solute concentration remains constant; this

period is the induction period during whichnuclei form and grow to a detectible size.* For both polymorphic transformations, theabsolute solid concentration can easily be

obtained through an overall mass balance


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The onset of particleformation


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Quantitative application of in situ ATR-FTIRand Raman spectroscopy using multivariatedata analysis techniques in the case ofmultiphase crystallization and precipitation

processes under non-steady-state conditions.In situ ATR-FTIR spectroscopy has been

applied to monitor the liquid compositionquantitatively. The best model was obtained

by multivariate analysis of ATR-FTIR datawhich is still of great importance for anaccurate in situ measurement of the liquidphase composition although some obstacles

were there.

Conclusion

Quantitative Application of in Situ ATR-FTIR and Raman Spec Presentation

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