Instrumentation & Measurement Magazine 24-5 - 38

The STC consists of a 1 L jacketed glass flask with a built-in
stirring system. The temperature inside the flask is measured
by a thermometer and controlled by a water-cooling bath circulating
in the jacket. The concentration of paracetamol in the
mother liquor is measured by the refractometric sensor. The
experimental setup is presented in Fig. 2a.
A 200 g/kg solution of paracetamol in 40% (v/v) ethanol/
water was stirred at 150 rpm and kept at 45 °C. The temperature
of the solution gradually decreased when the temperature
of the cooling bath was reduced to 25 °C. When the temperature
of the solution reached 25 °C, seeds of paracetamol were
introduced. The addition of seeds prevented the formation
of crystals on the surface of the refractometric sensor, which
could interfere with the signal measured by the sensor.
The experimental setup of the OFC is presented in Fig. 2b.
The OFC was constructed with three plates: one Teflon plate
at the base, one Teflon plate at the middle, and one polycarbonate
plate at the top. In the middle plate, two channels were
carved: one channel designed with smooth periodic constrictions
at the top where the crystallization takes place and a
straight channel at the base where the water of a cooling bath
circulates. The channel where the crystallization takes place
comprises a volume of ~70 mL. Besides its optimized geometry,
the OFC also has optimum dimensions that assure the
reduction of waste and reagents requirements during the crystallization
process [12].
Initially, the OFC was filled with ethanol and thermostated
at 25 °C. The frequency and the amplitude of
oscillation were set at 4 Hz and 4 mm (peak-to-peak in the piston),
respectively. Then, a 200 g/kg solution of paracetamol
in 40% (v/v) ethanol/water at 45 °C was fed into the OFC by
a peristaltic pump (BT300-2J, supplied by Longer Pump) at
40 mL/min. The solution became supersaturated due to the
decrease of temperature, which provided the driving force
required for crystallization. The crystals of paracetamol were
then collected at the end of the OFC. The concentration of
paracetamol was measured by two refractometric sensors,
placed at the input and the output of the OFC system as it is
identified in Fig. 2b.
Results and Discussion
Calibration Curve
The concentration of the standard solutions of paracetamol
increases from 53 to 261 g/kg, which leads to the increase of
optical density of solutions. This variation corresponds to a refractive
index variation in a range from 1.3634 RIU to 1.3947
RIU.
Fig. 3 presents the optical power response of the refractometric
sensor and its correlation to the refractive index
and concentration of the measured standard solutions. This
response was obtained with a sensitivity to paracetamol
refractive index of - 1.53×10- 2
lution of 5.06×10- 4
± 0.05×10−2
(RIU/dB) and a resoRIU,
which corresponds to a concentration
sensitivity of -101.7 ± 3.58 ((g/kg)/dB) and a resolution of 3.36
Kg/g, respectively.
38
Fig. 4. Paracetamol concentration during crystallization in the STC. (Inset:
Evolution of the optical power during crystallization).
IEEE Instrumentation & Measurement Magazine
August 2021
Fig. 3. Paracetamol concentration as a function of the optical power. (Inset:
Refractive index of each paracetamol standard solutions as a function of the
optical power).
As expected, the optical power decreased as the refractive
index and the concentration increased, which is justified
by the decrease of the amplitude of the reflected light at the fiber/liquid
interface. Since the optical power measured by the
refractometric sensor varies linearly with the concentration
within the range of concentrations under study, a concentration
versus optical power calibration curve could be used to
monitor the concentration of paracetamol in the crystallizers.
Stirred Tank Crystallizer
The refractometric sensor monitored the evolution of the
optical power during crystallization in the STC. Then, the concentration
of paracetamol in the mother liquor was calculated
from the calibration curve, as shown in Fig. 4.
Initially, the sensor measures a concentration close to 200
g/kg when paracetamol is fully dissolved. When the seeds
are introduced, there is a slight increase of concentration due
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