crystals

Article
Determination of the Nucleation and Growth Kinetics
for Aqueous L-glycine Solutions from the Turbidity
Induction Time Data
Lie-Ding Shiau 1,2
1 Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan 333, Taiwan;
shiau@mail.cgu.edu.tw
2 Department of Urology, Chang Gung Memorial Hospital Linkou, Taoyuan 333, Taiwan




Received: 22 September 2018; Accepted: 23 October 2018; Published: 24 October 2018


Abstract: As the turbidity induction time measurements are influenced by the size distribution of the
nuclei at the detection point, these data should provide important information on both nucleation
and growth. A model is developed in this work to determine the nucleation and growth kinetics of
aqueous L-glycine solutions using the turbidity induction time data for various supersaturations from
293.15 K to 313.15 K. The photomicroscopic growth experiments of aqueous L-glycine solutions are
also conducted to determine the growth kinetics of nuclei under the same conditions for comparison.
The results indicate that the interfacial energy obtained from this model is consistent with that
obtained based on the traditional method by assuming ti −1 ∝ J. The growth kinetics, including
the growth activation energy and the kinetic growth parameter, obtained from this model using
the induction time data are close to those obtained from the photomicroscopic growth experiments
performed in this work.

Keywords: crystallization; nucleation; induction time; interfacial energy

1. Introduction
According to classical nucleation theory (CNT), only nuclei greater than a critical nucleus size
are thermodynamically stable and can continue to grow to a detectable size [1–3]. The formation of
critical nuclei is closely related to the interfacial energy of the crystallized substance, which is usually
calculated from the induction time data in the literature [4–10].
The induction time is defined as the elapsed time between the creation of the supersaturation and
the appearance of detectable nuclei at a constant temperature. Although the induction time can be
detected by visual observation of the crystal’s appearance [7,11], turbidity measurements have been
commonly adopted in recent years to determine the induction time by detecting the change in the
intensity of transmitted light in solution at the onset of nucleation [12–17]. Traditionally, determination
of the interfacial energy from the induction time data is often simplified by assuming ti −1 ∝ J [1,4–10].
Thus, it is implicitly assumed that at the detection of the nucleation point, only the number of the
nuclei is accounted for regarding the change in the intensity of transmitted light in solution.
The detection of nucleation point based on turbidity measurements should be influenced by both
the number and the size of the nuclei [18] as the change in the intensity of transmitted light in solution
is proportional to the size distribution of the nuclei instead of the number of the nuclei. To incorporate
the effect of the nuclei size distribution on the detection of nucleation, Shiau and coworkers [18,19]
have developed a model to examine the turbidity induction time data of aqueous L-glutamic acid
solutions using the L-glutamic acid growth kinetics reported by Scholl et al. [20]. It is found that the
obtained interfacial energy and growth activation energy of L-glutamic acid [19] are consistent with

Crystals 2018, 8, 403; doi:10.3390/cryst8110403 www.mdpi.com/journal/crystals

Crystals 2018, 8, 403 2 of 14

the literature data. L-glycine is the simplest amino acid and is often used as a model compound in
the study of solution nucleation [21–25]. The objective of this work is to develop a model to study
the nucleation and growth of aqueous L-glycine solutions based on the turbidity induction time data.
To validate the obtained L-glycine growth kinetics from this model, the photomicroscopic growth
experiments of aqueous L-glycine solutions are also conducted to determine the growth kinetics of
nuclei at the same conditions for comparison.

2. Theory
The nucleation rate based on CNT [1–3] is expressed as:

16πv2 γ3
J = A J exp(− ), (1)
3k B 3 T 3 ln2 S

where v = ρMNW and S = CCeq . For simplicity, the nucleation event is assumed to correspond to a point
C A
at which the total number density of the nuclei has reached a fixed (but unknown) value, fN [26,27].
One obtains at the induction time ti using:

f N = J ti , (2)

Thus, it is implicitly assumed that the detection of the nucleation point is related to the number of
nuclei. Substituting Equation (1) into Equation (2) yields:

16πv2 γ3
   
1 AJ
ln = ln − , (3)
ti fN 3k B 3 T 3 ln2 S

This is consistent with the common method adopted in the literature to calculate γ from induction
time data [1,4–10].
The turbidity induction time measurements are based on the change in intensity of transmitted
or scattered light along the detector direction, which should be related to the size distribution of the
nuclei instead of the number of the nuclei at the detection point [18,19]. As nuclei are progressively
generated during the induction time period (t = 0–ti ), the nuclei born in the earlier stage will grow to a
greater size than those born in the later stage at ti . To incorporate the effect of crystal growth at the
nucleation point, Shiau and Lu [18] proposed a model to correlate the nucleation and growth with
the turbidity induction time data using the predetermined growth kinetics. However, as it is often
difficult to experimentally measure the growth kinetics of small nuclei, the application of this model
is restricted.
As the turbidity induction time measurements are influenced by the size distribution of the
nuclei, these data should provide important information on both nucleation and growth. A model is
developed in the following to investigate the nucleation and growth of nuclei based on the turbidity
induction time data without the predetermined growth kinetics. In the derivation, a simple empirical
power-law growth rate is proposed as:

G = k G ( S − 1) g , (4)

where the value of g mostly falls between 1 and 2. Based on Burton–Cabrera–Frank (BCF) growth
theory [28–30], the value of g is found close to 2 for low supersaturations [31]. Mohan and Myerson [32]
indicated for aqueous L-glycine solutions at 293.15 K that Equation (4) with g = 2 is consistent with the
BCF growth kinetics reported by Li and Rodriguez-Hornedo [33].
In the induction time study, nuclei born at any time t (0 < t < ti ) can grow from t to ti and their
size at time ti is:
L ( t ) = G ( ti − t ) (5)
Crystals 2018, 8, 403 3 of 14

The corresponding volume of nuclei with size L at time ti is

V ( t ) = k V L ( t )3 = k V G 3 ( t i − t )3 , (6)

As nuclei are progressively generated from t = 0 to ti , the total volume of all the nuclei per unit
solution volume at time ti is given by:
Z t
i
fV = JV (t)dt, (7)
0

Substituting Equation (6) into Equation (7) yields:

JkV G3 ti 4
Z t
i
f V = JkV G3 (ti − t)3 dt = , (8)
0 4

Note that J and G remain unchanged as S is kept at a particular supersaturation during each
induction time experiment.
Substituting Equations (1) and (4) into Equation (8) with g = 2 leads to:

A J k V k G 3 ( S − 1)6 t i 4 16πv2 γ3
fV = exp(− ), (9)
4 3k B 3 T 3 ln2 S

Rearranging Equation (9) yields:

" # !
4 A J kG 3 16πv2 γ3
ln = ln − , (10)
k V t i 4 ( S − 1)6 fV 3k B 3 T 3 ln2 S
 
4 1
A plot of ln versus at a given temperature should give a straight line, the slope
k V t i 4 ( S −1)6 ln2 S
3
A k
and intercept of which permit determination of γ and Jf G , respectively.
V
The temperature dependence of kG can be expressed in terms of the Arrhenius equation as:

EG
k G = AG exp(− ), (11)
RT
A J kG 3
Once fV is determined at different temperatures, substitution of Equation (11) yields:
! !
A J kG 3 A J AG 3 3EG
ln = ln − , (12)
fV fV RT
 
A J kG 3 1
Thus, a plot of ln fV versus T should give a straight line, the slope and intercept of which
3
A J AG
permit determination of EG and fV , respectively. It should be noted that AJ AG 3 can be determined
if fV is known.

3. Experimental

3.1. Induction Time Measurements

The experimental apparatus of a 250 mL crystallizer was the same as that used by Shiau and
Lu [18]. Deionized water and L-glycine (>99%, Alfa Aesar, Haverhill, MA, USA) were used to prepare
the supersaturated solution. In each experiment, a 200 mL aqueous L-glycine solution with the desired
supersaturation was loaded into the crystallizer. The solution was stirred with a magnetic stirrer
at a constant stirring rate of 350 rpm. A turbidity probe with a Near-Infrared source (Crystal Eyes
Crystals 2018, 8, 403 4 of 14

manufactured by HEL limited, Hertford, UK) was used to detect the nucleation event during the
induction time study. The solution is held at 3 K above the saturated temperature for 5–10 min to
ensure a complete dissolution at the beginning of the experiment, which was also confirmed using
the turbidity measurement. As the cooling rate to reach a particular supersaturation influences the
nucleation induction time [34], the solution was rapidly cooled at 25 ◦ C/min to the desired constant
temperature. Thus, the lag time was usually less than 60 s, which was much smaller than the measured
induction times listed in Table 1. Figure 1 shows the variation of measured turbidity with time for
S = 1.15 and a temperature of 293.15 K. The percentage threshold for the turbidity data was defined as
the change
Crystals inx turbidity
2018, 8, to determine whether a nucleation event had occurred [35]. A setting of4 20%
FOR PEER REVIEW of 14
for the threshold was employed for all the turbidity induction time data in this work.
Table 1. The average induction times and the corresponding standard deviations (SD) for L-Glycine.
Table 1. The average induction times and the corresponding standard deviations (SD) for L-Glycine.
𝑻(𝐊) 𝑺(−) 𝒕𝒊 (𝑺𝑫)(𝐬)
T(K)1.10 S(−) ti (SD)(s) 2120 (471)
1.12 1.10 2120 (471) 1090 (242)
293.15
1.13 1.12 1090 (242) 936 (253)
293.15
1.16 1.13 936 (253) 563 (157)
1.16 563 (157)
1.07 2672 (588)
1.08 1.07 2672 (588) 1390 (276)
303.15 1.08 1390 (276)
1.10
303.15 831 (247)
1.10 831 (247)
1.12 1.12 442 (198) 442 (198)
1.06 2327 (534)
1.06 2327 (534)
1.07 1.07 953 (273) 953 (273)
313.15 313.15
1.08 1.08 737 (201) 737 (201)
1.10 1.10 429 (175) 429 (175)

Figure
Figure 1. The variation
1. The variation of
of measured
measured turbidity
turbidity with
with time for SS =
time for 1.15 and
= 1.15 and 293.15
293.15 K.
K.
3.2. Growth Rate Measurements
3.2. Growth Rate Measurements
The photomicroscopic experiments shown are performed to investigate the growth rates of
The photomicroscopic experiments shown are performed to investigate the growth rates of L-
L-glycine in water. This growth cell shown in Figure 2 [36] has a solution chamber of 20 mL in the
glycine in water. This growth cell shown in Figure 2 [36] has a solution chamber of 20 mL in the upper
upper part and a chamber for temperature-controlled water in the lower part. The growth rates of
part and a chamber for temperature-controlled water in the lower part. The growth rates of aqueous
L-glycine solutions for various supersaturations from 293.15 K to 313.15 K were studied isothermally
in the upper stagnant solution.
Crystals 2018, 8, 403 5 of 14

aqueous L-glycine solutions for various supersaturations from 293.15 K to 313.15 K were studied
isothermally
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REVIEW 5 of 14

Top view Side view

(a)

Top view Side view

(b)
The photomicroscopic
Figure 2. The photomicroscopic growth
growth apparatus
apparatus (a)
(a) the
the real
real picture
picture of growth cell; (b) schematic
diagram
diagram of growth cell with the features: (1) solution chamber; (2) thermistor;
chamber; thermistor; (3) solution
solution inlet and
outlet; (4) constant-temperature water chamber; (5) water inlet and outlet.

The growth
The growth of of crystals
crystals was
was monitored
monitored photographically through aa microscope
photographically through microscope andand analyzed
analyzed
using an image analyzer (Imaging Software, NIS-Elements, Nikon, Japan)
using an image analyzer (Imaging Software, NIS-Elements, Nikon, Japan) to determine the area to determine the area of
of
each crystal. For simplicity, the characteristic
each crystal. For simplicity, the characteristic size of the small crystal is taken as the equivalent
size of the small crystal is taken as the equivalent circular
2 /4, leading to L =
√
diameter, i.e., A = 4A/π.
circular diameter, i.e., 𝐴 = 𝜋𝐿 /4, leading to 𝐿 = 4𝐴/𝜋.
πL The sizes
The were
sizes then
wereplotted against
then plotted time for
against timeeach
for
each crystal with the slope equal to the growth rate. In each run, 8–10 crystals were analyzedthe
crystal with the slope equal to the growth rate. In each run, 8–10 crystals were analyzed to calculate to
mean growth
calculate rate among
the mean growth these
ratecrystals
amongunder
theseeach condition.
crystals under Figure 3 shows the
each condition. photograph
Figure 3 shows of the
the
needle-like α-form
photograph crystals in solution
of the needle-like taken inin
α-form crystals ansolution
experimental
taken run
in an S = 1.12 at T run
forexperimental = 303.15
for S K. It was
= 1.12 at
found for various supersaturations from 293.15 K to 313.15 K that the needle-like α-form
T = 303.15 K. It was found for various supersaturations from 293.15 K to 313.15 K that the needle-like crystals were
nucleated
α-form in thewere
crystals photomicroscopic
nucleated in the experiments.
photomicroscopic experiments.
Crystals 2018, 8, 403 6 of 14
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The photograph
Figure 3. The photograph of
of the
the needle-like
needle-like α-form L-glycine crystals
α-form L-glycine crystals in
in solution
solution taken
taken in the
photomicroscopic experiment at SS =
= 1.12 and 303.15 K.

4. Results
4. Results and and Discussion
Discussion
The induction
The induction time time datadata for for aqueous
aqueous L-glycine
L-glycine solutions
solutions were were measured
measured for for various
various
supersaturations from 293.15 K to 313.15 K. Each run was carried out at
supersaturations from 293.15 K to 313.15 K. Each run was carried out at least three times to determineleast three times to determine
the average
the average induction
induction time time under
under each
each condition.
condition. The The average
average induction
induction times
times and
and thethe corresponding
corresponding
standard deviations
standard deviations (SD) (SD) are
are listed
listed in Table 1.
in Table 1. The
The equilibrium
equilibrium concentration
concentration of of the L-glycine
α-form L-glycine
the α-form
in water was given by C (T) = 5.4397 × 10 −3 T 2 − 3.2022 × 10−1 T − 188.2 (C in kg/m3 , and T in
eq
in water was given by Ceq(T) = 5.4397 × 10−3T2 − 3.2022 × 10−1T − 188.2 (Ceq in kg/m3, and T in K) [37]. eq
K) [37]. Note MWkg/mol, 3 , and ν = 7.757 × 10−29 m3 for L-glycine.
Note that MWthat = 0.075 = 0.075 ρkg/mol, ρC = 1607
C = 1607 kg/m 3, andkg/m
ν = 7.757 × 10−29 m3 for L-glycine.
Although L-glycine can be crystallized in different polymorphs, the
Although L-glycine can be crystallized in different polymorphs, α-form is
the α-form is usually
usually achieved
achieved
from nucleation of pure aqueous solutions [21–25]. To
from nucleation of pure aqueous solutions [21–25]. To validate the polymorphm of validate the polymorphm of the
the L-glycine
L-glycine
crystals, the
crystals, thefinalfinaldried
driedcrystals
crystals at at
thetheendend of induction
of the the induction time time experiments
experiments were analyzed
were analyzed using
using both optical microscopy and Raman spectroscopy (P/N
both optical microscopy and Raman spectroscopy (P/N LSI-DP2-785 Dimension-P2 System, 785 LSI-DP2-785 Dimension-P2 System,
nm,
785 nm, manufactured by Lambda Solutions, INC., Seattle, WA,
manufactured by Lambda Solutions, INC., Seattle, WA, USA). The results all indicated that the USA). The results all indicated
that the needle-like
needle-like α-form α-formcrystalscrystals
were were obtainedobtained
fromfrom aqueous
aqueous L-glycinesolutions
L-glycine solutionsfor for various
various
supersaturations from 293.15 K to 313.15 K. Figure 4 shows the Raman spectra
supersaturations from 293.15 K to 313.15 K. Figure 4 shows the Raman spectra of pure α-form crystals of pure α-form crystals
and product
and product crystals
crystals obtained
obtained at at various
various supersaturations.
supersaturations. As As compared
compared with with the
the Raman
Raman spectra
spectra of
of
pure α-form crystals reported by Murli et al. [38], it was confirmed
pure α-form crystals reported by Murli et al. [38], it was confirmed that α-form crystals werethat α-form crystals were produced
for variousfor
produced supersaturations at 303.15 K.
various supersaturations The section
at 303.15 K. Theofsection
the Ramanof thespectra
Raman of α-, β-,ofand
spectra γ-glycine
α-, β-, and γ-
used for characterization are also depicted by Bouchard
glycine used for characterization are also depicted by Bouchard et al. [39]. et al. [39].
Figure 55 shows
Figure shows thethe measured induction time
measured induction time data
data from
from 293.15
293.15 K K toto 313.15
313.15 K K fitted
fitted to
to Equation
Equation
(3) based
(3) based on
on ff N . The fitted results are listed in Table 2, where γ was in the
N. The fitted results are listed in Table 2, where γ was in the range 1.93–2.37 mJ/m2 and
range 1.93–2.37 mJ/m2
AJ
andwas was
f N in theinrange
the range
4.35 ×4.35 × 10−×3 –6.42
10−3–6.42 10−3 s−1× 10−3 s−1 . the
. Although Although the exact
exact value of AJbe
value only
of AJ could could only be
determined
determined with a known value of fN , γ was not influenced by the chosen value of fN .
with a known value of fN, γ was not influenced by the chosen value of fN.
Table 2. The fitted results of the induction time data to Equation (3) based on fN .
Table 2. The fitted results of the induction time data to Equation (3) based on fN.
AJ −1
T(K) γ(mJ/m2 ) fN𝑨(s ) AJ (m−3 s−1 )
𝑱
𝑻(𝐊) 𝜸(𝐦𝐉/𝐦 ) 𝟐 (𝐬 −𝟏3) 𝑨𝑱 (𝐦 𝟑 𝐬 𝟏 )
293.15 2.37 4.35𝒇𝑵
× 10 3.32 × 109
× 10 −3 109 × 109
4.04 ×3.32
293.15 303.15 2.372.07 5.29
4.35 × 10−3
× 10 − 3 109 × 109
4.91 ×4.04
303.15 313.15 2.071.93 6.42
5.29 × 10−3
313.15 1.93 6.42 × 10−3 4.91 × 109
Crystals 2018, 8, 403 7 of 14
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4. The Raman
Figure 4.
Figure Raman spectra ofof pure α-form
α-form crystals and
and product crystals
crystals obtained in
in the induction
induction
Figure 4.The
The Ramanspectra
spectra ofpure
pure α-formcrystals
crystals andproduct
product crystalsobtained
obtained inthe
the induction
time
time experiments for various supersaturations at 303.15 K.
timeexperiments
experimentsfor
forvarious
varioussupersaturations
supersaturationsatat303.15
303.15K.
K.

Figure
Figure5.5.
Figure The
5.The induction
Theinduction time
inductiontime data
timedata of
dataof L-glycine
ofL-glycine at
L-glycineat 293.15–313.15
at293.15–313.15
293.15–313.15KK fitted
Kfitted to
fittedto Equation
toEquation (3)
Equation(3) based
(3)based on 𝑓f𝑓N...
on
basedon

As the
As the induction time time data are
are measured by the intensity change of the transmitted light, Figure 6
As theinduction
induction timedata data aremeasured
measuredby bythe theintensity
intensitychange
changeof ofthe
thetransmitted
transmittedlight,
light,Figure
Figure
shows
66shows the measured induction time data from 293.15 K to 313.15 K fitted to Equation (10) based on
showsthe themeasured
measuredinduction
inductiontime timedata
datafrom
from293.15 293.15KKto to313.15
313.15KKfitted
fittedto
toEquation
Equation(10) (10)based
basedon on
ffVfVV. ..Note thatggwas
Notethat wasassumedassumedto tobe be22 due due to
to low
low supersaturations
supersaturations (S (S == 1.4–2.4)
Note that g was assumed to be 2 due to low supersaturations (S = 1.4–2.4) in the induction2 time
1.4–2.4) in
in the
the induction
induction time
time
experiments. The
experiments. Thefittedfitted results are
are listed in in Table 3, where γ was in the range 2.49–2.93 mJ/m and
experiments. The fittedresultsresults arelistedlisted inTable
Table3,3,where whereγγwaswasininthetherange
range2.49–2.93
2.49–2.93mJ/mmJ/m2 2and
and
A J kG 3 − 5 − 3 − 4
was
f V was in the range 2.78 × 10 –2.58 × 10 s . It should be noted that γ was not influenced by
wasin inthe
therange
range2.78 2.78××10
10−5−5–2.58
–2.58××10 10−3−3ss−4−4. .ItItshould
shouldbe benoted
notedthat
thatγγwaswasnotnotinfluenced
influencedby bythe
the
the chosen value of fV .
chosen
chosenvalue valueof offVfV. .
 Crystals 2018, 8, 403 8 of 14
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Theinduction
Figure6.6.The
Figure inductiontime
timedata
dataofofL-glycine
L-glycineatat293.15–313.15
293.15–313.15KKfitted
fittedto
toEquation
Equation(10)
(10)based on 𝑓f V. .
basedon

Table 3. The fitted results of the induction time data to Equation (10) based on f V .
Table 3. The fitted results of the induction time data to Equation (10) based on 𝑓 .
AJ kG 3 −4
T(K) γ(mJ/m2 ) f𝑨 (s 𝟑 )
V 𝑱 𝒌𝑮
𝑻(𝐊) 𝜸(𝐦𝐉/𝐦𝟐 ) (𝐬 𝟒 )
293.15 2.93 𝒇𝑽10− 5
2.78 ×
293.15303.15 2.66
2.93 × 10×−410−5
4.152.78
303.15313.15 2.49
2.66 × 10×− 310−4
2.584.15
313.15 2.49 2.58 × 10−3
The turbidity induction time measurements in the current experiments were based on the intensity
change ofturbidity
The induction
the transmitted time
light, measurements
which is related toin fV .the current
Thus, experiments
compared were
to γ based on based on the
fN , γ based on
intensity
fV shouldchange of the transmitted
more accurately represent light,
the which
actual is related toenergy
interfacial fV. Thus, compared Shiau
of L-glycine. to γ based on fN, γ
[40] reported
based on fV should
γ = 1.35–2.02 mJ/m 2 for accurately
more represent
aqueous α-form the actual
L-glycine interfacial
solutions usingenergy of L-glycine.
the turbidity Shiau zone
metastable [40]
reported γ = 1.35–2.02 mJ/m 2 for aqueous α-form L-glycine solutions using the turbidity metastable
width measurements at the saturation temperature between 308.15 K and 328.15 K. Using the visual
zone width measurements
observation of the induction at time
the saturation
data, Devitemperature
and Srinivasan between 308.15 K γand
[25] reported mJ/m2K.for
= 5328.15 Using the
aqueous
visual observation of the induction
α-form L-glycine solutions at 303.15 K. time data, Devi and Srinivasan [25] reported γ = 5 mJ/m 2 for

aqueous α-form L-glycine solutionsA k 3 303.15 K.

Figure 7 shows the plot of J Gat versus
fV
1
T fitted to Equation (12). The fitted results are listed in
Figure 7 shows the plot of versus Afitted
A 3 to Equation (12). The fitted results are listed in
Table 4, which indicates EG = 58 kJ/mol and Jf G = 2.30 × 1026 s−4 . Although the exact value of
V
AJ AG 34,could
Table whichonlyindicates EG = 58 kJ/mol
be determined with a and
known value = 2.30
of fV×,10 s−4. Although
EG26 was the exact
not influenced value
by the of Avalue
chosen JAG3

of fV . only
could Because activation energy
be determined is usually
with a known 10–20
value of fkJ/mol
V, EG was fornot
diffusion andby
influenced 40–60 kJ/molvalue
the chosen for surface
of fV.
integration [1],
Because activation E = 58 kJ/mol obtained for the growth of L-glycine in the induction
G energy is usually 10–20 kJ/mol for diffusion and 40–60 kJ/mol for surface time experiments
should be integration
integration controlled.
[1], EG = 58 kJ/mol obtained for the growth of L-glycine in the induction time experiments
should be integration controlled.
Table 4. The fitted results of EG and AG using Equation (12).
Table 4. The fitted results of EG and AG using Equation (12).
kJ AJ AG 3 −4 AG (m/s)
EG ( mol ) fV (s 𝟑 )
AJ AG 3 (s−4 )
𝐤𝐉 𝑨𝑱 𝑨𝑮 𝟑 𝟒 293.15 K 𝑨𝑮 (𝐦/𝐬)
303.15 K 313.15 K
𝑬𝑮 ( ) (𝐬 ) 𝟒 𝑨𝑱 𝑨𝑮 (𝐬 )
58 𝐦𝐨𝐥 2.30 ×
𝒇𝑽1026 9.18 × 1022 293.15 K 104303.152.83
3.02 × K ×313.15
104 K 2.66 × 104
58 2.30 × 1026 9.18 × 1022 3.02 × 10 2.83 × 10 2.66 × 104
4 4
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A J kG 3 1
Figure 7.
Figure Theplot
7. The plotof
of fV versus
versus T fitted to
fitted to Equation
Equation (12).
(12).

Based on the study of 28 inorganic systems, Mersmann and Bartosch [41] estimated fV = 10−4−4–10−−33
Based on the study of 28 inorganic systems, Mersmann and Bartosch [41] estimated fV = 10− –10
with a detectable size of 10 µm. In the calculations here, the intermediate value, fV = 4 × 10 −44 , for
with a detectable size of 10 μm. In the calculations here, the intermediate value, fV = 4 ×
−3 . Consequently, as indicated10 , for
spherical nuclei with kV = π6 was assumed, leading to fN = 7.64 × 1011 m−3
spherical nuclei with kV = was assumed, leading to fN = 7.64 × 10 m . Consequently, as indicated
11
in Table 2, AJ was in the range 3.32 × 109 –4.91 × 109 m−3 ·s−1 based on fN = 7.64 × 1011 m−3 . Table 4
in Table 2,AAAJ was
3 in the range223.32−4 ×based
10 –4.91
9
on ×fV10= 4m×3·s
9 −
10−based
−1
4 . For on fN = 7.64 ×if10 11 m−3. Table 4 indicates
indicates J G = 9.18 × 10 s simplicity, AJ obtained based on fN
A JAG = 9.18 × 10 s based on fV = 4 × 10 . For simplicity,
was
3 22 −4 −4
adopted to find AG , one obtains AG = 2.66 × 104 –3.02 × if 10
AJ 4obtained
m/s. based on fN was adopted to
find A G, one obtains AG = 2.66 × 104–3.02 × 104 m/s.
The average growth rates and the corresponding standard deviations (SD) obtained from the
photomicroscopic growth
The average growth rates and theare
experiments corresponding
listed in Tablestandard
5. Figuredeviations
8 displays (SD) obtained
the growth ratefrom
datathe
for
photomicroscopic growth experiments are listed in Table 5. Figure 8 displays
various supersaturation from 303.15 K to 323.15 K. The growth rate obtained here is consistent with the growth rate data
for
thatvarious
reported supersaturation from
by Han et al. [23] for303.15
aqueousK toα-form
323.15L-glycine
K. The growth solutionsrateatobtained
S = 1.35 here
and T is =consistent
303.15 K.
with that reported by Han et al. [23] for aqueous α-form
Substituting Equation (11) into Equation (4) for g = 2 yields: L-glycine solutions at S = 1.35 and T = 303.15
K. Substituting Equation (11) into Equation (4) for g = 2 yields:
EG
G= 𝐺=AG𝐴exp 𝑒𝑥𝑝
(−(− )( )(𝑆S − 11) )2 ,, (13)
RT
Rearranging
Rearranging Equation
Equation (13)
(13) leads
leads to:
to:
ln[G( ) ] = ln𝐴 − E, (14)
G
ln [ 2
] = ln A G − , (14)
RT
As shown in Figure 9, a plot of ln[((S −
)
]1)versus should give a straight line, leading to EG = 57

kJ/mol
Asand AG =in6.05
shown × 109,
Figure
4 m/s.
a plot of ln [ G
] versus 1
should give a straight line, leading to EG = 57
( S −1)2 T
kJ/mol and AG = 6.05 × 104 m/s.
Crystals 2018, 8, 403 10 of 14

Table 5. The average growth rates and the corresponding standard deviations (SD) for L-Glycine.

T(K) S(−) G (SD) (×10−7 ) (m/s)

1.08 0.42 (0.17)
1.10 0.67 (0.29)
303.15
1.12 1.09 (0.36)
1.14 1.35 (0.55)
1.08 1.03 (0.42)
1.10 1.67 (0.85)
313.15
1.12 1.87 (0.64)
1.14 3.21 (1.37)
1.08 2.13 (0.73)
1.10 2.55 (0.82)
323.15
1.12 3.88 (1.03)
Crystals 2018, 8, x FOR PEER REVIEW 1.14 5.62 (2.14) 10 of 14

Figure 8. The growth rate data of L-glycine for various supersaturations at 303.15–323.15 K. The lines
Figure 8. The growth rate data of L-glycine for various supersaturations at 303.15–323.15 K. The lines
represent the fitted values to Equation (13) using g = 2, EG = 57 kJ/mol and AG = 6.05 × 104 m/s.
represent the fitted values to Equation (13) using g = 2, 𝐸 = 57 kJ/mol and 𝐴 = 6.05 × 10 m/s.

Figure 8 shows the growth rate data fitted well to Equation (14) using g = 2 and the fitted values
Table 5. The average growth rates and the corresponding standard deviations (SD) for L-Glycine.
of EG and AG . Thus, it was reasonable to adopt the power-law growth rate of Equation (4) with g = 2 in
derivation of𝑻(𝐊) 𝑺(−)
Equation (10). It should be noted that the 𝑮 (𝑺𝑫) (×
turbidity 𝟏𝟎 𝟕 ) (𝐦/𝐬)
induction time data were measured
1.08µm, as assumed here for fV = 40.42
for nuclei of near-zero size (<10 −4 and f = 7.64 × 1011 m−3 ) in
(0.17)
× 10 N
1.10 the photomicroscopic growth0.67
the 200 mL stirred solution while data(0.29)
were measured for nuclei of size
303.15
1.12
L = 50–100 µm in the 20 mL stagnant solution. Nevertheless, E1.09 (0.36) from the growth rate data
G obtained
was close to that obtained from1.14the induction time data while A1.35 (0.55) from the growth rate data
G obtained
was still quite consistent with1.08
that obtained from the induction1.03
time(0.42)
data.
1.10 1.67 (0.85)
313.15
1.12 1.87 (0.64)
1.14 3.21 (1.37)
1.08 2.13 (0.73)
1.10 2.55 (0.82)
323.15
1.12 3.88 (1.03)
1.14 5.62 (2.14)

Figure 8 shows the growth rate data fitted well to Equation (14) using g = 2 and the fitted values
Crystals 2018,8,8,403
Crystals2018, x FOR PEER REVIEW 11
11ofof14
14

Figure9.9.The
Figure Thegrowth
growthrate
ratedata
dataofofL-glycine
L-glycinefor
forvarious
varioussupersaturations
supersaturationsatat303.15–323.15
303.15–323.15KKfitted
fittedtoto
Equation
Equation(14).
(14).
5. Conclusions
5. Conclusions
In practical applications, the turbidity induction time measurements should be more related to the
In practical applications, the turbidity induction time measurements should be more related to
volume fraction of the nuclei than to the number density of the nuclei. A model is developed in this
the volume fraction of the nuclei than to the number density of the nuclei. A model is developed in
work to determine the interfacial energy and growth activation energy of aqueous L-glycine solutions
this work to determine the interfacial energy and growth activation energy of aqueous L-glycine
from the turbidity induction time data without the knowledge of the actual growth kinetics. The
solutions from the turbidity induction time data without the knowledge of the actual growth kinetics.
results reveal that the interfacial energy of L-glycine obtained in this work is close to that calculated
The results reveal that the interfacial energy−of L-glycine obtained in this work is close to that
based on the traditional method by assuming ti 1 ∝ J, and the growth activation energy of L-glycine
calculated based on the traditional method by assuming 𝑡 ∝ 𝐽, and the growth activation energy
obtained from the induction time data was close to that obtained from the photomicroscopic growth
of L-glycine obtained from the induction time data was close to that obtained from the
experiments. The kinetic growth parameter of L-glycine obtained from the photomicroscopic growth
photomicroscopic growth experiments. The kinetic growth parameter of L-glycine obtained from the
experiments was consistent with that obtained from the induction time data. Thus, the proposed
photomicroscopic growth experiments was consistent with that obtained from the induction time
model in this work provides an efficient method to determine the nucleation and growth kinetics of
data. Thus, the proposed model in this work provides an efficient method to determine the nucleation
nuclei using the induction time data.
and growth kinetics of nuclei using the induction time data.
Funding: The author would like to thank Chang Gung Memorial Hospital (CMRPD2G0241) and Ministry of
Science andThe
Funding: Technology of Taiwan
author would like (MOST106-2221-E-182-053) for financial
to thank Chang Gung Memorial support
Hospital of this research.
(CMRPD2G0241) and Ministry of
Science and Technology of Taiwan (MOST106-2221-E-182-053) for financial support of this research.
Acknowledgments: The author would like to thank Chang Gung Memorial Hospital (CMRPD2G0241) and
Ministry of Science and
Acknowledgments: TheTechnology of Taiwan
author would (MOST106-2221-E-182-053)
like to thank Chang Gung Memorial for financial support
Hospital of this research.
(CMRPD2G0241) and
The author also expresses his gratitude to Szu-Yu Lin and Yi-Ting Chen for their experimental work.
Ministry of Science and Technology of Taiwan (MOST106-2221-E-182-053) for financial support of this research.
Conflicts
The authorof also
Interest: The author
expresses declares
his gratitude to no conflict
Szu-Yu Linof interest.
and Yi-TingThe
Chenfunders hadexperimental
for their no role in the design of the
work.
study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to
publish theof
Conflicts results.
Interest: The author declares no conflict of interest. The funders had no role in the design of the
study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision
to publish the results.

Notation
𝐴 growth kinetic parameter (m/s)
𝐴 nucleation kinetic parameter (m s )
𝐶 concentration of solutes (kg solute/kg solution )
𝐶 saturated concentration of solutes (kg solute/kg solution )
𝐸 growth activation energy (J/mol )
Crystals 2018, 8, 403 12 of 14

Notation
AG growth kinetic parameter (m/s)
nucleation kinetic parameter m−3 s−1


AJ
C concentration of solutes (kg solute/kg solution)
saturated concentration of solutes
Ceq
(kg solute/kg solution)
EG growth activation energy (J/mol)
minimum detectable number density of nuclei for a
fN
detector m−3

minimum detectable volume density of nuclei for a

fV
detector (−)
G growth rate (m/s)
g growth rate order (−)
nucleation rate m−3s−1


J 
kB Boltzmann constant = 1.38 × 10−23 JK−1
kG growth rate constant (m/s)
kV volume shape factor (−)
L size of a nucleus
 (m) 
MW molar mass kg mol−1
 
NA Avogadro number = 6.02 × 1023 mol−1
J
R ideal gas constant (= 8.314 mol−K )
S supersaturation ratio (−)
T temperature (K)
t time (s)
ti induction time (s)
V volume of a nucleus (m3 )

Greek letters
2


γ interfacial energy
 J/m 
ρC crystal density kg m−3
v volume of the solute molecule (m3 )

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