Ultrasonics Sonochemistry xxx (2014) xxx–xxx

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Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultson

Ultrasound assisted nucleation and growth characteristics of glycine

polymorphs – A combined experimental and analytical approach
K. Renuka Devi, A. Raja, K. Srinivasan ⇑
Crystal Growth Laboratory, Department of Physics, Bharathiar University, Coimbatore 641046, Tamil Nadu, India

a r t i c l e i n f o a b s t r a c t

Article history: For the first time, the effect of ultrasound in the diagnostic frequency range of 1–10 MHz on the
Received 26 July 2014 nucleation and growth characteristics of glycine has been explored. The investigation employing
Received in revised form 18 October 2014 the ultrasonic interferometer was carried out at a constant insonation time over a wide range of relative
Accepted 5 November 2014
supersaturation from r = 0.09 to 0.76 in the solution. Ultrasound promotes only a nucleation and
Available online xxxx
completely inhibits both the b and c nucleation in the system. The propagation of ultrasound assisted
mass transport facilitates nucleation even at very low supersaturation levels in the solution. The presence
Keywords:
of ultrasound exhibits a profound effect on nucleation and growth characteristics in terms of decrease in
Nucleation
Optical microscopy
induction period, increase in nucleation rate and decrease in crystal size than its absence in the solution.
X-ray diffraction With an increase in the frequency of ultrasound, a further decrease in induction period, increase in
Growth from solutions nucleation rate and decrease in the size of the crystal is noticed even at the same relative supersaturation
levels. The increase in the nucleation rate explains the combined dominating effects of both the
ultrasound frequency and the supersaturation in the solution. Analytically, the nucleation parameters
of the nucleated polymorph have been deduced at different ultrasonic frequencies based on the classical
nucleation theory and correlations with the experimental results have been obtained. Structural
affirmation of the nucleated polymorph has been ascertained by powder X-ray diffraction.
Ó 2014 Elsevier B.V. All rights reserved.

1. Introduction
Crystallization, a phase change occurring in solution is the main
key technique employed in the separation, purification and pro-
duction of a wide range of materials. Over the past decades crystal-
lization has been augmented by a lot of methods, techniques and
recently ultrasound have evolved as a powerful tool in inducing
and investigating this crystallization mechanism in various sys-
tems. Though ultrasound has been reported to influence every
aspect of the crystallization process its effect on the phenomenon
of nucleation is highly significant. In addition to the initiation of
nucleation in the system, irradiation of ultrasound was also found
to influence several other factors of crystallization such as poly-
morphism, agglomeration, crystal size etc. [1–15]. Ultrasound has
proven as an efficient tool to establish control over the number
of primary nuclei and their crystal size. Li et al. [5] has studied
the relation between the insonation periods and the size of the
resulted crystals. Nanev and Penkova stated that narrow size dis-
tribution could be achieved in the presence of ultrasound, but still
⇑ Corresponding author. Tel.: +91 422 2428442; fax: +91 422 2422387.
E-mail address: nivas_5@yahoo.com (K. Srinivasan).
the end results are characteristic of the target material used [16].
Lyczko et al. studied the cooling-based primary nucleation in the
presence of ultrasound and revealed the effect of ultrasound on
the reduction of the metastable zone width and induction time
and thereby the solid formation rate [17]. Guo et al. studied the
anti-solvent crystallization process in the presence of ultrasound
and obtained the same reduced effect on the metastable zone
width and induction time as obtained by Lyczko et al. [18].
Miyasaka et al. revealed that there was an energy threshold above
which ultrasonic irradiation increased the crystal number and
promoted nucleation, at the region where a low level of ultrasonic
energy was applied [19]. Moreover, sonocrystallization studies on
amino acids by Kurotani et al., again pointed out that the induction
time increased with increasing ultrasonic irradiation energy up to a
certain degree and then decreased, indicating the earlier energy
threshold theory [20]. In most applications, ultrasonic frequency
in the range of kilohertz is utilized while, the use of megahertz
range ultrasound is rarely reported [21,22]. The use of higher
frequency ultrasound avoids the problem of cavitation erosion
and in the megahertz frequency range, a different environment
for crystallization will be created due to higher acceleration of
medium as well as formation of smaller bubbles than 20 kHz

http://dx.doi.org/10.1016/j.ultsonch.2014.11.006
1350-4177/Ó 2014 Elsevier B.V. All rights reserved.

Please cite this article in press as: K. Renuka Devi et al., Ultrasound assisted nucleation and growth characteristics of glycine polymorphs – A combined
experimental and analytical approach, Ultrason. Sonochem. (2014), http://dx.doi.org/10.1016/j.ultsonch.2014.11.006
2 K. Renuka Devi et al. / Ultrasonics Sonochemistry xxx (2014) xxx–xxx

[22]. Although cavitation effects become comparatively gentler 3. Results and discussion
than 20 kHz, a high frequency ultrasound increases the number
density of bubbles and potentially enhances bubble-related 3.1. Effect of ultrasound on the induction period of nucleation
phenomena such as interfacial adsorption, bubble interaction,
bubble oscillation, microstreaming etc. [23,24]. Glycine the When the solutions saturated in the temperature range from 30
simplest amino acid and a very interesting molecule exhibiting to 70 °C were cooled down to 32 °C a relative supersaturation is
the phenomenon of polymorphism with three polymorphs a, b generated in the range from r = 0.09 to 0.76 in the solution. In
and c under ambient conditions is the target material in the our experiment, the induction periods of nucleation were mea-
present work [25–31]. From the existing literature it is clear that, sured both in the presence (insonated) and absence (uninsonated)
so far the effects of ultrasonic frequencies only up to 1.6 MHz have of ultrasound and compared quantitatively under various super-
been experimented on glycine crystallization while the effects of saturations. The measured induction period of nucleation both in
frequencies beyond this is unrevealed. Hence this form the novel the absence and presence of ultrasound over the entire supersatu-
objective of this work that is to reveal for the first time the effects ration range is shown in Fig. 2a and b, respectively.
of ultrasound in the diagnostic frequency range of 1–10 MHz on No nucleation was observed in the lower supersaturation range
the nucleation and growth characteristics of glycine polymorphs. from r = 0.09 to 0.07 in the solution in the absence of ultrasound
The experiments were also carried out at a constant insonation as shown in Fig. 2a. While only above the supersaturation of
time over a wide range of relative supersaturation from r = 0.15 nucleation was observed in the solution. At the supersat-
r = 0.09 to 0.76 in the solution in order to study the dominating uration of r = 0.15, the induction period of nucleation was higher
and overlapping effects of ultrasound and supersaturation in of about 28 min and with further increase in supersaturation from
assisting the nucleation in the solution. r = 0.15 to 0.76, the induction period of nucleation decreases from
28 to 2 min in the solution.
In the presence of ultrasound even at the lower frequency of
2. Materials and methods 1 MHz, nucleation has been induced in the lower supersaturation
range from r = 0.09 to 0.07 in the solution as evident from
Glycine (G.R. Grade, Merck) and laboratory double distilled Fig. 2b. Ultrasound with its inherent phenomenon of mixing and
water were used for solution preparation. Solutions of glycine each cavitation due to its propagation in the solution medium promotes
of about 100 mL capacity were saturated at different temperatures the mass transfer and thereby the nucleation in the solution [5]. In
in the range from 30 to 70 °C in steps of 5 °C in a 250 mL round
bottom flask fitted with ground sleeve attachment for effective
stirring. The solution was saturated for about 12 h at a stirring
speed of 150 rpm. The entire set up was placed inside a CTB having
the temperature controlling accuracy of about ±0.01 °C. After
saturation, the solution was filtered using Whatman No. 41 filter
sheets into another similar RBF and maintained at the saturation
temperature for 1 h. The entire solution was split up into capacities
of 5 mL each into 20 test tubes. The temperature of the CTB was
then reduced to 32 °C and maintained in it for 1 h. The solutions
were then transferred into ultrasonic irradiation chambers and
set for irradiation. One set of solution was kept apart to study
the effects in the absence of ultrasound. A multi-frequency ultra-
sonic interferometer shown in Fig. 1 was used for the experiments.
A constant insonation time of 5 min was employed in all the cases.
After insonation, about 500 lL of the insonated solution was
pipetted out onto a microscope slide for investigation under the
optical microscope and the nucleation events were recorded. The
type of polymorph nucleated was ascertained based on their
morphology and confirmed further by powder X-ray diffraction
through BRUKER D8 Advance powder X-ray diffractometer.

Fig. 2. Variations in the induction period of nucleation in (a) absence and (b)
Fig. 1. Experimental setup. presence of ultrasound in the solution.

Please cite this article in press as: K. Renuka Devi et al., Ultrasound assisted nucleation and growth characteristics of glycine polymorphs – A combined
experimental and analytical approach, Ultrason. Sonochem. (2014), http://dx.doi.org/10.1016/j.ultsonch.2014.11.006
 K. Renuka Devi et al. / Ultrasonics Sonochemistry xxx (2014) xxx–xxx
Fig. 3. Reduction in the induction period of nucleation during insonation at
r = 0.34.
the presence of ultrasound, the induction periods of nucleation are
obviously shorter than those in their absence at the same supersat-
uration. Moreover the increase in ultrasonic frequencies from 1 to
10 MHz reduces the induction period of nucleation further. At the
same relative supersaturation of r = 0.34, the induction period in
the uninsonated solution is 14 min and in the case of insonated
solutions over the entire frequency range from 1 to 10 MHz, the
induction periods of nucleation decreased tremendously as shown
in Fig. 3. From the above results it is clear that, insonation pro-
motes nucleation and the acceleration in the diffusion of the solute
molecules might be the reason behind this reduction in the induc-
tion period of nucleation [5].
3.2. Effect of ultrasound on the nucleation behaviour of glycine
polymorph
In the absence of ultrasound, no nucleation was observed in the
lower supersaturation range from r = 0.09 to 0.07 while, 100% a
polymorph with its characteristic bipyramidal morphology was
observed over the rest of the supersaturation range from r = 0.15
to 0.76 in the solution as shown in Fig. 4a.
In the case of insonated solution, over the entire range of super-
saturation from r = 0.09 to 0.76 and ultrasonic frequencies from
1 to 10 MHz only 100% a nucleation was observed. Neither the
nucleation of b nor c was induced in the solution in the presence
of ultrasound over a wide range of frequencies as evident from
the nucleation matrix of the experimental outcomes shown in
Fig. 4b. The microscopic images depicting the nucleation behaviour
of glycine polymorphs at different supersaturation levels and ultra-
sonic frequencies are shown in Fig. 4c. From the figure it could be
clearly visualized that, only a form has nucleated at all the super-
saturation and ultrasonic frequencies and these results quantify
the inefficiency of ultrasound in influencing the polymorphism of
σ = 0.15 Uninsonated
10 μm
Fig. 4a. Microscopic images of a polymorph nucleated in the uninsonated solution.
Please cite this article in press as: K. Renuka Devi et al., Ultrasound assisted nucleation and growth characteristics of glycine polymorphs – A combined
experimental and analytical approach, Ultrason. Sonochem. (2014), http://dx.doi.org/10.1016/j.ultsonch.2014.11.006
3
Fig. 4b. Nucleation matrix of the experimental outcomes, both in the insonated and
uninsonated solutions.
glycine and promoting the nucleation of other polymorphs in the
solution. Generally a nucleation occurs with dimers as the basic
building units, while the c and b occurs only with monomers as
basic blocks. In solution due to the existence of glycine as zwitter-
ions only dimers are spontaneously formed due to self-charge
compensation and the probability of the glycine zwitterions to sus-
tain as monomers remain very low. Hence, only a nucleation is
spontaneously observed rather than the c or b nucleation in pure
glycine aqueous solution. This nucleation of c or b is generally
obtained only by induced charge compensation that enables the
monomeric retainment of glycine molecules [32]. From the
obtained results it is clear that the propagation of ultrasound in
no way influences the retainment of molecules as monomers and
hence only a nucleation is observed due to dimer formation.
In addition to the above visual confirmation, the nucleated
polymorph was also confirmed further by subjecting them to
PXRD. The powder X-ray diffraction patterns recorded for the crys-
tals nucleated both in the uninsonated and in the insonated solu-
tions are shown in Fig. 5. From the recorded patterns it is clear
that the crystals nucleated both in the uninsonated and in the
insonated solutions are a form of glycine with their characteristic
2h peak at 29.85° 2h [32]. Moreover, the patterns of the crystals
nucleated at r = 0.15 with 1, 5 and 10 MHz makes clear that inson-
ation process has no influence over the polymorphism of glycine.
3.3. Effect of ultrasound on the nucleation rate of glycine polymorph
Insonation exhibits a positive effect on the nucleation by induc-
ing it even at much lower supersaturation levels in the solution.
The number of nucleations observed per unit area per unit time
in the absence of ultrasound is less than that observed in its pres-
ence in the solution. The number of nucleations observed in the
case of insonated solutions at different supersaturation and at dif-
ferent ultrasonic frequencies is shown in Fig. 6. This figure clearly
explains the dominating effects of both the supersaturation and
the ultrasonic frequencies in the solution. At the frequency of
1 MHz, the number nucleation increases with the increase in rela-
tive supersaturation in the solution. Though the increase in the
number of nucleation with the increase in supersaturation is a
well-known effect this has been promoted further by the presence
of ultrasound. The presence of ultrasound enhances the number of
nucleations observed for the same supersaturation also. The drastic
enhancement in the number of nucleations with the increase in
ultrasonic frequencies from 1 to 10 MHz could be more clearly
visualized from the microscopic images shown in Fig. 4c.
4 K. Renuka Devi et al. / Ultrasonics Sonochemistry xxx (2014) xxx–xxx

Fig. 4c. Microscopic images of a polymorph nucleated at different supersaturation levels and ultrasonic frequencies.

Fig. 6. Increase in the nucleation rate with ultrasonic frequencies.

Fig. 5. Powder X-ray diffraction pattern of the crystals nucleated in the uninson-
ated and in the insonated solutions.
The reason behind the increase in the nucleation rate with
increasing ultrasonic frequencies may be due to the postulates
which states that during the propagation of ultrasound in the
supersaturated solution in cycles of compression and rarefaction
it induces transient cavitation which in turn facilitates the
formation of gas/vapour cavities [33,34]. The observation of
cavitation in the frequency ranges of up to 10 MHz in the solution
has been clearly evidenced by several researchers [35–41]. Hence,
during the rarefaction these gas/vapour cavities collapse, creating
high temperature and pressure that initially decreases the
supersaturation and increases the metastable zone width in the
solution. But as a result of solvent evaporation due to rise in tem-
perature the solution gets highly supersaturated instantly, thereby
reducing the metastable zone width and promoting the nucleation
in the solution [33,42]. Moreover, it is also stated that, the vapou-
rization of solvent in the vicinity of cavity causes the solution to
undergo rapid local cooling, which in turn creates the necessary
supersaturation for nucleation in the solution [12,43,44]. In addi-
tion, the enhancement in the nucleation rate with the increase in
ultrasonic frequency might also be a promoted effect of ultrasound
on secondary nucleation by increasing the mass transport of solute
molecules in the solution [45,46].

Please cite this article in press as: K. Renuka Devi et al., Ultrasound assisted nucleation and growth characteristics of glycine polymorphs – A combined
experimental and analytical approach, Ultrason. Sonochem. (2014), http://dx.doi.org/10.1016/j.ultsonch.2014.11.006
 K. Renuka Devi et al. / Ultrasonics Sonochemistry xxx (2014) xxx–xxx 5

equilibrium concentration, V is the atomic volume, and S is the rel-

ative supersaturation defined by (C  Co)/Co. The critical size of a
stable spherical nucleus r⁄, and the critical energy barrier that a
nucleation process must overcome DG⁄, are defined by,

r ¼ 2c=DGv ð3Þ

DG ¼ 16pc3 =3ðDGv Þ2 ð4Þ

The number of growth molecules in a critical nucleus is defined
by [48,49]:

i ¼ ½4pðr  Þ3 =3V

ð5Þ
The rate of nucleation J per unit volume is given by,

J ¼ J o expðDG =kTÞ ð6Þ

3 2
J ¼ J o exp½ð16pc3 V 2 Þ=ð3k T 3 ðln SÞ Þ ð7Þ
Fig. 7. Decrease in the crystallite size with ultrasonic frequencies.
Jo is the pre-exponential factor and is given by,
3.4. Effect of ultrasound on the growth rate of glycine polymorph 5 
J o ¼ ½ðD=dm i Þð4DG =3pkTÞ
1=2
 ð8Þ

The size of the crystal gets reduced with the increase in relative where dm is the molecular diameter and D is the diffusion coeffi-
supersaturation in solutions either in the absence or presence of cient of the solute.
ultrasound. In the absence of ultrasound, the size of the crystal dm and D are calculated using the equations:
reduces from 42 to 22 lm in relative supersaturation from
r = 0.15 to 0.76 in the solution. While in the presence of 1 MHz dm ¼ ½1=ðC c NÞ1=3 ð9Þ
of ultrasound, the size of the crystal reduces from 27.5 to 20 lm
in relative supersaturation from r = 0.15 to 0.76 in the solution. D ¼ ½ðkTÞ=ð3pldm Þ ð10Þ
This reduction might be a direct consequence of the increase in
the nucleation rate at high supersaturation. But apart from this where Cc is the molar density of the solute, N is the Avogadro num-
effect, ultrasound also plays a dominant role in the interplay of ber and l the dynamic viscosity of the solution. Based on the above
the reduction in crystal size. formalism, the nucleation parameters were estimated for the nucle-
The size of the crystal obtained in the presence of ultrasound is ations obtained in solutions both in the absence of ultrasound and
smaller than that obtained in the absence of ultrasound in the solu- in the presence of ultrasonic frequencies in the range from 1 to
tion. At r = 0.15, the size of the crystal obtained in the presence of 10 MHz over the entire supersaturation range for comparison. The
ultrasound at the frequency of 1 MHz is 27.5 lm and it is much estimated nucleation parameters such as interfacial energy (c), crit-
reduced from the crystal size of 42 lm obtained in the absence ical radius (r⁄), activation energy barrier (DG⁄), critical number of
of ultrasound. Moreover, with further increase in the frequency molecules (i⁄) and nucleation rate (J) for the uninsonated solution
of ultrasound from 1 to 10 MHz the crystal size gets reduced fur- and that for solutions insonated with 1, 5 and 10 MHz are presented
ther for same supersaturation. At the same r = 0.15, with the in Tables 1–5, respectively.
increase in frequency to 10 MHz, the size of the crystal gets
reduced to 5 lm (i.e.) narrow size distribution is achieved. Inson- Table 1
ation leads to crystals with reduced size than that obtained by con- Interfacial energy both in the uninsonated and in the insonated solutions.
ventional processes while the morphology of the obtained crystals
Interfacial energy c (mJ/m2)
remains unaltered. The reduction in crystal size noticed with the
increase in supersaturation and ultrasonic frequencies in the solu- r Absence 1 MHz 5 MHz 10 MHz

tion is shown in Fig. 7. 0.15 0.21 0.24 0.26 0.27

0.25 0.39 0.42 0.43 0.44
0.34 0.58 0.57 0.59 0.60
3.5. Estimation of nucleation parameters 0.46 0.77 0.75 0.78 0.80
0.57 0.85 0.89 0.95 0.97
Analytically the nucleation parameters were estimated based 0.66 1.01 0.99 1.07 1.12
on the Classical Nucleation Theory using the experimentally deter- 0.76 1.11 1.01 1.14 1.26

mined induction periods. These induction periods were plotted

according to the below equation at constant T and the interfacial
energies c were estimated [47]. Table 2
2 3 Critical radius both in the uninsonated and in the insonated solutions.
ln s 1 ½B=ðln SÞ  where B ¼ ½16pc3 V 2 =3k T 3  ð1Þ
Critical radius r⁄ (1010 m)
The driving force for both nucleation and growth is the reduc-
r Absence 1 MHz 5 MHz 10 MHz
tion in Gibbs free energy and the change of Gibbs free energy per
0.15 0.75 0.67 0.66 0.64
unit volume depends on the concentration of the solute as shown
0.25 0.74 0.66 0.65 0.63
by the equation: 0.34 0.73 0.65 0.64 0.61
0.46 0.70 0.64 0.63 0.60
DGv ¼ ½kT lnðC=C o Þ=V ¼ ½kT lnð1 þ SÞ=V ð2Þ 0.57 0.68 0.63 0.61 0.58
0.66 0.67 0.62 0.60 0.55
where k is the Boltzmann’s constant, T is the temperature of the
0.76 0.64 0.61 0.56 0.49
solution in K, C is the actual concentration of the solute, Co is the

Please cite this article in press as: K. Renuka Devi et al., Ultrasound assisted nucleation and growth characteristics of glycine polymorphs – A combined
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6 K. Renuka Devi et al. / Ultrasonics Sonochemistry xxx (2014) xxx–xxx

Table 1 reveals that with the increase in supersaturation, the Table 5

interfacial energy increases for both the uninsonated and insonat- Nucleation rate both in the uninsonated and in the insonated solutions.

ed solutions from 0.21 to 1.11 mJ/m2 and from 0.26 to 1.26 mJ/m2, Nucleation rate J (1024 m2 S4)
respectively thereby indicating the formation of a solid phase in r Absence 1 MHz 5 MHz 10 MHz
the solution medium. Moreover, for the same supersaturation also,
0.15 107.25 129.60 134.73 138.06
the interfacial energy increases with the increase in ultrasonic fre- 0.25 140.84 168.32 175.64 180.61
quency. At r = 0.15, the interfacial energy increases from 0.24 to 0.34 171.37 203.03 210.04 221.11
0.27 mJ/m2 with the increase in the ultrasonic frequency from 1 0.46 207.77 238.97 248.09 263.38
to 10 MHz. 0.57 242.43 272.69 283.76 312.94
0.66 267.85 300.74 321.71 359.97
From the Tables 2–4 it could be observed that, with the increase
0.76 309.74 328.12 379.80 458.79
in supersaturation, the critical radius, activation energy barrier and
the critical number molecules decreases for both the uninsonated
and insonated solutions. The critical radius decreases from 0.75 increasing the nucleation rate and thereby decreasing the crystal
to 0.64  1010 m in the case of uninsonated solution and size leading to narrow size distribution.
decreases from 0.67 to 0.49  1010 m in the case of insonated
solution. The activation energy barrier and the critical number of 4. Conclusions
molecules decrease from 22.80 to 7.27  1024 J/m3 and from
23.14 to 13.93, respectively in the case of uninsonated solution. The ultrasonic irradiation employed in the present work proved
While the activation energy barrier and the critical number of mol- as a successful tool in inducing the nucleation of glycine even at
ecules decreases from 19.74 to 4.40  1024 J/m3 and from 15.87 to lower supersaturation levels. Ultrasound employed over the entire
6.38, respectively in the case of insonated solutions. Moreover, the frequency range from 1 to 10 MHz facilitates only a nucleation in
increase in ultrasonic frequencies at constant supersaturation also the system and no nucleation of either c or b was observed in
shows a tremendous decrease in the interfacial energy, activation the solution. This result reveals the inefficiency of ultrasound to
energy barrier and in the critical number of molecules. enable the glycine molecules to sustain as monomers and to influ-
At r = 0.15, r⁄ decreases from 0.67 to 0.64  1010 m, DG⁄ ence the polymorphism of glycine in the solution. Ultrasound
decreases from 19.74 to 12.68 J/m3 and i⁄ decreases from 15.87 reduces the induction period of nucleation than that in the absence
to 13.99 with an increase in the ultrasonic frequencies from 1 to of ultrasound in the solution. The induction periods of nucleation
10 MHz. These results show that the insonation reduces the barrier gradually reduces with increase in the ultrasonic frequencies even
that inherently exist for nucleation and promotes the nucleation at the same supersaturation. Nucleation rate increases with the
even at lower supersaturation levels and at lower induction increase in supersaturation in both the uninsonated and insonated
periods. solutions. Moreover, in the presence of ultrasound over the wide
Table 5 reveals the increase in the nucleation rate both in the range of frequencies the nucleation rate increases further than that
uninsonated and in the insonated solutions from 107.25 to in uninsonated solution. The combined effects of supersaturation
309.74  1024 m2 S4 and from 129.60 to 458.79  1024 m2 S4 and ultrasonic frequencies play a dominating role in influencing
respectively with the increase in supersaturation. Moreover, even the nucleation rate of a polymorph and this in turn has a direct
at constant supersaturation, the increase in the ultrasonic fre- influence over the size of the nucleated crystal. The size of the crys-
quency increases the nucleation rate. At a constant supersaturation tal gets drastically reduced in the presence of ultrasound over the
of r = 0.15, the nucleation rate increases from 129.60 to wide range of frequencies than that in uninsonated solution and
138.06  1024 m2 S4 as the ultrasonic frequency increases from this enables the achievement of narrow crystal size distribution
1 to 10 MHz. These results quantify the effect of ultrasound in in the system. The analytically deduced nucleation parameters
expose more evidently the experimentally obtained results and
reveal clearly the influence of ultrasound on glycine crystallization
Table 3 and polymorphism.
Activation energy barrier both in the uninsonated and in the insonated solutions.

Activation energy barrier DG⁄ (1024 J/m3) Acknowledgements

r Absence 1 MHz 5 MHz 10 MHz
One of the authors (K.S.) gratefully acknowledges the
0.15 22.80 19.74 15.86 12.68
0.25 22.13 18.12 14.99 12.34 Department of Science and Technology, Government of India, for
0.34 20.48 16.22 14.77 11.26 providing financial support for this work through Science and
0.46 18.04 13.67 12.69 10.15 Engineering Research Board (DST-SERB) and for providing funds
0.57 14.94 10.67 9.97 9.00 to establish the powder XRD facility in the Department of Physics
0.66 11.32 7.94 7.30 6.90
0.76 7.27 4.99 4.62 4.40
through its ‘‘Fund for Improvement of S&T infrastructure
(DST-FIST)’’ programme. The other author (K.R.) gratefully
acknowledges the Council of Scientific and Industrial Research
(CSIR), Government of India, for providing the Senior Research
Table 4 Fellowship (CSIR-SRF).
Critical number of molecules both in the uninsonated and in the insonated solutions.

Critical number of molecules i⁄ References

r Absence 1 MHz 5 MHz 10 MHz
[1] Y.H. Kim, K. Lee, K.K. Koo, Y.G. Shul, S. Haam, Cryst. Res. Technol. 37 (2002)
0.15 23.14 15.87 14.68 13.99 928.
0.25 21.96 15.40 14.15 13.39 [2] C.J. Price, Pharm. Technol. Eur. 12 (1997) 59.
0.34 20.72 14.79 13.82 12.48 [3] D.R. Kelly, S.J. Harrison, S. Jones, M.A. Masood, J.J.G. Morgan, Tetrahedron Lett.
0.46 18.76 14.21 13.19 11.72 34 (1993) 2689–2690.
0.57 17.12 13.56 12.53 10.32 [4] N. Lyczko, F. Espitalier, J. Schwartzentruber, Fourteenth International Symposium
0.66 16.35 12.99 11.37 9.09 on Industrial Crystallization, Warwickshire, UK, 1999, pp. 1658–1669.
0.76 13.93 12.43 9.30 6.38 [5] H. Li, J. Wang, Y. Bao, Z. Guo, M. Zhang, J. Cryst. Growth 247 (2003) 192–198.
[6] K.S. Suslick, Sonochem. Sci. 247 (1990) 1439–1445.

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experimental and analytical approach, Ultrason. Sonochem. (2014), http://dx.doi.org/10.1016/j.ultsonch.2014.11.006
 K. Renuka Devi et al. / Ultrasonics Sonochemistry xxx (2014) xxx–xxx
[7] N. Amara, B. Ratsimba, A. Wilhelm, H. Delmas, Ultrason. Sonochem. 8 (2001)
S265–S270.
[8] L.C. Hagenson, L.K. Doraiswamy, Chem. Eng. Sci. 53 (1998) 131–148.
[9] C.J. Price, Chem. Eng. Prog. 93 (1997) 34–43.
[10] L.H. Tompson, L.K. Doraiswamy, Chem. Eng. Sci. 55 (2000) 3085–3090.
[11] N. Amara, B. Ratsimba, A. Wilhelm, H. Delmas, Ultrason. Sonochem. 11 (2004)
17–21.
[12] S. Gracin, M. Uusi-Penttila, A.C. Rasmuson, Cryst. Growth Des. 5 (2005) 1787–
1794.
[13] E. Miyasaka, M. Takai, H. Hidaka, Y. Kakimoto, I. Hirasawa, Ultrason.
Sonochem. 13 (4) (2005) 308–312.
[14] H.W. Anderson, et al., US Patent 5.471.001, 28 November 1995.
[15] S. Kim, C. Wei, S. Kiang, Org. Process Res. Dev. 7 (2003) 997–1001.
[16] C.N. Nanev, A. Penkova, J. Cryst. Growth 232 (2001) 285–293.
[17] N. Lyczko, F. Espitalier, O. Louisnard, J. Schwartzentruber, Chem. Eng. J. 86
(2002) 233–241.
[18] Z. Guo, M. Zhang, H. Li, J. Wang, E. Kougoulos, J. Cryst. Growth 273 (2005) 555–
563.
[19] E. Miyasaka, Y. Kato, M. Hagisawa, I. Hirasawa, J. Cryst. Growth 289 (2006)
324–330.
[20] M. Kurotani, E. Miyasaka, S. Ebihara, I. Hirasawa, J. Cryst. Growth 311 (2009)
2714–2721.
[21] T. Ichitsubo, E. Matsubara, S. Kai, M. Hirao, Acta Mater. 52 (2004) 423–429.
[22] Susumu Nii, Saki Takayanagi, Ultrason. Sonochem. 21 (2014) 1182–1186.
[23] M. Ashok Kumar, J. Lee, S. Kentish, F. Grieser, Ultrason. Sonochem. 14 (2007)
470–475.
[24] T.G. Leighton, The Acoustic Bubble, Academic Press, San Diego, 1994.
[25] R.E. Marsh, Acta Crystallogr. 11 (1958) 654–663.
[26] Y. Iitaka, Acta Crystallogr. 13 (1960) 35–45.
[27] Y. Iitaka, Acta Crystallogr. 14 (1961) 1–10.
[28] K. Allen, R.J. Davey, E. Ferrari, C. Towler, G.J. Tiddy, M.O. Jones, R.G. Pritchard,
Cryst. Growth Des. 2 (2002) 523–527.
Please cite this article in press as: K. Renuka Devi et al., Ultrasound assisted nucleation and growth characteristics of glycine polymorphs – A combined
experimental and analytical approach, Ultrason. Sonochem. (2014), http://dx.doi.org/10.1016/j.ultsonch.2014.11.006
7
[29] I. Weissbuch, L. Leiserowitz, M. Lahav, Adv. Mater. 6 (1994) 952–956.
[30] E.V. Boldyreva, V.A. Drebushchak, T.N. Drebushchak, I.E. Paukov, Y.A.
Kovalevskaya, E.S. Shutova, J. Therm. Anal. Calorim. 73 (2003) 409–418.
[31] E.A. Losev, M.A. Mikhailenko, A.F. Achkasov, E.V. Boldyreva, New J. Chem. 37
(7) (2013) 1973–1981.
[32] K. Renuka Devi, K. Srinivasan, J. Cryst. Growth 364 (2013) 88–94.
[33] V.S. Sutkar, P.R. Gogate, Chem. Eng. J. 155 (2009) 26–36.
[34] D. Chen, Applications of ultrasound in water and wastewater treatment, in: D.
Chen, S.K. Sharma, A. Mudhoo (Eds.), Handbook on Applications of
Ultrasound: Sonochemistry for Sustainability, Press/Taylor & Francis Group,
2011.
[35] Dietmar Peters, J. Mater. Chem. 6 (10) (1996) 1605–1618.
[36] Kenneth S. Suslick, Science 247 (1990) 1439–1445.
[37] F.A. Duck, A.C. Baker, H.C. Starritt, Ultrasound in Medicine, IOP Publishing
Limited, London, 1998.
[38] Y.T. Shah, A.B. Pandit, V.S. Mohalkar, Cavitation Reaction Engineering, Springer,
US, 1999 (Kluwer Academic/Plenum Publishers, New York).
[39] Martin Wiklund, Lab Chip 12 (2012) 2018–2028.
[40] Jin Ho Bang, Kenneth S. Suslick, Adv. Mater. 22 (2010) 1039–1059.
[41] Nancy N. Byl, Phys. Ther. 75 (1995) 539–553.
[42] Graham Ruecroft, David Hipkiss, Tuan Ly, Neil Maxted, Peter W. Cains, Org.
Process Res. Dev. 9 (2005) 923–932.
[43] D.K. Bucar, L.R. Macgillivray, J. Am. Chem. Soc. 129 (2007) 32–33.
[44] M.D. Luque De Castro, F.P. Capote, Analytical applications of ultrasound,
Techniques and Instrumentation in Analytical Chemistry, Elsevier,
Amsterdam, The Netherlands, 2007, p. 26.
[45] Li, H. Li, Z. Guo, Y. Liu, Ultrason. Sonochem. 13 (2006) 359–363.
[46] S. Devarakonda, J.M.B. Evans, A.S. Myerson, Cryst. Growth Des. 3 (2003) 741–
746.
[47] Y.Y. Gao, C. Xie, J.K. Wang, Mater. Res. Innov. 13 (2) (2009) 112–115.
[48] A.E. Neilson, S. Sarig, J. Cryst. Growth 8 (1971) 1–7.
[49] A.C. Zettlemoyer, Nucleation, Marcel Dekker, Inc., 1969 (p. 71).