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CHEMICAL ENGINEERING TRANSACTIONS 

VOL. 56, 2017 

A publication of 

The Italian Association 
of Chemical Engineering 
Online at www.aidic.it/cet 

Guest Editors: Jiří Jaromír Klemeš, Peng Yen Liew, Wai Shin Ho, Jeng Shiun Lim
Copyright © 2017, AIDIC Servizi S.r.l., 
ISBN 978-88-95608-47-1; ISSN 2283-9216

Effect of Blumea Balsamifera Extract in the Kinetics of 
Calcium Oxalate Crystallisation 

Charlimagne M. Montealegre*, Allieson C. Ilao, Raphael Victor T. Mendoza, 
Ray Paulo M. Carpio, Rizalinda L. de Leon 

Department of Chemical Engineering, University of the Philippines Diliman, Quezon City Philippines 1101  
cmmontealegre@up.edu.ph 

Calcium oxalate stones comprise a large number of kidney stone cases. Kidney stone treatment with 
medicinal herbs such as Blumea balsamifera (B. balsamifera) had been practiced traditionally. In this study, 
the effect of B. balsamifera extract on the crystallisation of calcium oxalate was determined by modelling Ca2+ 
concentration in solutions. Crystallisation was performed by mixing equal concentrations of Ca2+ and C2O4

2- at 
200 rpm and supersaturations of 20, 25, 30, 35 and 40. Ca2+ concentration was measured using 
potentiometry. A second order kinetic model best fitted the concentration-time data with an average correlation 
coefficient of 0.9759 ± 0.0155. The rate constant is increased by the presence of the extract with a maximum 
increase of 6,460 % from 0.0152 ± 0.0079 ppm-1 s-1 to 0.9993 ± 0.5524 ppm-1 s-1 at a supersaturation of 30 
and 0.5 mg/mL of extract. The minimum increase in rate constant was observed at supersaturation of 25 and 
1.0 mg/mL of extract from 0.0088 ± 0.0058 ppm-1 s-1 to 0.0120 ± 0.0020 ppm-1 s-1 corresponding to a 36.71 % 
change. The extract increased the rate of crystallisation, consistent with the findings from other studies using 
different approaches. An increased crystallisation rate would favour the formation of smaller crystals that are 
easily eliminated from the urinary system. 

1. Introduction

Calcium oxalate is an inorganic salt found in almost all types of kidney stones (Kirejczyk et al., 2014) and in 68 
% of documented cases, identified calcium oxalate as the main component of the stone (Hughes, 2007). 
Amongst the treatments for kidney stones are extracorporeal shock-wave lithotripsy, ureteroscopic extraction, 
and percutaneous nephrolithomy (Bushinsky, 2016). Though some of these are non-invasive, treatment cost 
is high. Nowadays, the herbal remedies for renal stones are gaining popularity. Several studies explored the 
effect of herbal extracts on the crystallisation process of calcium oxalate. The average size particles of 
precipitates significantly decreased due to the addition of extracts from Desmodium styracifolium, Orthosiphon 
stamineus and Cystone during in vitro crystallisation (Rodgers et al., 2014). Extracts of Achyranthes indica 
Linn (Pareta et al., 2011) and Bergenia ciliata (Saha and Verma, 2013) showed inhibition of nucleation and 
aggregation of calcium oxalate monohydrate (COM) crystals and favoured the formation of COD crystals. 
In the Philippines, Blumea balsamifera (B. balsamifera), locally known as Sambong, is promoted by the 
Philippine Department of Health as a diuretic and medicine for dissolution of kidney stones (Oyson, 2013). 
There are researches confirming its effectiveness as a diuretic and in the dissolution. One of these claimed 
that B. balsamifera extract has maximum chemolytic effects at 40 mg/d dose (Rico, 1992). However, the effect 
of B. balsamifera in the kinetics of kidney stones formation is unknown. 
The rate of a reaction limited system is determined by the reaction between Ca

2+ and C2O4
2-. For equimolar 

concentrations of calcium and oxalate ion, the rate law is written as Eq(1), here the order is n = 2 for an 
elementary reaction and n ≠ 2 for non-elementary reactions. 

−dCadt 	= 	k[Ca ][C O ] = 	k	[Ca ]  (1) 

 

   

DOI: 10.3303/CET1756273

 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 

Please cite this article as: Montealegre C.M., Ilao A.C., Mendoza R.V.T., Carpio R.P.M., Leon R.L.D., 2017, Effect of blumea balsamifera 
extract in the kinetics of calcium oxalate crystallization, Chemical Engineering Transactions, 56, 1633-1638  DOI:10.3303/CET1756273  

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The crystallisation of calcium oxalate was well studied in the literature. Among the earliest proponents of 
kinetic studies were Nancollas and Gardner (1974) who established the second order dependence of the 
kinetic equation on concentration. Various studies confirmed the early observations by Nancollas and Gardner 
in systems with and without inhibitors (Grases et al., 1989) and in surface controlled systems (Öner et al., 
2015). Even recent studies confirmed this but with limitations. Kassemi et al. (2011) used a combined 
transport-kinetics model to study the crystallisation of renal calculi. They reported that surface reaction kinetics 
is limiting at low supersaturation and low Damköhler number but for higher supersaturations and large 
Damköhler number, and as the crystal size increases, transport limitations are more likely. 
The effect of different compounds on the kinetics of crystallisation was also studied. Ions of magnesium, zinc, 
copper, and manganese as well as copper complexes of citrate and EDTA reported inhibition of crystallisation 
(Grases et al., 1989). Biomolecules such as transferrin, bovine serum albumin, chondroitin sulfate (Farmanesh 
et al., 2014), phosphate-containing biological compounds (Grases et al., 1990), and various plant extracts 
(Rodgers et al., 2014) also reported inhibition on calcium oxalate crystallisation kinetics. 
This study aims to model the crystallisation kinetics of calcium oxalate in equimolar Ca

2+ and C2O4
2- solutions 

based on the Ca2+ concentration profile and to determine the effect of B. balsamifera extract on the kinetics of 
crystallisation. 

2. Methodology 

2.1 Design of Experiment 

To investigate the crystallisation kinetics of and to determine the effect of B. balsamifera extract on the 
crystallisation, two factors were varied: initial supersaturation and extract concentration in the solution. The 
initial supersaturation was varied from 20, 25, 30, 35, and 40. These initial supersaturations were based on 
the solubility product of calcium oxalate monohydrate at 25 °C and calculated from Eq(2): 

S	 =	 [Ca ] C O 	K , 	°  (2) 
The concentrations of calcium and oxalate ions were maintained as 1 : 1 ratio to avoid immediate formation of 
calcium oxalate dihydrate crystals. The solubility product used in a study (Jung et al., 2005), Ksp = 2 × 10

-9 M2, 
was adapted. The extraction concentration was varied from 0 mg/mL, 0.5 mg/mL, and 1.0 mg/mL. These 
concentrations refer to the mass of dried leaves over the final volume of the calcium oxalate solution. 

2.2 Extract Preparation 

B. balsamifera leaves were dried at 40 °C for 6 d. The dried leaves were crushed using mortar and pestle, and 
load in a Soxhlet extractor with 99.5 vol% ethanol. The extraction was run for 12 h. After the extraction, 
ethanol was evaporated and deionised water was added. The stock solution was then filtered using Watman 
filter paper to remove unnecessary solids. 

2.3 Potentiometry 

Eutech 700 (pH/mV/°C/°F Bench meter) and Cole-Parmer
TM Calcium combination electrode were used for 

obtaining potential reading. The voltage reading was transmuted to concentration by a calibration curve 
constructed by plotting the potential readings of Ca2+ solutions having different concentrations. The 
relationship between Ca2+ concentration and mV reading is expressed in Eq(3) (Grases et al., 1989): mV	 = 	a	ln Ca 	+ 	b	 (3) 
Required amounts of Na2C2O4 and CaCl2 solution were prepared to have a 200 mL calcium oxalate solution. 
Then, the CaCl2 solution and 1 mL of extract were put in a 250 mL beaker. The solution was constantly mixed 
at 200 rpm. After the millivolt reading was constant, the Na2C2O4 solution was added. The millivolt readings 
were recorded in 10-second intervals for 30 min. The equation obtained from the calibration was used to 
convert the millivolt readings into calcium concentrations. 

3. Results and Discussion 

The potential readings from the Ca2+ selective electrode is converted into Ca2+ concentration. These are then 
used to determine the kinetic model which best describes the concentration profile of calcium oxalate 
crystallisation. A typical Ca2+ concentration profile is shown in Figure 1. 

1634



 

Figure 1: Calcium ion concentration profile for an initial supersaturation of 20, 30 and 40 

The start of the concentration profile shows an increasing calcium concentration. This is counter intuitive since 
for a reacting system, the concentration should decrease. This increase in concentration reflects the time 
delay of the calcium electrode used. The time delay in measurement is a limitation of the potentiometric 
method. This is minimised by adjusting the start of curve fitting at t = 30 s. 
The fit of the nth order kinetic model was assessed at varying reaction orders from 1 to 2.1. The correlation 
coefficients are summarised in Figure 2 which showed a satisfactory fit from 1.8 until 2.1. This suggests a 
second order reaction i.e. an elementary reaction between calcium and oxalate ions. This is consistent with 
various literature data on calcium oxalate crystallisation where the reported reaction order is 2 (Öner et al., 
2015).  

 

Figure 2: The correlation coefficient increased as the reaction order approaches 2 suggesting a second order 
reaction mechanism that is consistent with previous literature findings 

The second order reaction fitted the data satisfactorily with an average correlation coefficient of 0.9759 ± 
0.0155 across all degrees of supersaturation. The rate constants were calculated from the fit of the model and 
are summarised in Figure 3. The rate constant shows a strong dependence on supersaturation. Theoretically, 
reaction rate constants are only functions of temperature. However, in writing rate laws in terms of 

0

0,5

1

1,5

0 500 1.000 1.500 2.000

[C
a

2
+
] 

, 
p

p
m

t, s

S = 20 S = 30 S = 40

0,80

0,82

0,84

0,86

0,88

0,90

0,92

0,94

0,96

0,98

1,00

1,0 1,2 1,4 1,6 1,8 1,9 2,0 2,1

C
o
rr

e
la

tio
n
 c

o
e
ff
ic

ie
n
t

Reaction order

S = 20 S = 25 S = 30 S = 35 S = 40

1635



concentration, the rate constant is grouped with activity coefficients. In changing the supersaturation from 20 
to 40, the ionic strength of the solution also changes and this will affect the activity of the ions. 
 

 

Figure 3: The second order reaction rate constant increase with supersaturation which shows the dependence 
of the rate constant to the activity coefficient of the reactants 

 

Figure 4: The effect of the extract on the rate constant had different extents depending on supersaturation.  

0,0080 0,0088
0,0152

0,0474

0,1002

0,00

0,02

0,04

0,06

0,08

0,10

0,12

20 25 30 35 40

R
a
te

 c
o
n
st

a
n
t,
 p

p
m

-1
s-

1

Supersaturation ratio

0
,0

0
8
0

0
,0

2
8
9

0
,0

0
6
0

0,000

0,005

0,010

0,015

0,020

0,025

0,030

0,035

S20

R
a
te

 c
o
n
st

a
n
t,
 p

p
m

-1
s-

1

0
,0

0
8
8

0
,0

8
3
8

0
,0

1
2
0

0,00

0,01

0,02

0,03

0,04

0,05

0,06

0,07

0,08

0,09

S25

R
a
te

 c
o
n
st

a
n
t,
 p

p
m

-1
s-

1

0
,0

1
5
2

0
,9

9
9
3

0
,0

8
8
5

0,0

0,2

0,4

0,6

0,8

1,0

1,2

S30

R
a
te

 c
o
n
st

a
n
t,
 p

p
m

-1
s-

1

0
,0

4
7
4

1
,5

1
8
6

0
,6

1
0
9

0,0

0,2

0,4

0,6

0,8

1,0

1,2

1,4

1,6

S35

R
a
te

 c
o
n
st

a
n
t,
 p

p
m

-1
s-

1

0
,1

0
0
2

0
,9

5
2
4

0
,9

2
4
6

0,0

0,2

0,4

0,6

0,8

1,0

1,2

S40

R
a
te

 c
o
n
st

a
n
t,
 p

p
m

-1
s-

1

0 mg/mL

0.5 mg/mL

1.0 mg/mL

1636



The effect of the presence of the extract was studied using a similar approach. The fit of the second order 
reaction was satisfactory with a minimum value of 0.9256 ± 0.0093, a maximum of 0.9935 ± 0.5524 and an 
average of 0.9731 ± 0.0193. The rate constants are summarised in Figure 4. The rate constant generally 
increased especially at 0.5 mg/mL of extract. 
In the presence of the extract, the rate constants generally increased except at a supersaturation of 20 and 
1.0 mg/mL of extract. At 0.5 mg/mL of extract, the rate constant increased remarkably with a minimum 
percentage increase of 260 % at S = 20 and a maximum increase of 6,460 % at S = 30. The changes are 
smaller at 1.0 mg/mL of extract, with a minimum increase of 36.7 % at S = 25 and a maximum of 1,188 % at S 
= 35. 
The kinetic model resulted into a reaction order of 2 that is elementary and consistent with the literature data 
from studies using chemical activity (Nancollas and Gardner, 1974), systems with other inhibitors (Grases et 
al., 1989), and in surface controlled systems (Öner et al., 2015). The rate constants increased with increasing 
supersaturation. This is possibly an effect of the increased activity coefficient due to increased ion 
concentration. The model showed that in the presence of B. balsamifera extract, the rate constant of the 
reaction increased and crystallisation is promoted. Metal ions, citrate and EDTA complex (Grases et al., 
1989), phosphate-containing compounds (Grases et al. 1990), aspartic acid (Grases et al., 1988), chondroitin 
sulfate, serum albumin, and transferrin (Farmanesh et al., 2014), and other plant extracts (Rodgers et al., 
2014) reported an inhibition of crystal nucleation and growth, contrary to the results of this study. However, the 
observed increase in the crystallisation rate constant is consistent with a thermodynamic study on the effect of 
B. balsamifera extract on nucleation of crystals (Montealegre and De Leon, 2016) which also reported an 
increase in nucleation rate, and a decrease in the size of the crystals (Montealegre and De Leon, 2016). 

4. Conclusions 

The crystallisation of calcium oxalate from equal concentrations of Ca2+ and C2O4
2- at degrees of 

supersaturations ranging from 20 to 40 was described by a second order kinetic model. The rate constant 
showed a dependence on the degree of supersaturation. B. balsamifera extract increased the rate constant by 
up to 6,460 %. This kinetic study supports the conclusion of a thermodynamic study which reported that the 
extract increased the crystallisation of calcium oxalate by an increased nucleation rate. Increasing the 
crystallisation rate is beneficial to kidney stone forming individuals since a large amount of small crystals that 
is easily eliminated is favoured instead of formation of large and pathological crystals. 

Acknowledgments  

The authors would like to thank Engineering Research and Development for Technology (ERDT) for the 
financial support of this study. 

Reference  

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