Pharmacology & Pharmacy, 2011, 2, 42-46
doi:10.4236/pp.2011.21005 Published Online January 2011 (http://www.SciRP.org/journal/pp)
Microwave Assisted Synthesis and Evaluation of
Cross-Linked Carboxymethylated Sago Starch as
Superdisintegrant
Akhilesh V. Singh1, Lila K. Nath1, Manisha Guha2, Rakesh Kumar1
1Department of Pharmaceutical Sciences, Dibrugarh University-Dibrugarh, Assam, India; 2Grain Science and Technology Depart-
ment, CFTRI, Mysore, Karnataka, India.
Received October 20th, 2010; revised November 17th, 2010; accepted December 13th, 2010
ABSTRACT
The aim of this study was to modify the sago starch and evaluate its efficacy as tablet disintegrant. Cross-linked car-
boxymethylated sago starch (CMSS) was synthesized using native sago starch (SS) and monochloroacetic acid (MCA)
with sodium hydroxide in microwave radiation environment. FT-IR analysis of the sample confirmed the carboxy-
methylation by showing absorpt i on peak at 1607.2 cm -1. CMSS with degree of substitution (DS) of 0.31 was formed and,
it was further evaluated as disintegrant in Ondasetron based tablets. The results revealed that CMSS could be used as
disintegrant in tablet formulation in concentration dependant manner.
Keywords: Sago Starch, Carboxymethylation, Disintegrant, SEM, FT-IR
1. Introduction
Starch is one of the most important and abundant plant
polysaccharide next to cellulose and chitin. Starch is
found primarily in the seeds, fruits, tubers, and stem pith
of plants, most notably corn, wheat, rice, sago, and pota-
toes. Starch derivatives play vital roles in the promising
biopolymers industries. This is because they are cheap,
non-toxic, renewable and biocompatible with many other
materials for industrial applications. Starches are em-
ployed in food, pharmaceutical and allied industries be-
cause of its good thickening and gelling properties.
Starches can be modified by chemical, physical and en-
zymatic methods for their tailor made use in different
form [1]. They are mainly used as binder, filler, emulsion
stabilizer, consistency modifier and disintegrantss.
Crosslinked sodium carboxymethyl starch which is also
known as sodium starch glycolate is extensively used in
fast dissolving tablets to disperse the drugs within short
span of time and deliver the active drug in the systemic
circulation of the body.
In a number of earlier reported methods, carboxy-
methylation of starch has been done using strong NaOH
and Mono chloroacetic acis (MCA) in aqueous/organic
medium at elevated temperature. It has been shown that
when a mixture of starch with sodium hydroxide and
monochloroacetic acid is irradiated, the carboxymethyl
starch obtained consists of fractions with high levels of
carboxymethyl groups and fractions with a predominant
content of carbonyl groups [2]. Earlier some workers
have modified yam starch and evaluated its efficacy as
tablet disintegrant [3]. In our laboratory recently we have
synthesized carboxymethylated derivative of moth bean
starch by conventional method and evaluated as su-
perdisintegrant [4]. Microwave assisted synthesis is an
efficient and novel technique used in polymer synthesis.
Microwave-assisted synthesis has attracted huge interest
in recent years among researchers due to its rapid transfer
of energy in the bulk of the reaction, as well as short re-
action time.Compared with the conventional approach a
microwave-assisted reaction has advantages of energy
saving, high conversion, and rapidity [5,6] .
The sago palm (Metroxylon sagu Rottb.) is grown well
in the tropical rain forests of Southeast Asia. This palm
contains nearly 20-45% starch on dry weight basis in its
trunk and it is one of the potential underutilized palms
[7].
This study was designed to synthesize the crosslinked
carboxymethyl derivative of sago starch, and evaluate its
efficacy as disintegrant in pharmaceutical formulation.
Ondasetron was chosen as model drug.

Microwave Assisted Synthesis and Evaluation of Cross-Linked Carboxymethylated Sago Starch as Superdisintegrant 43
2. Material and Methods
2.1. Materials
Sodium starch glycolate and POCl3 was procured from
Lobachemie, India. Ondasetron HCl was kindly donated
by Comed Pharmaceuticals Limited, Baddi, India. Mono-
chloro acetic acid (CDH, India) and Sodium hydroxide
(Merck, India) were procured and used without further
purification. Sago starch was procured from local market
of Chennai, Tamilnadu, India. All other chemicals re-
ceived were of AR grade and used without further puri-
fication.
2.2. Methods
2.2.1. Modi fi cation of Sag o Sta rch
Carboxymethylation of Sago starch (SS) was carried out
by following slight modified method described elsewhere
[8-10]. In this method Sago starch (4 g), NaOH (3.2 g)
and monochloroacetic acid (4 g) were taken in a beaker,
with 20 ml of Isopropyl alcohol and water (50:50) and
the contents were subjected to continuous stirring to ho-
mogeneity. Subsequent reaction was allowed to proceed
at varying temperature (from 25˚C to 70˚C and duration
of reaction (from 1 to 4 min) in the Microwave oven
(Model No.CE1111TL, Samsung Electronics, India). The
reaction products were precipitated with ethanol and
washed alkali free and dried in a vacuum oven at 45˚C
for 8 h. The reaction takes place in following manner:
NaOH
St-OH + CH2Cl-COOH St-O-CH2COOH +
NaCl + H2O
(1)
Finally dried powder was further cross-linked with
Phosphorous oxychloride (POCl3) to get the cross-linked
Na-carboxymethylated sago starch (CMSS).
2.2.2. Degree of Substitution
The DS of carboxymethylated sago starch (CMSS) was
determined by the method reported elsewhere [11].The
carboxymethyl groups in the CMSS were first converted
to an acid form with acid (HCl). The acidified starch was
then recovered by precipitation with methanol, filtration,
washing with methanol, and drying. Then, 0.2 M NaOH
(20 ml) was added to a suspension of accurately weighed
CMSS in 30 ml of purified water. The mixture was
transferred to a 100-ml volumetric flask and adjusted to
the mark with purified water. The solution (25 ml) was
transferred to an Erlenmeyer flask and titrated with 0.04
M HCl using phenolphthalein as the indicator. The titra-
tion was repeated three times, and the average value of
HCl volume was used for the calculations. A blank was
also titrated. The DS was calculated using following
equations:
162 nCOOH
Degree of substitutionMDS-58 nCOOH

 (2)


water
1W
MDS MS
100

 (3)


bHCl
nCOOHVV C 4

  (4)
where 162 is the molar mass of AGU (g/mol); nCOOH
(mol) is the amount of COOH; MDS (g) is the mass of
dry sample; MS (g) is sample mass: Wwater (%) is the
water content; Vb (ml) is the volume of HCl used for the
titration of the blank; V (ml) is the volume of HCl used
for the titration of the sample; CHCl (mol/L) is the HCl
concentration.
2.2.3. Scannin g Elec tr on Microscopy
Each starch samples were firstly air dried, and then
coated with gold. The prepared starch samples were
viewed under scanning electron microscope (JEOL, Ja-
pan).
2.2.4. FT-I R Study
Both native and carboxymethylated starch sample (5 mg)
were blended with solid KBr, (Merck, Germany) and
about 40 mg blend was used to prepare a pellet (Hydrau-
lic pellet press KP, Mumbai, India).The spectra were
scanned from 4000-400 cm-1 in a Perkin Elmer FT-IR
spectrometer(Perkin Elmer, USA) under dry air at room
temperature.
2.2.5. Swelling Capacity
The swelling capacity of the native SS, CMSS and SSG
was estimated by slightly modified method of [12]. In
this method the tapped volume occupied by 10 gm of the
powder (Vx), was noted and the powder was dispersed in
85 ml of distilled water and the volume made up to 100
ml with distilled water. After 24 h of standing, the vol-
ume of the sediment (Vv) was measured. The swelling
capacity was then computed as the ratio of Vv/Vx.
2.2.6. Hydrati on C ap aci t y
The slight modified method [13] was used for this study.
A 10 gm was placed in each of four 15 ml plastic centri-
fuge tubes to which 10 ml of distilled water was added
and then stoppered. The contents were mixed on a cyc-
lomixer for 2 min. The mixture was allowed to stand for
10 min and then centrifuged at 1000 rpm for 10 min on
absented centrifuge.
The supernatant was carefully decanted, and the sedi-
ment was weighed. The hydration capacity (Hc) was then
calculated using the equation:
Sediment weight
Hc =Dry sample weight (5)

Microwave Assisted Synthesis and Evaluation of Cross-Linked Carboxymethylated Sago Starch as Superdisintegrant 44
2.2.7. Viscosity Determination
Viscosity of all the samples were carried out using
Brookfield Viscometer (Brookfield Engineering Labora-
tory, USA) at 25˚C, using spindle no 92 at 6 rpm h-1. The
concentration of all the samples were kept at 10%w/v.
2.2.8. Tablet Formulation
Eight batches of the tablets were prepared using direct
compression method. Four batches (F1-F4) contain
CMSS; and other four (F5-F8) contains SSG as su-
perdisintegrant in the ratio of 2, 4, 6 and 8%w/w respec-
tively. All ingredients were mixed properly and then
powder blend was compressed into tablets using a
ten-station tablet compression machine (Shakti Engi-
neering, Ahmedabad, India).
2.2.9. Evaluation of Tablets
All the tablets were evaluated for hardness, friability,
drug content and percentage weight variation. To evalu-
ate the efficiency of carboxymethylated sago starch as
disintegrant in pharmaceutical formulation, the synthe-
sized CMSS was evaluated and compared with estab-
lished superdisintegrant i.e. Sodium starch glycolate at 2,
4, 6 and 8% w/w concentration as disintegrant in On-
dasetron based tablets. The in vitro disintegration study
was carried out using USP disintegration apparatus (Tab
Machine, Mumbai, India).
3. Results and Discussions
Carboxymethylated sago starch with different DS was
prepared using MCA and sodium hydroxide in reaction
medium of isopropyl alcohol/water. The optimization of
carboxymethylation reaction was performed by varying
two reaction parameter i.e. reaction temperature and du-
ration of reaction. Each parameter is varied keeping other
constant. The influence of these parameters on DS was
followed experimentally.
3.1. Influence of Temperature and Duration of
Reaction on Carboxymethylation
The influence of reaction temperature on DS is shown in
Figure 1. The DS of CMSS increases with varying the
temperature. The highest DS value (0.31) was obtained at
55˚C and it decreases further, this could be due to change
in its confirmation or, due to degradation. Further all
investigations were carried out at 55˚C, since it produced
highest DS.
The duration of reaction was varied from 1 to 4 min.
The value of DS obtained at different time points are
shown in Figure 2. It can be seen that DS value increases
with reaction time and further decreases, it might be due
to degradation of this polymer. The surface texture of the
sago starch is somewhat oval shaped (Figure 3) but after
Figure 1. Influence of reaction temperature on DS.
Figure 2. Influence of duration of reaction on DS.
cross-linking the surface texture has been somewhat dis-
oriented that can be seen in Fi gu re 4.
3.2. Physicochemical Character
The addition of carboxyl group is indicated by presence
of an absorption peak band at 1607.2 in the FT-IR spec-
trum of CMSS which is not present in native sago starch
(shown in Figure 5).The swelling power of the starches
is presented in Table 1. The decreasing order of the
swelling power was SSG ≈ CMSS > SS. The Swelling
power of the starches was due to the amylopectin portion
and concentration in the starch granules. Water penetra-
tion into the starch granules may be increased due to hy-
drophilic nature of carboxymethyl group, which resulted
into swelling of the starch granules, and dissolution in
water. Carboxymethylation decreases the amylose con-
tent in starch by destruction of helical structure of amy-
lose. Similarly comparative hydration capacity is shown
in Table 1, SSG had high hydration capacity as com-
pared to CMSS and SS. This may be due to different DS
value of carboxymethylation and amylose/amylopectin
ratio and arrangement in starch. The hydration value of
CMSS and SSG is more as compared to SS; it may be
due to addition of negatively charged carboxymethyl
group as well as alkalinization of starch [14].

Microwave Assisted Synthesis and Evaluation of Cross-Linked Carboxymethylated Sago Starch as Superdisintegrant 45
Figure 3. Scanning electron micrograph of native sago starch.
Figure 4. Scanning electron micrograph of carboxymethy-
lated sago starch.
Figure 5. FT-IR spectra of native and modified sago starch.
3.3. Tablet Evaluation
All the prepared tablets were evaluated for physical
characterization and data shown in Table 2. The results
were found within the official limits. Tablets containing
different concentration of CMSS and SSG were evalu-
ated for disintegrant property (shown in Figure 6). Car-
boxymethylation of starch increases its cold-water hy-
drophilicity due to addition of negatively charged func-
tional group (CH2COO-) in the parent chain of native
starch. The less concentration of CMSS possesses insuf-
ficient swelling power to break the tablets. The tablets
containing higher conc. (6% w/w) CMSS showed nearly
comparable disintegration time as shown by SSG based
tablets. At higher conc. (8% w/w) the disintegration time
of both the tablets, mainly SSG based was decreased that
may be due to formation of viscous gel mass which im-
pede the penetration of water in to the tablets and re-
tarded the disintegration power. The use of CMSS as a
tablet disintegrant in this study seemed to have the opti-
mum concentration at 8 %w/w.
Table 1. Comparative swelling, hydration and viscosity
behavior of all starches.
Starch TypeSwelling
capacity Hydration capacity Viscosity (cps)
Sago Starch1.6 ± 0.10 0.68 ± 0.15 61343
CMSS 4.0 ± 0.21 2.2 ± 0.10 74012
SSG 4.2 ± 0.25 2.4 ± 0.25 75643
All the values are represented as Mean ± SD; and n = 3.
Table 2. Physical Evaluation of tablets.
Batch Hardness
(kg/cm2) Friability (%) Drug content (%) % Weight deviation
F1 4.6 ± 0.25 0.35 ± 0.26 97.35 ± 0.35 1.3 ± 0.18
F2 4.7 ± 0.37 0.33 ± 0.15 98.26 ± 0.20 1.0 ± 0.28
F3 4.3 ± 0.26 0.44 ± 0.21 99.13 ± 0.21 2.5 ± 0.20
F4 5.2 ± 0.31 0.53 ± 0.40 98.33 ± 0.26 2.7 ± 0.15
F5 4.9 ± 0.25 0.34 ± 0.35 99.43 ± 0.23 2.1 ± 0.35
F6 5.0 ± 0.22 0.22 ± 0.25 97.32 ± 0.20 2.4 ± 0.14
F7 5.2 ± 0.30 0.39 ± 0.16 98.48 ± 0.30 2.9 ± 0.20
F8 5.1 ± 0.10 0.36 ± 0.24 97.98 ± 0.34 2.1 ± 0.12
All the values are represented as Mean ± SD; and n = 3.

Microwave Assisted Synthesis and Evaluation of Cross-Linked Carboxymethylated Sago Starch as Superdisintegrant 46
Figure 6. Comparative disintegration behavior in ondase-
tron based tablets.
4. Conclusion
CMSS was synthesized in microwave radiation environ-
ment with DS value of 0.31 using MCA and NaOH in
IPA/H2O solvent medium. The physicochemical values
are comparable to official superdisintegrant i.e. SSG, but
much higher than native sago starch. CMSS could be
used as a potential disintegrant in tablet dosage form at
higher concentration (8% w/w).
5. Acknowledgement
The authors are thankful to Prof. Harkesh B Singh, De-
partment of Chemistry, IIT-Bomaby for carrying out
FT-IR of the samples, and also to IIT-Guwahati for
helping in SEM characterization.
REFERENCES
[1] O. B. Wurzburg, “Modified Starches: Properties and
Uses,” CRC-Press, Florida, 1984, pp. 4-15.
[2] O. S. Kittipongpatana, J. Sirithunyalug and R. Laenger,
“Preparation and Physicochemical Properties of Sodium
Carboxymethyl Mungbean Starches,” Carbohydrate Poly-
mer, Vol. 63, No. 1, 2006, pp. 105-112.
doi:10.1016/j.carbpol.2005.08.024
[3] N. Nattapulwat, N. Purkkao and O. Suwihaayapan,
“Preparation and Application of Carboxymethyl Yam
(Dioscorea Esculenta) Starch,” AAPS PharmSciTechnol-
ogy, Vol. 10, No. 1, 2009, pp. 193-198.
doi:10.1208/s12249-009-9194-5
[4] A. V. Singh, L. K. Nath, R. D. Pandey and A. Das, “Syn-
thesis and Application of Moth Bean Starch as Superdis-
integrant in Pharmaceutical Formulation,” Journal of
Polymer Materials, Vol. 27, No. 2, 2010, pp. 173-177.
[5] V. Singh and A. Tiwari, “Microwave Accelerated Me-
thylation of Starch,” Carbohydrate Research, Vol. 343,
No. 1, 2008, pp. 151-154.
doi:10.1016/j.carres.2007.09.006
[6] A. N. Jyothia, K. N. Rajasekharanb, S. N. Moorthy and J,
Sreekumara, “Microwave Assisted Synthesis and Char-
acterization of Succinate Derivative of Cassava (Manihot
Esculenta) Starch,” Starch/Starke, Vol. 57, No. 11, 2005,
pp. 556-563. doi:10.1002/star.200500429
[7] Z. A. Noor Fadzlina, A. A. Karim and T. T. Teng, “Phys-
icochemical Property of Carboxymethyl Sago ( Metroxy-
lan Sagu) Starch,” Journal of Food Science, Vol. 70,
No. 9, 2005, pp. 560-567.
doi:10.1111/j.1365-2621.2005.tb08305.x
[8] S. Zeiko, J. J. Katarina and J. Slobodan, “Synthesis of
Carboxymethyl Starch,” Starch/Starke, Vol. 52, No. 11,
2000, pp. 413-419.
doi:10.1002/1521-379X(200011)52:11<413::AID-STAR
413>3.0.CO;2-B
[9] P. D. Pandya, N. K. Patel and V. K. Sinha, “Synthesis and
Characterization of Sodium Salt of Partially Carboxy-
methylated Starch,” International Journal of Polymeric
Materials, Vol. 51, No. 12, 2002, pp. 1081-1085.
doi:10.1080/714975698
[10] S. Kamel and K. Jahangir, “Optimization of Carboxy-
methylation of Starch in Organic Solvents,” International
Journal of Polymeric Materials, Vol. 56, No. 5, 2007, pp.
511-519. doi:10.1080/00914030600945770
[11] Z. Stojanovic, K. Jeramics, S. Jovanovic and D. M.
Lechner, “A Comparison of Some methods for the De-
termination of the Degree of Substitution of Carboxy-
methyl starch,” Starch/Starke, Vol. 51, No. 1, 2005, pp.
79-83. doi:10.1002/star.200400342
[12] A. O. Okhamafe, A. Igboechi and T. O. Obasaki, “Cellu-
loses Extracted from Groundnut Shell and Rice Husk. 1:
Preliminary Physicochemical Characterization,” Phar-
macy World Journal, Vol. 8, No. 4, 1991, pp. 121-123.
[13] S. S. Komblum and S. B. Stoopak, “A New Tablet Disin-
tegrant: Crosslinked Polyvinylpyrrolidine,” Journal of
Pharmaceutical Sciences, Vol. 62, No. 1, 1973, pp. 43-49.
doi:10.1002/ jps.2600620107
[14] M. I. Khalil, A. Hashem and A. Hebesish, “A Carboxy-
methylation of Maize Starch,” Starch/Starke, Vol. 42, No.
2, 1990, pp. 60-63. doi:10.1002/star.19900420209