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Formulation and Characterization of Modified Starch by Using Carboxy

Methylation Technique

Article · December 2012

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IJCIHI : Vol. 5, No. 2, July-December 2012, pp. 25-28, Published by Serials Publications, ISSN: 0973-7413

Formulation and Characterization of Modified Starch by Using

Carboxy Methylation Technique
Neelam Kavlani1, Vijay Sharma2*, and Lalit Singh3
1,2,3
DShri Ram Murti Smarak College of Engineering and technology, Pharmacy, Bareilly (U.P.)

ABSTRACT: Starch is a naturally occurring, biodegradable, inexpensive and abundantly available polysaccharide molecule.
In acetylation, hydrophilic hydroxyl groups are substituted with hydrophobic acetyl groups. Acetylation makes starch more
hydrophobic and prevents the formation of hydrogen bonding between hydroxyl groups and water molecules. The comparative
analysis of maize starch and carboxymethylated starch for their relative potential to act as a suitable binder in tablets was
studied. The friability study suggested that the tablets with modified starch possess greater strength. Also the disintegration time
for the sets of tablets containing CMMS was upto 30% less as compared to tablets containing MS. Greater solubility of CMMS
resultis into faster rupture of the tablet.
Keywords: Modified Starch Carboxy, Methylation, Maize Starch, Carboxy Methylated Maize Starch.

1. INTRODUCTION Chemical modification involves the introduction of

Starch is a naturally occurring, biodegradable, inexpensive
and abundantly available polysaccharide molecule. It is
widely distributed in the form of tiny granules as the major
reserve carbohydrate in stems, roots, grains, and fruits of
all forms of green leafed plants. Cereal grains, such as corn,
wheat, sorghum, and tubers, and roots, such as potato,
tapioca, arrowroot, etc., are some of the commercial sources
of starch for industrial exploitation. It consists of glucose
units (C6H10O5)n with n ranging from 300 to 1000. Starch is
composed of a mixture of two polymers called amylose and
amylopectin. Amylose is a linear polymer with molecular
weight of less than 0.5 million Dalton (degree of
polymerization of 15 × 102–6 × 103) depending on its
botanical source. Amylose macromolecules consist of
a-D-glucopyranose units joined by a- 1,4 acetal linkages.
Amylopectin molecules are much larger and highly branched
with molecular weight of 50 –100 million Dalton and degree
of polymerization of about 3 × 105–3 × 106. The molecules
contain a-1,4 linear bounds, and is branched through
a-1,6 linkages[1-2].
In addition to being a major food item, Starches, in
particular, have attracted considerable interest in diverse
applications such as biodegradable plastics, coatings,
adhesives, foams, flocculants, dispersing agents,
sequestering agents. However, in native state it exhibits
limited applications due to low shear stress resistance and
thermal decomposition, high retrogradation and syneresis,
in addition to poor processability and solubility in common
organic solvents.
*Corresponding Author: E-mail: vijaysrampur@gmail.com
functional groups into the starch molecule, resulting in
markedly altered physico-chemical properties. Such
modification of native granular starches profoundly alters
their gelatinization, pasting and retrogradation behavior. The
chemical and functional properties achieved when
modifying starch by chemical substitution depend, inter alia,
on starch source, reaction conditions (reactant concentration,
reaction time, pH and the presence of catalyst), type of
substituent, extent of substitution (degree of substitution,
DS1; or molar substitution, MS2), and the distribution of
the substituents in the starch molecule[3-7].
The carboxymethyl substitution of starch hydroxyl
groups gives rise to derivatives that are cold water-soluble.
To prevent starch gelatinization, the reaction has to be
carried out in an organic medium. Carboxymethyl starch,
under the name sodium starch glycolate, is used in the
pharmaceutical industry as a disintegrant and as a sizing
and printing agent in the textile industry. Highly substituted
derivatives are possible.[8]
In acetylation, hydrophilic hydroxyl groups are
substituted with hydrophobic acetyl groups. Acetylation
makes starch more hydrophobic and prevents the formation
of hydrogen bonding between hydroxyl groups and water
molecules. Since the tendency of an aqueous starch
dispersion to increase in viscosity on cooling and finally to
gel is related to the association of amylose molecules, a
treatment such as acetylation which retards or eliminates
this crystallization or retrogradation will effect stabilization
of the starch sol. Acetylation also prevents or minimizes
association of amylopectin outer branches. This is of
practical value in many industrial and food applications
because such associations can cause cloudiness and
syneresis in aqueous dispersions of starches[9].
26 Neelam Kavlani, Vijay Sharma, and Lalit Singh

2. MATERIAL AND METHOD Where Mo:molar mass of the anhydroglucose unit

= 162 g/mol; MR:molar mass of carboxymethyl residue
Materials = 58 g/mol; nNaOH: quantity of sodium hydroxide used
(mol); mp: weight of polymer taken (g); mc: corrected
The Following Ingredients Were Procured from the weight of polymer (g); F: moisture (%).
Respective Sources
Maize starch from Loba Chemie Pvt Ltd, FT-IR Spectroscopy
Monochloroaceticacid and NaOH from Rankem, RFLC The FTIR spectroscopic analysis was carried out using a
Limited; Paracetamol (PCM; Nutan Gujrat industrial estate, SHIMADZU spectrophotometer. Before analysis, the maize
Vadodara), dibasic calcium phosphate (New India Chemical starch and CMS samples were dried and stored in a
Enterprises, Kochi) and magnesium stearate (G. S. Chemical desiccator prior to preparation of KBr discs. Samples of
Testing Laband Allied Industries Bombay, India) were used 10 mg of starches were mixed with 90 mg of KBr and about
as the active drug, filler and lubricant, respectively. 20 mg of the mix was then used to compress (6 T) a thin
Disintegrants in this study was rice starch (S.D. fine chem.
disc of 9mm diameter. Spectra from 4000 and 400 cm–1 was
Ltd. Mumbai, India).
recorded at 4 cm–1 resolution for each sample.
Method for Preparation of Carboxymethylated Starch
Solubility
A quantity of 70 g of starch was suspended in 150 mL of
Cold water solubility was determined in accordance with
H2O, stirred at 50ºC and then 200mL of 1.7 M NaOH was
the method reported by Chen and Jane[10] with
added continuing the stirring for another 20 min at 50ºC.
A volume of 45 mL of 10 M NaOH and then 36g of modification. A 100 mL (0.5%, w/v) suspension of CMS
monochloroacetic acid (MCA) dissolved in minimal H2O was transferred into a blender jar and blended at low speed
volume, was added to the mixture and stirred for 1 h. The for 3 min. The starch suspension was then transferred to a
mixture was then neutralized with acetic acid and cooled at 250 mL centrifuge bottle and centrifuged at 1,200 × g for
room temperature. Salt ions were removed by washing the 15 min. A 50 mL aliquot of supernatant was taken into a
slurry with a solution of acetone/H2O (7:3, v/v) followed preweighed aluminum moisture can and dried in an air oven
by repeated filtration and resuspension. The slurry was then at 105ºC until the constant weight was obtained. Percent
precipitated with acetone, filtered and the CM-HAS was cold water solubility was then calculated.[10]
recovered. The material was dried in air overnight.
3. PREPARATION OF TABLETS
Method for Characterization of Carboxymethylated Paracetamol tablets using different starches (MS, CM-MS)
Starch were prepared using wet granulation method. The tablets
of 200 batch size each was punched using a single punch
Determination of Degree of Substitution machine (Cadmach U.K.).
Titrimetry was used for the determination of the DS by
dispersing CMS (10 g) in acetone (300ml) and then 5M HCl Table 1
(30 ml) was added to the dispersion and stirred for 30 min. Tablet Formulations Using Starch as Disintegrant
During this process, the CMS which was in sodium salt form FORMULATION Paracetamol Lactose MS CM-MS
was converted to the H-CMS (carboxymethyl starch in
hydrogen form). H-CMS was then washed four times with MS1 500 7.0 53.0 -
80% (v/v) methanol until the solution became neutral with MS2 500 33.5 26.5 -
pH test. The neutral dispersion was then filtered again, MS3 500 46.75 13.25 -
suspended in acetone and stirred for another 15 min, CMMS1 500 7.0 - 53.0
following which it will be filtered, and dried for 24 h in CMMS2 500 33.5 - 26.5
a desiccator over silica gel. Two grams of H-CMS CMMS3 500 46.75 - 13.25
was dissolved in 1% (w/v) NaCl solution and titrated with
1M NaOH solution.
4. EVALUATION OF TABLETS
The degrees of substitution is
nNaOH × M o Tablet Hardness
DS =
mc − nNaOH × M R The tablet hardness was determined on an electronic digital
hardness tester (Erweka, Germany). Ten tablets were
 mp F 
mc = m p −  measured individually. The mean values and standard
 100  deviation were calculated.[11]
Formulation and Characterization of Modified Starch by Using Carboxy Methylation Technique
Tablet Friability
The friability was conducted on twenty tablets using a
friability tester (Erweka, Germany). The drum was rotated
at 25 rpm for 4 minutes. Loss of tablet weight with respect
to the initial value was then calculated as percent friability.[11]
Disintegration Time
The disintegration time was determined according to the
disintegration test for uncoated tablets of The Indian
Pharmacopoeia (IP-1996). Six tablets were tested. One
tablet was placed in each of the six tubes of the basket and
operated of the apparatus. Distilled water was maintained
at 37 ± 2ºC as the immersion fluid. The average
disintegration time and standard deviation of six tablets were
determined.
Dissolution Test
The dissolution test of Paracetamol tablet followed the
monograph of PCM tablets in the USP XXII. In- vitro release
pattern in phosphate buffer (pH 7.4) were determined by
using apparatus 1 according to USP XXII and procedure
followed as described in USP XXII. Values of cumulative
percent drug dissolved at various time intervals were also
found out and plotted against time. Values of t50 (time for
50% dissolution) and t70 (time for 70% dissolution) and t90
(time for 90% dissolution) were determined from this plot.[12]
In-Vitro Drug Release
In-vitro release pattern in phosphate buffer (pH 7.4) will be
determined by using apparatus-1according to USP XXII.
Values of cumulative percentage of drug dissolved at various
time intervals will be analysed and plotted against time
values of t50 (time for 50% dissolution), t70 (time for 70%
dissolution) and t90 (time for 90% dissolution) will be
determined by this plot. [12]
5. RESULTS AND DISCUSSION
Mechanism of Reaction: The carboxymethylation process
could be considered by the following two reactions:
2ClCH2COOH + Na 2CO3 ⋅ H2O → 2ClCH 2COONa
+ CO2 + 2H2O (1)
St-OH + ClCH 2 COONa  NAOH St-OCH 2COONa
+ NaCl + H2O (2)
Eq. (1) represents the reaction between ClCH2COOH
and Na2- CO 3·H 2O to form ClCH 2COONa. In Eq. (2),
sodium hydroxide is required for the carboxymethylation
process, in an amount equivalent to the ClCH 2COONa.
NaOH acts as a multifunctional catalyst acting as:
(i) swelling agent, and (ii) etherifying agent. Thus, breaking
the H-bonds, consequently opening up the starch structure,
decreasing the crystallinity, making the starch molecule
more accessible to carboxymethylation, and guaranteeing
the penetration of the etherifying agents.
27
Characterization of Prepared CMMS
Degree of Substitution
It is defined as the average no of substituents per anhydro
glucose unit, AUG, the monomer unit of starch. Each AUG
contains 3 hydroxyl groups so the DS should lie between
0-3. During titrimetric study since 1.5 moles of NaOH were
utilized so the degree of substitution was found to be 0.7.
FTIR Spectra
The spectra of CMMS indicated the presence of carboxyl
functional group (a new peak at 1573.02 cm–1 corresponding
to carboxylated salt). This confirmed that carboxymethylation
has occurred.
Figure 1: FTIR Spectra of CMMS and MS
Solubility
It was found that the prepared CMMS is completely soluble
in cold water. The solution of the cold water soluble CMMS
is clear and its pH is 7. It is well known that introducing the
carboxymethyl group, in its sodium form (–CH2COONa),
to the starch molecule increases its solubility. The higher
the DS the higher is the solubility of the CMS. In the present
study, CMS with DS of about 0.7 is completely soluble in
cold water although this DS is not high. This might be an
indication of the superior even distribution of the etherifying
agents along the starch molecule in the initial stages of the
carboxymethylation. Consequently, a uniform distribution
of the carboxymethyl groups along the starch molecule
arises.
Formulation and Evaluation of Prepared Paracetamol
Tablets
On carrying the analytical study of prepared tablets using
MS and CM-MS the batch was found to give satisfactory
results. A summary of results can be accessed from Table 2.
The hardness test revealed the efficacy of the tablets to bear
the shear forces during transportation.
Also, the results of disintegration test clearly indicate
that the tablets prepared with CMMS disintegrate at a faster
rate as compared to those tablets prepared with MS which
suggests at the rate at which drug will be release from the
tablet is also faster in tablets containing the modified starch.
This result can be due to higher solubility of CMMS.
28 Neelam Kavlani, Vijay Sharma, and Lalit Singh

Table 2
Evaluation of Tablets Prepared Using Various Starches as Disintegrant

Batch Uniformity of Assay for % of Hardness Friability Disintegration Uniformity

weight labeled content (kg/cm2) ± SD % ± SD time of weight
MS1 593.4 ± 3.56 4.2 ± 0.40 101.33 ± 2.19 4.5 ± 0.02 0.5 ± 0.04 159 ± 7.09
MS2 596.3 ± 13.49 4.2 ± 0.33 104.00 ± 3.85 4.1 ± 0.02 0.4 ± 0.03 173 ± 3.33
MS3 595.5 ± 23.91 4.5 ± 0.51 98.60 ± 3.97 4.3 ± 0.02 0.7 ± 0.02 183 ± 4.20
CMMS1 598.3 ± 3.56 3.6 ± 0.03 102.60 ± 7.98 4.8 ± 0.09 0.2 ± 0.01 113 ± 5.05
CMMS2 596.5 ± 17.89 3.8 ± 0.29 101.33 ± 6.23 4.6 ± 0.06 0.2 ± 0.03 121 ± 4.87
CMMS3 596.5 ± 17.89 4.1 ± 0.40 98.60 ± 4.98 4.3 ± 0.05 0.12 ± 0.01 129 ± 3.23

In-Vitro Release Study than that of tablets with MS. Thus from the results it was
The study was conducted in phosphate buffer solution at concluded that the modified maize starch has got
37 ± 0.5ºC. Samples were taken every 5 min. The revealed better binding, dissolution property and dissolution
characteristics which can be exploited in future for
the time taken for the dissolution of 50, 70 & 90 % of the
commercial use.
drug has been summarized in Table 3. The results indicate
was carboxymethylated starch possesses better swelling References
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CMMS2 7.0 ± 0.59 12.9 ± 0.44 29.9 ± 0.71
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Figure 2: Dissolution Study of Prepared Tablets
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[8] M. Rahmouni, V. Lenaerts, D. Massuelle, E. Doelker, J.C.
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[10] Chen, J. and J. Jane: Preparation of Granular Cold-Water-Soluble
tablets containing CMMS was upto 30% less as compared Starches by Alcoholic- Alkaline Treatment. Cereal Chem. 71(6)
to tablets containing MS. This may be due to greater (1994), pp. 618-622.
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