Macromol. Symp. 2012, 313-314, 69–78 DOI: 10.1002/masy.201250308 69

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Development of Polyelectrolyte Complex

Microparticles for the Encapsulation of Isoniazid

Nirmala Devi,*1 Dilip Kumar Kakati,1 Tarun Kumar Maji2

Summary: Polyelectrolyte complex microparticles of different sizes were prepared by

optimising the ratio of chitosan and sodium carboxy methyl cellulose (SCMC). The

yield of the polyelectrolyte complex was dependent on the ratio of the two polymers

and the pH of the medium. % yield and viscosity measurements were carried out to

evaluate optimum pH and the ratio of the two polymers that produced the highest

yield. Effect of various factors like amount of surfactant, concentration of polymer on

the formation and size of the microparticles were investigated. The microparticles

formed were pH-responsive. These microparticles were used as carrier for isoniazid.

The loading efficiency and release behaviour of loaded microparticles were found to

be dependent on the amount of crosslinker used, concentration of drug and time of

immersion. Maximum drug loading efficiency was observed at higher immersion

time. The release rates of isoniazid at different pH were investigated and compared.

The sizes of the microparticles were investigated by scanning electron microscopy.

Microparticles were further characterised by FTIR and X-ray diffraction study. The

present work aims at producing microparticles as antitubercular drug carrier by using

chitosan and SCMC as polymers, glutaraldehyde as crosslinker and sunflower oil as

reaction medium.

Keywords: characterization; chitosan; crosslinking; polyelectrolyte complex; sodium

carboxy methyl cellulose

Introduction

Hydrogels are providing new opportunities

for a variety of medical application. Exam-

ples include the use of hydrogels as

skin substitutes, adhesives, scaffolds for

tissue engineering and matrices for

drug delivery.[1] New controlled drug

delivery systems in response to changes

in environmental conditions, such as

temperature,[2] pH,[3–4] light[5] and electric

field[6] have been explored. The chemical

modification of natural polymers is a

promising way for the development of such

epartment of Chemistry, Gauhati University,

uwahati-781014, India

mail: nimi262002@yahoo.co.in

epartment of Chemical Sciences, Tezpur Univer-

y, Napaam-784028, India

yright � 2012 WILEY-VCH Verlag GmbH & Co. KGaA

stimuli-responsive drug delivery systems

and to make good use of their inherent

biodegradability, biocompatibility and

nontoxicity. The major advantage of nat-

ural polymers includes their availability

and compatibility with the encapsulation

of wide range of drugs, with minimal use

of organic solvents.[7] Furthermore, bio-

adhesion, stability, safety and their

approval for human use are additional

advantages.[8]

Chitosan is a hydrophilic cationic

polyelectrolyte obtained by alkaline N-

deacetylation of chitin. Chitin is the most

abundant natural polymer next to cellulose

and is obtained from crab and shrimp

shells.[9] Chitosan has been broadly eval-

uated by the industries due to its biocom-

patibility and its potential use in controlled

release systems as membranes, tablets

and microspheres. Sodium carboxymethyl

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Macromol. Symp. 2012, 313-314, 69–7870

cellulose (SCMC) is an anionic derivative

of cellulose. They are, thus, expected to

interact and form polyelectrolyte complex

under controlled conditions.

While potentially curative treatments

have been available for almost half a

century, TB remains the leading cause of

preventable deaths and hence continues to

present a formidable challenge as a global

health problem. The World Health Orga-

nisation (WHO) estimates that approxi-

mately one-third of the global community is

infected with Mycobacterium tuberculosis

(TB), resulting in more than eight million

new cases and two million deaths annually.

Current short-term chemotherapy for

tuberculosis requires daily administration

of one or several antitubercular drugs

for a period of at least six months, which

leads to patient noncompliance and ther-

apeutic failure. Thus, tuberculosis (TB)

continues to be a leading cause of mortality

in spite of the availability of an effective

chemotherapeutic regimen.[10,11] The effi-

cient treatment of the disease is limited by

the toxicity of the drugs, the degradation of

drugs before reaching required zones in the

body, and low permeability of cell mem-

branes to the drugs.[12] As a rule, lipo-

somes,[13,14] polymers,[15,16] and microcon-

tainers[17] are used as antitubercular drug

carriers.

The purpose of this study was to

evaluate the polyelectrolyte complexation

conditions of chitosan and SCMC for

maximum yield and hence to produce

microparticles of chitosan-SCMC polyelec-

trolyte complex using glutaraldehyde as

crosslinker and employing the method of

water-in-oil emulsion (inverse emulsion).

These microparticles were used as carrier

for isoniazid, a potent antitubercular drug.

Besides, this process involves use of water

as a solvent and a vegetable oil (sunflower

oil) as emulsion medium to eliminate the

organic solvent particularly the most popu-

larly used paraffin oil.[18,19] Efforts are also

made to characterize and study the drug

encapsulation efficiency and release beha-

viour of microspheres under different

conditions.

Copyright � 2012 WILEY-VCH Verlag GmbH & Co. KGaA

Experimental Part

Materials

Chitosan, low molecular weight was pur-

chased from Sigma-Aldrich Inc. (USA).

SCMC (medium viscosity) was purchased

from Rankem (India).Glacial acetic acid

(E. Merck, India), tween 80 (E. Merck,

India) and glutaraldehyde 25% w/v (E.

Merck, Germany) were used as such

received. Isoniazid was purchased from

Sigma-Aldrich Inc. (USA). Edible grade

refined sunflower oil was purchased from

local market. DDI (double-distilled deio-

nised) water was used throughout the study.

Other reagents used were of analytical

grade.

Microparticle Preparation

Polyelectrolyte Complexation Conditions

Formation of a polyelectrolyte depends on

several parameters such as pH of the

polymer solutions, ratio between the poly-

mers, temperature etc. The optimal condi-

tions for the formation of polyelectrolyte

complex of chitosan/SCMC were evaluated

by determining the % yield at various ratio

of chitosan to SCMC and at various pH

conditions. The optimum ratio of chitosan

to SCMC and pH range at which maximum

complexation occurred were 1.0: 2.33 and

2.5–3.5 respectively. All the successive

experiments were performed at this

optimal pH and polymer ratio.

Preparation Procedure of Microparticles and

Microencapsulation

To a beaker containing a known amount of

(150 ml) sunflower oil, 30 ml of SCMC

solution (0.75–3% w/v) was added, under

stirring condition at 60� 1 8C to form an

emulsion. (0–1) g of the tween 80, dissolved

in 10 ml of water was added to the beaker to

stabilize the emulsion. A known amount of

(13 ml) chitosan solution of same concen-

tration (0.75–3% w/v) was added to the

beaker drop wise to attain complete phase

separation. However, the weight ratio of

chitosan to SCMC was maintained at 1:2.33

during all the experiments (judged by the

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Macromol. Symp. 2012, 313-314, 69–78 71

percent yield and viscosity). The pH of the

mixture was then brought down to 3.0–3.5

by adding glacial acetic acid solution. The

beaker containing the microparticles was

left to rest at this temperature for approxi-

mately 15 minutes. The system was then

brought to 5–10 8C to harden the micro-

particles. The cross linking of the polymer

microparticles was achieved by slow addi-

tion of certain amount of glutaraldehyde

(4.375–17.50 mmol/g of polymer) solution.

The temperature of the beaker was then

allowed to rise to 45 8C and stirring was

continued for another 3 hrs to complete the

crosslinking reaction. The microparticles

were filtered through 300-mesh nylon cloth,

washed with acetone to remove oil, if any,

adhered to the surface of microparticles.

This was further washed with distilled

water, and freeze-dried. The dried micro-

particles were then dipped in isoniazid

solution (0.5%–20%, w/v) for different

times (0.5–60 h), filtered through 300-mesh

nylon cloth, and quickly washed with water

to remove the surface adhered isoniazid.

The isoniazid-encapsulated microparticles

were again freeze-dried and stored in a

glass bottle in refrigerator.

Measurements

Measurement of Turbidity, Viscosity and

Coacervate Yield

In order to optimize the ratio of chitosan

and SCMC, the measurements of viscosity

and coacervate yield (%) are essential. The

mixing of chitosan and SCMC in different

ratios would produce solutions of different

turbidity. The optimal ratio at which

complete phase separation occurred

between chitosan and SCMC was the point

where the supernatant would have the

minimum viscosity. The viscosity of the

supernatant solution was measured by

using an ubbelohde viscometer at 30 8C.

Polymer in the supernatant solution would

be either negligible or absent when the

interaction between SCMC and chitosan

would be maximum. At this stage, the

viscosity of the supernatant would be close

or similar to the solvent viscosity.

Copyright � 2012 WILEY-VCH Verlag GmbH & Co. KGaA

The coacervate yield (%) obtained by

mixing of SCMC and chitosan in different

ratios was measured gravimetrically. The

coacervates remained after decantation of

supernatants were washed with distilled

water and then dried at 40 8C till the

attainment of constant weight.

Calibration Curve of Isoniazid

A calibration curve is required for the

determination of release rate of isoniazid

from the microparticles. A known concen-

tration of isoniazid in DDI water was

scanned in the range of 200–500 nm by

using UV visible spectrophotometer. For

isoniazid having concentration in the range

0.001 to 0.01 g/100 ml, a prominent peak at

261 nm was noticed. The absorbance values

at 261 nm obtained with the respective

concentrations were recorded and plotted.

From the calibration curve, the unknown

concentration of isoniazid was obtained by

knowing the absorbance value.

Loading Efficiency

A known amount of accurately weighed

microparticles was grounded in a mortar,

transferred with precaution to a volumetric

flask containing 100 ml of water (having

pH¼ 7.4, maintained by phosphate buffer

solution) and kept for overnight with

continuous stirring to dissolve the isoniazid

in the microparticles. The solution was

collected and the isoniazid inside the

microparticles was determined employing

UV spectrophotometer. The loading effi-

ciency (%), was calculated by using the

calibration curve and the following for-

mulae

Loading efficiency ð%Þ ¼ w1=w2 � 100

where

w1¼ amount of isoniazid encapsulated in a

known amount of microparticles

w2¼weight of microparticles

Drug Release Studies

Isoniazid release studies from the isoniazid-

encapsulated microparticles were carried

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Macromol. Symp. 2012, 313-314, 69–7872

out by using UV–visible spectrophotometer

(UV-2001 Hitachi). A known quantity of

microparticles was taken into a known

volume of water having different pH

(pH¼ 1.2 and 7.4). This pH was maintained

by using HCl and phosphate buffer solu-

tion. The content was shaken from time to

time and the temperature maintained

throughout was 30 8C (room temperature).

An aliquot sample of known volume (5 ml)

was removed at appropriate time intervals,

filtered and assayed spectrophotometrically

at 261 nm for the determination of cumu-

lative amount of drug release up to a time t.

Each determination was carried out in

triplicate. To maintain a constant volume,

5 ml of the solution having same pH was

returned to the container.

Water Uptake Study

The swelling behavior of chitosan-SCMC

microparticles were studied in two systems

at pH¼ 1.2 (0.1 N HCl) and pH¼ 7.4

(phosphate buffer). The microparticles

were immersed in either 0.1 N HCl at pH

1.2 or phosphate buffer at pH 7.4. The

weights of swollen microparticles were

determined for 60 hours.

The swelling behaviour was determined

by measuring the change of the weight of

the microparticles. The % water uptake for

each sample determined at time t was

calculated using the following equation.

Water uptake ð%Þ

¼ ½ðWt � W0Þ=W0� � 100

where Wt is the weight of the microparticles

after allowing to swell for a time (t), and W0

is the initial weight of the microparticles

before swelling. The experiments were

performed in triplicate and represented as

a mean value.

Scanning Electron Microscopy Study

The samples were deposited on a brass

holder and sputtered with platinum. Sizes

of the microparticles were studied at room

temperature using scanning electron micro-

scope (model JEOL, JSM-6390) at an

accelerated voltage of 15 kV.

Copyright � 2012 WILEY-VCH Verlag GmbH & Co. KGaA

Fourier Transform Infrared (FTIR) Study

FTIR spectra were recorded using KBr

pellet in a Nicholet (model Impact-410)

spectrophotometer. Chitosan, SCMC, poly-

electrolyte complex of chitosan and SCMC,

isoniazid, microparticles and isoniazid

loaded microparticles were each separately

finely grounded with KBr and FTIR spectra

were recorded in the range of 4000-

400 cm�1.

X-ray Diffraction Study

X-ray diffractograms of chitosan-SCMC

microparticles, isoniazid and microparticles

with isoniazid encapsulation were re-

corded on an X-ray diffractometer (Model

MiniFlex, Rigaku corporation, Japan). The

samples were scanned between 2u¼ 70

to 600 at the scan rate of 0.30/min.

Results and Discussion

The ratio between the chitosan and

SCMC was optimized by measuring the

coacervate yield (%), and viscosity of the

supernatant. Solutions of SCMC (0.5% w/

v) and Chitosan (0.5% w/v) were prepared

in acetic acid/sodium acetate buffer (pH

3.5). Both solutions were mixed in different

proportions to make 45 ml. The mixtures

were incubated at 40 8C for 24 hours and the

supernatant solution was separated. Coa-

cervate yield (%) of the precipitate and

viscosity of the supernatant were measured.

Each measurement was done in triplicate

and the results reported were the average

values.

Similarly to optimize the pH, solutions of

chitosan (0.5% w/v) and SCMC (0.5% w/v)

were prepared in DDI. Both the solutions

were mixed in the ratio of 1: 2.33: The pH of

the mixing solution was varied from 2.0–5.5

by using glacial acetic acid. Coacervate yield

(%) and viscosity of the supernatant was

measured.

Viscosity and Coacervate Yield

The plot of coacervate yield (%) against %

of chitosan is presented in Figure 1(a). The

coacervate yield (%) increased initially due

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Figure 1.

(a) Plot of coacervate yield (%) against % of chitosan

(b) Change in supernatant viscosity with variation in

percentage of chitosan in chitosan–SCMC mixture.

Figure 2.

Effect of variation of pH (2.0–5.5) on (a) % yield, (b)

Change in supernatant viscosity in chitosan–SCMC

mixture.

Macromol. Symp. 2012, 313-314, 69–78 73

to increase in interaction between chitosan

and SCMC, reached a maximum value

and then decreased. The maximum

yield (%) obtained when the interaction

between chitosan and SCMC was max-

imum and that was the point where the

percentage of chitosan in the mixture was

30–33%.

Change in supernatant viscosity with

variation in percentage of chitosan in

chitosan–SCMC mixture was shown in

Figure 1(b). Viscosity was found to

decrease initially, reaching a minimum

value, and after that it increased with

the increase in the percentage of chitosan.

The minimum viscosity observed when the

percentage of chitosan in the mixture was

30–33%. At this percentage of chitosan,

both the polymers probably reacted max-

imum to form an insoluble complex. The

percentage of polymer at this stage in the

supernatant would be minimum, which in

turn would develop lowest viscosity. The

observed higher viscosity at the latter stage

might be due to the presence of unreacted

chitosan in the supernatant.

Copyright � 2012 WILEY-VCH Verlag GmbH & Co. KGaA

Effect of Variation of pH

The effect of variation of pH (2.0–5.5) on %

yield was plotted in Figure 2(a), which was

plotted as the coacervate yield (%)

against pH. The coacervate yield increased

initially with the increase of pH, reached

maximum at pH range 2.5–3.5 and then

again decreased. This implied that the

coacervation between the two polymers

was highest at this pH range. The explana-

tion for this was similar to that of given

earlier.

Change in relative viscosity of the

supernatant with variation in pH in chit-

osan–SCMC mixture was shown in

Figure 2(b). Viscosity was found to

decrease initially, reaching a minimum

value, and after that it increased. In

the pH range 2.5–3.5, the minimum viscos-

ity was observed implying that this pH

range is the optimum pH range for max-

imum complexation between the two poly-

mers.

Effect of Variation of Amount of

Surfactant and Polymer Concentration on

Size of the Microparticles

The formation and particle size of each

microparticle depends on the size of the

dispersed droplet, which is determined by

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Macromol. Symp. 2012, 313-314, 69–7874

the surfactant (tween 80) used and the

emulsifying conditions. For the system of

SCMC-chitosan, surfactant tween-80 had

important role in stabilizing the micropar-

ticles formed in sunflower oil. A matrix gel

like product was formed if surfactant was

not added. But different sizes of micro-

particles were formed on addition of

varying amount of surfactant. SEM photo-

graphs of the microparticles were shown in

Figure 3(a–d). With the increase of amount

of tween-80 the sizes of the microparticles

decreased as shown in Figure 3(a–c). At

higher concentration of surfactant, the

aqueous phase is easily dispersed into finer

droplets, owing to the higher activity of the

surfactant, which would result in a lower

free energy of the system, and lead to a

smaller particle size.

Water Uptake Study

The swelling of microparticles is found to

be pH dependent. The water uptake of

microparticles was plotted against time of

Figure 3.

Scanning electron micrographs of microparticles prepar

polymer¼ 0.645 g (b) tween 80¼ 0.7751 g/g of polyme

polymer, total polymer¼ 0.645 g (d) tween 80¼ 1.162 g/

Copyright � 2012 WILEY-VCH Verlag GmbH & Co. KGaA

immersion in water (Figure 4). Water

uptake was more at pH 7.4 compared to

that at lower pH 1.2 (0.1 M HCl). Micro-

particles formed by the complexation

between chitosan and SCMC became more

stable probably at lower pH. The swelling

ability of the microparticles under an acid

environment was weakened. Zhang et al

reported similar findings and explained the

phenomenon in that, in a low pH condition,

the amino groups from chitosan were

protonated and the electrostatic interaction

of carboxyl groups of SCMC with the amino

groups of chitosan was strengthened,

resulting in a dense structure.[20] Another

explanation for higher swelling at

higher pH may be due to the tendency to

decomplexation between chitosan and

SCMC. Another similar type of findings

were reported by Liu et al.[21] during

studying the swelling behaviour of gela-

tin-DNA semi-interpenetrating polymer

network at different pH. Microparticles

with higher crosslinking showed lesser

ed by using (a) tween 80¼ 0.38 g/g of polymer, total

r, total polymer¼ 0.645 g (c) tween 80¼ 1.162 g/g of

g of polymer, total polymer¼ 1.29 g.

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Figure 4.

Effect of variation crosslinker amount and pH on

water uptake a: polymer¼ 1.29 g; crosslinker¼4.375mmol/g of polymer; pH¼ 7.4, b: polymer¼1.29 g; crosslinker¼ 4.375mmol/g of polymer;

pH¼ 1.2, c: polymer¼ 1.29; crosslinker¼ 17.50mmol/g

of polymer; pH¼ 7.4, d: polymer¼ 1.29 g; crosslinker¼17.50mmol/g of polymer; pH¼ 1.2.

Table 1.Effect of variation of isoniazid concentration and imme

Concentration ofglutaraldehyde(mmol)/g of polymer

Concentration ofisoniazid g/100ml

4.375 0.51.03.05.07.010.020.0

10.50 0.51.03.05.07.010.020.0

17.50 0.51.03.05.07.010.020.0

17.50 5.0

4.375 20.010.50 20.017.50 20.0

Copyright � 2012 WILEY-VCH Verlag GmbH & Co. KGaA

Macromol. Symp. 2012, 313-314, 69–78 75

water uptake than the microparticles with

low crosslinking. This was due to the

formation of more compact wall[22] caused

by crosslinking.

Effect of Variation of Drug and Crosslinker

Concentration and Immersion Time on

Loading Efficiency

The effects of variation of concentration of

isoniazid and immersion time of micro-

particles on loading efficiency were studied

and are shown in Table 1.

At a fixed immersion time, the loading

efficiency was found to increase with the

increase in the concentration of isoniazid.

An increase in loading efficiency was also

observed as immersion time increased.

Again, higher the amount of crosslinker

rsion time on loading efficiency.

Time ofimmersion (h)

Loadingefficiency (%)

2.0 4.95� 0.0111.02� 0.1323.22� 0.1235.0� 0.1746.0� 0.2154.0� 0.6362.5� 0.55

2.0 3.45� 0.0110.02� 0.1120.0� 0.1633.01� 0.2943.51� 0.3550.33� 0.3958.50� 0.67

2.0 1.02� 0.012.62� 0.1212.52� 0.3222.0� 0.4732.48� 0.5841.11� 0.5951.50� 0.73

0.5 4.05� 0.381.0 15.0� 0.222.0 22.0� 0.424.0 28.0� 0.516.0 33.45� 0.548.0 38.12� 0.4317.0 49.0� 0.4628.0 57.0� 0.6548.0 58.50� 0.4460.0 69.8� 0.4660.0 69.0� 0.5260.0 68.5� 0.40

, Weinheim www.ms-journal.de

Macromol. Symp. 2012, 313-314, 69–7876

in the microparticles, the lower was the

loading efficiency. The increase in loading

efficiency was due to the more diffusion of

isoniazid into the microparticles. The

decrease in loading efficiency might be

attributed to the formation of more com-

pact wall due to crosslinking that led to

decrease in diffusion rate of isoniazid.

Again, at a fixed isoniazid concentration,

the loading efficiency increased with time of

immersion up to a certain time and after

that it remained constant. But, high and

low crosslinked microparticles showed

more or less similar loading efficiency when

immersed in similar concentration of iso-

niazid solution for a longer period. Longer

immersion time allowed the microparticles

to become saturate with isoniazid solution.

Effect of Variation of Cross-Linker on

Release Rate of Isoniazid

The effect of variation of crosslinker

concentration (4.375–17.50 mmol/g of poly-

mer) on release rate at pH 1.2 and 7.4 is

shown in Figure 5. Microparticles having

approximately similar loading were chosen

for the study of the release rate at

different pH. The release rate of isoniazid

was found to decrease with the increase in

the amount of crosslinker in the micro-

particles. In all the cases, the release was

fast initially, reaching maximum and

levelled off finally. The compact micro-

Figure 5.

Effect of variation of crosslinker concentration and pH

on release profile a: polymer¼ 1.29 g; crosslinker¼4.375mmol/g of polymer; pH¼ 7.4, b: polymer¼1.29 g; crosslinker¼ 4.375mmol/g of polymer; pH¼ 1.2,

c: polymer¼ 1.29; crosslinker¼ 17.50mmol/g of

polymer; pH¼ 7.4, d: polymer¼ 1.29 g; crosslinker¼17.50mmol/g of polymer; pH¼ 1.2.

Copyright � 2012 WILEY-VCH Verlag GmbH & Co. KGaA

particle wall was responsible for the

decrease in release rate as explained ear-

lier.

Drug release was dependent on pH. The

percentage of isoniazid release at lower pH

(pH¼ 1.2) was less compared to that of

at higher pH (pH¼ 7.4). This pH depen-

dent release is supported by the pH

dependent swelling of the chitosan-SCMC

complex. The lower and higher release rate

in lower and higher pH respectively might

be explained by considering the tendency of

complexation and decomplexation between

chitosan and SCMC as discussed earlier.

Fourier Transform Infrared (FTIR) Study

The spectrum (Figure 6) of SCMC showed

absorption bands at 3364 cm�1, 2942 cm�1,

1627 cm�1, 1422 cm�1, 1063 cm�1 which

were due to O�H stretching vibration,

CH3 symmetric and CH2 assymetric vibra-

tion, C�O stretching band for cellulose,

CH3 and CH2 bending vibration and strong

C�O stretching band for ethers. The

spectrum of chitosan showed a strong

absorption band at 1635.33 cm�1 assigned

to NH bending. The other notable peaks

appeared at 3435, 2920, 1425 and 1384,

1330, 1170, 1075, and 1030 cm�1, were due

to O�H and N�H stretching vibration,

CH3 symmetric and CH2 asymmetric vibra-

tion, CH3 and CH2 bending vibration,

vibration of C�N group, C�O�C asym-

metric vibration, C�O(�C�OH�) vibra-

tion, and C�O(�CH2 �OH�) vibration,

respectively. A new absorption band peak

at 1742.83 cm�1 was observed in the

chitosan-SCMC complex which was caused

by the electrostatic interaction between

the �COOH groups of CMC and �NH2

groups of chitosan.[20] Another new and

weak absorption band around 1528 cm�1

assigned to �NHþ3 groups is observed in the

polyelectrolyte complex. Thus �NHþ3

groups in chitosan participate in binding

with SCMC probably through its �COO�

groups.[23] In the spectrum of isoniazid

(Figure 6d), the carbonyl absorption

(amide I band) appeared at 1664 cm�1.

The amide II band that occurred at

1555.90 cm�1 was due to N�H bending of

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Figure 6.

FTIR spectra of a) SCMC b) Chitosan c) Chitosan-SCMC complex d) isoniazid e) microparticles without isoniazid

loading f) isoniazid loaded microparticles.

Figure 7.

X-ray diffractograms of (a) isoniazid loaded micro-

spheres (b) microspheres without isoniazid (c) iso-

niazid.

Macromol. Symp. 2012, 313-314, 69–78 77

the secondary amide group. Moreover, in

the spectrum of isoniazid, multiple bands

appeared between 1400 cm�1 to 668 cm�1.

Appearance of characteristic bands of

isoniazid in the isoniazid loaded micro-

Copyright � 2012 WILEY-VCH Verlag GmbH & Co. KGaA

particles suggested the successful loading of

isoniazid in the microparticles (Figure 6f).

X-ray Diffraction (XRD) Study

X-ray diffractograms of chitosan-SCMC

microparticles, isoniazid loaded micropar-

ticles and isoniazid were studied (Figure 7).

Isoniazid showed multiple sharp peaks

at 2u varying from 12 to 608 which were

due to the crystalline nature of isoniazid.

Appearance of some of these multiple

sharp peaks in the diffractograms of

isoniazid loaded microparticles indicated

development of some crystallinity due to

the encapsulation of isoniazid.

Conclusion

The optimum conditions for maximum

complexation between chitosan and

SCMC occurred at chitosan: SCMC: ratio

of 1.0:2.33 and pH range of 2.5–3.5.

The size of the microparticles can be

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Macromol. Symp. 2012, 313-314, 69–7878

varied by varying surfactant and polymer

concentration. Isoniazid concentration gov-

erned the absorption of isoniazid into the

microparticles. The swelling of the micro-

particles was dependent on crosslinker

and pH. The release of isoniazid was more

at pH 7.4 compared to lower pH of 1.2.

Isoniazid release was also controlled by

crosslinking the polymer with glutarade-

hyde. FTIR study indicated the polyelec-

trolyte complexation between chitosan-

SCMC and loading of isoniazid into the

microparticles. XRD studies showed

that isoniazid was dispersed in the micro-

particles.

Acknowledgements: The research has beensponsored by the University Grants Commissionunder the UGC Dr. D.S. Kothari Post Doctoralfellowship Scheme. The author (ND) is gratefulto UGC for financial assistance.

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