FORMULATION AND EVALUATION OF TIME CONTROLLED DRUG DELIVERY SYSTEM...

INTERNATIONAL JOURNAL OF RESEARCH ARTICLE PHARMACEUTICAL INNOVATIONS ISSN 2249-1031

1 | P a g e Volume 2, Issue 3, May₋ June 2012 http://www.ijpi.org

FORMULATION AND EVALUATION OF TIME CONTROLLED

DRUG DELIVERY SYSTEM OF MONTELUKAST SODIUM

Bailpattar Padmaxi *1 karwa Preeti 1 Patel Kirtan 1 Mondal Md. Sahidullah 2

Pasha Mohamed Irshad 2

1 Nargund college of Pharmacy, Bangalore- 560085, Karnataka

2MMU College of Pharmacy, Ramanagaram- 562159, Karnataka

Abstract:

Aim of the present work was to formulate and evaluate an oral, time controlled drug delivery

system of Montelukast sodium, based on chronopharmaceutical approach for the treatment of

nocturnal asthma. It consisting of a core surrounded by coat layer of different ratios of

swellable erodible hydrophilic layer Sodium Alginate and HPMC K4M. The prepared

pulsatile tablets were evaluated for the drug content, thickness and in vitro release profile. In

vitro release profiles of 6 to 9 hours studies were found to have minimum or no drug release

and at the end of 5 hours immediate release was observed. It was observed that lag time

increased with increased concentration of HPMC K4M due to no seepage of dissolution fluid

into the core. The lag time decreased with the increased concentration of Sodium Alginate

resulted in faster and burst release of drug from a core tablets. Higher concentration of

HPMC alone was able to maintain the lag time up to 6 h and Sodium alginate for 1 h. The

programmable time controlled release has been achieved from a press-coated tablet over a

period of 5 hr and burst release was obtained after a lag time, which was consistent with the

demands of chronotherapeutic drug delivery.

Key words: Time controlled drug delivery; Chronotherapeutics; Montelukast sodium, HPMC

K4M; Sodium Alginate

INTRODUCTION:

For many decades, treatment of an

acute disease or a chronic illness has been

mostly accomplished by delivering drugs

using various pharmaceutical dosage

forms, including tablets, capsules, pills,

suppositories, creams, ointments, liquids,

aerosols, and injectables as carriers.

Amongst various routes of drug delivery,

oral route is perhaps the most preferred to

the patient and the clinician alike. These

traditional pharmaceutical products are

still commonly seen today in the

prescription and over-the-counter drug

marketplace. To achieve and maintain the

*Corresponding Author

Bailpattar Padmaxi



drug concentration in the body within the

therapeutic range required for a

medication, it is often necessary to take

this type of drug delivery system several

times a day. [1]

To introduce the concept of

chronopharmaceutics, it is important to

define the concepts of chronobiology and

pharmaceutics. The term "chrono"

basically refers to the observation that

every metabolic event undergoes rhythmic

changes in time. Chronobiology is the

study of biological rhythms and their

mechanisms. Pharmaceutics is an area of

biomedical and pharmaceutical sciences

that deals with the design and evaluation

of pharmaceutical dosage forms (or drug

delivery systems) to assure their safety,

effectiveness, quality and reliability.

The potential benefits of

chronotherapeutics have been

demonstrated in the management of a

number of diseases. In particular there is a

great deal of interest if how chronotherapy

can particularly benefit patients suffering

from allergic rhinitis, rheumatoid arthritis

and related disorders, asthma, cancer,

cardiovascular diseases, and peptic ulcer

disease.[2]

A circadian rhythm is an

endogenously driven roughly 24-hour

cycle in biochemical, physiological, or

behavioral processes. Circadian rhythms

have been widely observed

in plants, animals, fungi and cyanobacteria

. The term "circadian" comes from

the Latin circa, meaning "around",

and diem or dies, meaning "day". The

formal study of biological temporal

rhythms such as daily, tidal, weekly,

seasonal, and annual rhythms is

called chronobiology. Biological rhythms

are defined by a number of characteristics.

Oscillations of shorter duration are termed

‘‘ultradian’’ (more than one cycle per 24

h). Oscillations that are longer than 24 h

are ‘‘infradian’’ (less than one cycle per 24

h) rhythms. Ultradian, circadian, and

infradian rhythms coexist at all levels of

biologic organization. [3]

Several physiological processes

in humans vary in a rhythmic manner, in

synchrony with the internal biological

clock. It represents the overview of most

serious diseases displaying significant

daily variations. Many of circadian

dependent diseases display acute

symptoms in early morning hours or in the

morning at awakening.

Diseases, such as asthmas,

hypertension, peptic ulcer, arthritis, etc,

follow the body's circadian rhythm. For

example, osteoarthritis worsens during the

day and is most bothersome in the

evenings but for people with rheumatoid

arthritis, the pain usually peaks in the

morning and decreases as the day

progresses. Cardiovascular diseases such

as hypertension and angina, and chest pain,

also follow a definite circadian rhythm.

Epidemiologic studies have documented

the heightened morning-time risk of

angina, myocardial infarction, and stroke.

[4]

Through a number of clinical

trials and epidemiological studies, it has

become evident that the levels of diseases

activity of a number of clinical disorders

have a pattern associated with the body’s

http://en.wikipedia.org/wiki/Plant

http://en.wikipedia.org/wiki/Animal

http://en.wikipedia.org/wiki/Fungi

http://en.wikipedia.org/wiki/Cyanobacteria



http://en.wikipedia.org/wiki/Latin

http://en.wikipedia.org/wiki/Circa

http://en.wikipedia.org/wiki/Tidal

http://en.wikipedia.org/wiki/Chronobiology



inherent clock set according to circadian

rhythms.

Asthma is a chronic

inflammatory disease of the airways,

characterized by hyper responsiveness to a

variety of stimuli. [5]

The role of circadian

rhythms in the pathogenesis and treatment

of asthma indicates that airway resistance

increases progressively at night in

asthmatic patients. Circadian changes are

seen in normal lung function, which

reaches a low point in the early morning

hours. The worsening of asthma at night,

commonly referred to as nocturnal asthma

(NA).A drug delivery system administered

at bedtime but releasing drug during

morning hours would be ideal in this case.

Nocturnal asthma is a variable

exacerbation of the underlying asthma

condition associated with increases in

symptoms, need for medication, airway

responsiveness, and/or worsening of lung

function. Approximately two-thirds of

asthmatics suffer from nighttime

symptoms. Lung function (e.g., peak

expiratory flow rate or FEV1) is usually

highest at 4 PM and lowest at 4 AM. Many

circadian-dependent factors appear to

contribute to the worsening of nocturnal

asthmatic symptoms. For example, cortisol

(an anti inflammatory substance) levels

were highest at the time of awakening and

lowest in the middle of the night, and

histamine (a mediator of

bronchoconstriction) concentrations

peaked at a level that coincided with the

greatest degree of bronchoconstriction at

4:00 am. [6]

Based on these findings drug

delivery and therapy should be modified to

achieve an effective drug level at the

required time. This can be achieved by

adapting a time controlled or pulsatile drug

delivery system of a suitable drug.

Consequently, the administration of a drug

formulated in such a delivery system, i.e.

taken at bedtime with a programmed start

of drug release in early morning hours,

could offer a more effective therapy than a

typical controlled release drug delivery

system, provided that the most appropriate

drugs are administrated. Pulsatile drug

delivery system is the one type of drug

delivery system, where the delivery device

is capable of releasing drug after

predetermined time-delay (i.e. lag time)

known as pulsatile drug delivery system

(PDDS).[7]

PDDS are gaining lot of interest

and attention these days. These systems

have a peculiar mechanism of delivering

the drug rapidly and completely after a

"lag time," i.e., a period of "no drug

release." Oral pulsatile administration

could be useful for the treatment of certain

diseases, such as asthma, gastric ulcer,

hypertension, ischemic heart disease,

arthritis, etc., which exhibit circadian

rhythms. Pulsatile drug delivery denotes

the capability of a controlled release

preparation to deliver the drug at varying

rates from very low to high over a

desirable time. PDDS is classified into

various systems like enteric coated system,

layered system, sigmoid system, press

coated system, single unit system and

multiple unit system. [8]

Press coated tablets (PCTs)

gained wide interest ‘claiming some



advantages over regular and (pan-) coated

tablets, such as to protect hygroscopic,

light-sensitive or oxygen-labile drugs from

environmental-atmospheric ill effects or

decomposition of acid-labile drugs by

gastric fluids; to separate incompatible

drugs from each other; to achieve a

sustained release in that the drug in the

core is embedded in waxes or fats

constituting a depot; to protect the gastric

mucosa from irritation by certain drugs by

using enteric coating material in the outer

press-coating granules; or to achieve

intermittent release by incorporating one

portion of drug in the core and the other in

the coat, separated by a film-coat or a

second press-coat. However, common

drawbacks of the press-coating technique

are the multistep processes involved, and

the requirement for reliable and

reproducible central positioning of the core

tablet within press-coated tablet (PCT), a

major challenge for large scale industrial

manufacturing. The lag time of drug

release from PCTs depends upon the

thickness and the composition of the

barrier layer. Generally speaking, the

thicker the barrier layer, the longer the lag

time. The composition of the barrier layer

controls the mechanism of effecting a lag

time. Besides capsule based pulsatile

release systems, formulations, such as

Pulsicap have also been developed. These

systems consist of a water-impermeable or

semi-impermeable capsule half with the

drug formulation contained within the

capsule and sealed by means of a hydrogel

polymer plug. Contact of the dissolution

media or gastrointestinal fluids with the

barrier or the plug results to its removal or

ejection followed by the rapid release of

the drug. [9]

The aim of the present

investigation was to develop and evaluate

an alternative, simple, orally applicable

one pulse drug delivery system based on a

press-coated tablet preparation. It

consisting of a rapidly disintegrating core

tablet press coated by a barrier layer

consisting of varying concentrations of

Sodium Alginate and Hydroxypropyl

methyl cellulose (HPMC K4M). HPMC

and Sodium alginate are used as a rate

controlling polymer. Combination of these

polymers were able to achieve various lag

time.

MATERIALS AND METHOD:

Materials:

Montelukast Sodium - model drug, was

obtained from Micro lab Ltd, Bangalore,

India. Croscarmellose sodium (Ac-Di-Sol),

HPMC K4M (Methocel), Sodium alginate

were gifted from Alembic Pvt. Ltd,

Vadodara, India. Magnesium stearate,

Lactose Monohydrate and Sodium Lauryl

Sulphate (SLS) were gifted from S.D. Fine

chem. Ltd, Mumbai, India. All the other

chemicals and reagents were either

analytical or pharmaceutical grades.

Preformulation Study:

Bulk density, tapped density, Hausner’s

ratio, carr’s index and angle of repose was

perform for polymeric blends.

Drug excipient interaction:

Compatibility of the Drug with the

excipients is determined by subjecting the

physical mixture of the drug and the

polymers of the main formulation to

infrared absorption spectral analysis



(FTIR). Any changes in chemical

composition of the drug after combining it

with the polymers were investigated with

I.R. spectral analysis.

Procedure: Weighed amount of drug (3

mg) was mixed with 100mg of potassium

bromide (dried at 40-50oC). The mixture

was taken and compressed under 10-ton

pressure in a hydraulic press to form a

transparent pellet. The pellet was scanned

by IR spectrophotometer. Similar

procedure is followed for all relevant

excipients used.

Tablet manufacturing method:

Formulation of core tablet by direct

compression method: [10]

The inner core tablets were prepared by

using direct compression method. The

powder mixtures of Montelukast sodium,

Lactose (lactochem), croscarmellose

sodium (Ac-Di-Sol) ingredients were dry

blended for 20 min. followed by addition

of Magnesium Stearate. The mixtures were

then further blended for 10 min., 100mg of

resultant powder blend was manually

compressed using tablet pushing machine

(Rimek mini press-1) with a 6.3 mm punch

and die to obtain the core tablet. Formula

for formulation of the core tablet was

shown in the Table 1.

Formulation of mixed blend for barrier

layer

The various formulation Compositions

containing sodium alginate and HPMC

K4M were prepared i.e. formulation from

F1 to F8 different compositions were

weighed and dry blended at about 10 min.

and used as press-coating material to

prepare press-coated pulsatile tablets

respectively by direct compression

method.

Precompression including (bulk density,

tapped density, total porosity, Hausner’s

ratio compressibility index, angle of

repose) were done for both core powder

and mixed blend of the barrier layer.

Formula for formulation of the barrier

layer (200 mg) coating was shown in the

Table 2.

Development of Press-coated tablets:

The core tablets were press-coated with

200 mg of mixed Blend. 100 mg of barrier

layer material was weighed and transferred

into a 9.54 mm die then the core tablet was

placed manually at the center. The

remaining 100 mg of the barrier layer

material was added into the die, so that the

core tablet get covered by the barrier layer

completely and compressed by tablet

punching machine (Rimek mini press-1).

The total weight of the tablet would be 300

mg. Formula for formulation of press-

tablets (300 mg) was shown in the Table 3.

Evaluation of press coated tablets: [11]

Core and press-coated tablets were

evaluated for weight variation, thickness,

hardness, friability test, content uniformity

test. These parameters are known as post

compression parameters.

Thickness of the tablets was determined by

Vernier caliper. Pzifer Monsanto tester

was used to determine the hardness of the

tablets. 5 tablets were taken for each test.

Friability was determined by placing 10

tablets in Roche Friabilator, it denotes the

mechanical strength of the tablets. For

determining the content uniformity test, 10



tablets were taken and crushed, weight

equivalent to 100 mg was taken and

dissolved in SLS. Further dilutions were

made to get the concentration of 10 µg/ml.

the solution was analyzed for Montelukast

content by UV-Spectrophotometer at 345.5

nm by using SLS as a blank.

In vitro release study of core tablets [12]

In vitro release studies of core tablets were

carried out in USP Type II (Paddle Type)

apparatus by using 0.5% of SLS in water

as a dissolution media. Rotated at 50 rpm

and temperature maintained at 37 ± 0.5˚C.

Sample was withdrawn periodically at the

interval of 5 mins and analyzed by UV-

spectrophotometer at 345.5 nm.

In vitro release study of Press-coated

tablets

In vitro dissolution studies were carried

out in USP Type II (Paddle Type)

apparatus. All the conditions were

maintained same as mentioned above.

Sample was withdrawn periodically at the

interval of 1 h until coat ruptures then

samples were withdrawn in ½ h intervals

and analysed by UV-spectrophotometer at

345.5 nm using 0.5% of SLS as a blank.

Swelling index: [13]

Swelling effect on lag time and release

behavior was observed. A known weight

of a tablet was placed in 0.5% of SLS and

allowed to swell for the required period of

time at 37ºC ± 0.5ºC in the dissolution

apparatus (Dissolution Tester USP 2). A

tablet was periodically removed and

blotted with filter paper; then their change

in weight (after correcting for drug loss)

was measured until attainment of

equilibrium. The swelling ratio (SR) was

then calculated using the following

formula:

WF - WI ×100

SR=

WI

Where

SR= swelling ratio,

WF = weight of the tablet after swelling,

WI= initial weight of the tablet.

RESULT AND DISCUSSION:

An absorption maximum was determined

by scanning different concentration of

solution of drug Montelukast sodium. It

was found to be 345.5 nm and method

obeys Beer’s law in concentration range 5

to 25µg/ml, r2 was found to be 0.0097.

Preformulation test of polymeric

blends:

Bulk density, tapped density, Hausner’s

ratio and carr’s index given in the Table 4.

The angle of repose (θ) for all the

formulation blends of Coated was below

30º indicating good flow property.

IR spectra of optimized

formulation F7 (25:100) was compared

with IR spectra of the pure drug samples.

No change in the peak occurred with

demonstrated no incompatibility with the

excipients used. FTIR spectrum was

shown in the figure 1 & 2.

Evaluation of press-coated tablets:

Post compression parameters like weight

variation, thickness, hardness, friability are

given in table No 5. Weight variation

(n=20) was found to be 298.89 ± 1.007 to



300.02 ± 1.741. Thickness (n=5) ranging

from 5.26 ± 0.342 to 5.33 ± 0.031 mm.

Hardness (n=5) was ranging from 5-6

kg/cm2. Friability of press-coated tablets

was found to be 0.177 to 0.289 %,

indicating good mechanical strength. Drug

content of coated tablets were found to be

98.56 ± 0.300 to 99.81 ± 0.312 %

indicating uniform distribution of drug.

Result was shown in the Table 5.

In vitro dissolution of core tablet:

The core tablets shows 70% of drug

release within 5 mins followed by the

maximum release in 15 mins upon contact

with dissolution media.

In vitro dissolution of coated tablets:

From visual observation of in vitro

dissolution studies it become apparent that

upon contact of the tablet with the liquid,

the outer layer consisting of the

hydrophilic polymers, starts to absorb

liquid. As a consequence the polymer

swells and shortly after an expansion of

the layer was noticed. As the time passes

the swelling and the expansion of the top

layer increases creating a considerable

barrier which may delay to some extent the

contact of the bulk liquid with the surface

of the Core drug tablet. The swelling

process of the outer barrier layer could act

as a disintegrating force, which facilitates

firstly the destabilization of the barrier

layer itself. The balance between these two

forces disintegration (sodium alginate) and

swelling (HPMC K4M) controls the

behavior of the outer barrier layer (i.e. the

erosion process of the polymer) and

consequently the performance of the

system. Finally depending on the

properties of each polymer i.e. Sodium

alginate and HPMC K4M, the outer barrier

layer is removed and as result the

dissolution of the Core drug tablet increase

sharply due to increased access of liquid

into the Core of the tablet. HPMC K4M

showed maximum swelling which lasts

longer but the erosion appeared to be

greater after maximum swelling for

Sodium alginate. Thus the greatest bulk

swelling is achieved with both Sodium

alginate and HPMC K4M and after lag

time erosion appeared due to Sodium

alginate and drug is released from Core.

During the course of studies it was

observed that F7 (25:100) showed a lag

time of 5 h and immediate release of drug

was found. Formulation F7 selected as an

optimized formulation as it was meeting

chronotherapeutics system for the

treatment of asthma. Release study of the

prepared formulations was shown in the

Figure 3-4.

Swelling index:

The optimized formulation F 7 were

subjected for the determination of bulk

volume swelling reflecting extent of liquid

uptake and the loss of weight reflecting

erosion on the tablet. Visual observation

indicated that both polymers swelled and

created a viscous gel at the top layer

surface when they are exposed to the

dissolution medium. During the coarse of

the study, a maximum swelling achieved

followed by erosion of the hydrophilic

polymer layer. (Fig- 5)

The barrier layer exhibited slower

liquid uptake and the maximum uptake

swelling (80 %) was achieved at 5 hr.

These indicate that in Montelukast sodium

tablets, drug molecule are released by

diffusion out of the gelatinous layer once



the polymer outer layer had been fully

hydrated and the liquid molecules come in

contact with the Core tablet. As time

passes, the erosion of the polymer and

progress of the dissolution of the drug

occur almost simultaneously and

termination of drug release coincides

approximately with erosion of the outer

layer.

CONCLUSION:

The novel Time controlled Chronotropic

drug delivery system for oral use was

successfully developed and evaluated. The

formulation consisted of a core tablet

containing a drug Montelukast sodium and

outer layer of combination of swellable,

erodible hydrophilic polymer. The present

study demonstrated that the press-coated

tablets of Montelukast sodium was

successfully developed with desired lag

time of 5 hrs by using combination of

Sodium Alginate and HPMC K4M. It was

concluded that Formulation F7 (25:100)

was the ideal formulation with lag time of

5 hrs followed by burst release of drug and

also meeting all specifications of pre-

compression and post compression

parameters and stability studies.

ACKNOWLEDGEMENT:

We are thankful to wish to Micro lab Ltd,

Bangalore, India for providing the gift

sample of Montelukast sodium. We are

also thankful to the Nargund and M.M.U

college of Pharmacy for providing all

necessary facilities.

REFERENCES:

1. Jain NK. Controlled and novel

drug delivery. 1st ed. New Delhi:

CBS Publishers; 2002.

2. Jha N, Bapat S. Chronobiology and

chronotherapeutics: A review.

Kathmandu university Med. J.

2004; 2(8): 384-388.

3. Sarasija S, Stutie P.

Chronotherapeutics: Emerging role

of biorhythms in optimizing drug

therapy. Indian J. Pharm. Sci.

March-April 2005; 67(2): 135-140.

4. Sangita V. Timing is everything.

Nov. 2009;

http://www.pharmaquality.com/Fea

ture.7ahtm.

5. Smolensky M, Lemmer B,

Reinberg A. Chronobiology and

chronotherapy of allergic rhitis and

bronchial asthma. Advance drug

del. Reviews. 2007; 852-882

6. Gwen SS. Nocturnal asthma:

mechanisms and management. The

Mount Sinai J. Medicine.May

2002; 69(3): 140-147.

7. Reddy J, Jyosthna M, Saleem T,

Chetty C. Pulsatile drug delivery

system: A review. J. Pharm. Sci.

and Res. 2009; 1(4): 109-115.

8. Gothaskar AV, Joshi AM, Joshi

NH. Pulsatile drug delivery

system: A review. Drug

Del.Tech.June 2004; 4(5).

9. Sajan J, Cinu TA, Chacko AJ, Litty

J, Jaseeda T. Chronotherapeutics

and Chronotherapeutics drug

delivery system: A Review.

Tropical J. Pharmaceutical Res.

Oct. 2009; 8(5): 467-475.



10. Janugade BU, Patil SS, Patil SV,

Lade PD. Formulation and

evaluation of press-coated

Montelukast sodium tablet for

pulsatile drug delivery system. Int.

J. chem. and Tech. Res. July-

sep.2009;1(3): 690-691.

11. Verma S, Valecha V, Singh SK,

Syan N, Mathur P. Development

and evaluation of Montelukast

sodium colon targeted matrix

tablets based on pulsatile approach

for nocturnal asthma.Int.J.

Pharmaceutical sci. Review and

Res. May-June 2011; 8(1): 129-

137.

12. Government of India Ministry of

Health & Family Welfare. Indian

Pharmacopoeia. Delhi:Controller

of Publications. 2007; 3: 1689-

1690.

13. Patel GC, Patel MM. A

comparative in vitro evaluation of

enteropolymers for Pulsatile drug

delivery system. Acta

Pharmaceutica Sci. 2009; 51: 243-

250.

Table 1: Formulation of the core tablet Table 2: Formulation of the barrier layer (200 mg)

SN Sodium alginate (mg)

HPMC K4M (mg)

Lactose (mg)

F1 40 60 100

F2 50 50 100

F3 50 100 50

F4 75 75 50

F5 75 100 25

F6 100 75 25

F7 25 100 75

F8 100 100 0

SN Ingredients Quantity

(mg)

1 Montelukast

Sodium (MKS)

10.4

2 Lactose 82.6

3 Croscarmellose

sodium

10

4 Magnesium stearate 2

Total weight 100 mg



Table 3: Formulation of press-coated Table 4: Precompression parameters of the polymeric blend

Tablets (300 mg)

Table 5: Post compression parameters of press-coated tablets

Batch Thickness

(mm)

Hardness

(kg/cm2)

Wt. variation Friability

(%)

Drug content

(%)

F1 5.26±0.342 5-6 299.45±2.811 0.231 98.90±0.501

F2 5.33±0.031 5-6 300.01±0.910 0.144 99.81±0.312

F3 5.30±0.024 5-6 300.02±1.741 0.088 99.42±0.402

F4 5.31±0.003 5-6 299.44±1.140 0.289 98.56±0.300

F5 5.29±0.257 5-6 298.89±2.007 0.216 97.32±0.210

F6 5.29±0.269 5-6 300.01±1.119 0.192 98.78±0.251

F7 5.30±0.031 5-6 299.60±1.818 0.177 99.40±0.310

F8 5.31±0.027 5-6 299.55±0.973 0.176 99.12±0.411

BL : CORE

(200:100)

S: H

(RATIO)

F1 40:60

F2 50:50

F3 50:100

F4 75:75

F5 75:100

F6 100:75

F7 25:100

F8 100:100

Batch Bulk

density

(w/v)

Tapped

density

(w/v)

Hausner’s

ratio

Carr’s

index

Angle

of

repose

(θ)

F1 0.384 0.439 1.14 12.53 22.75

F2 0.416 0.480 1.15 13.33 24.14

F3 0.395 0.452 1.14 12.61 25.31

F4 0.367 0.390 1.06 5.90 25.39

F5 0.361 0.409 1.13 11.74 28.11

F6 0.352 0.397 1.13 11.34 26.14

F7 0.413 0.443 1.07 6.77 25.34

F8 0.414 0.477 1.15 6.21 24.34



Fig 1: FTIR spectrum of Montelukast sodium

Fig 2: FTIR spectra of physical mixture of optimized formulation F7

Figure 3: Percentage drug release of F1, F2 F3and F4

-20

0

20

40

60

80

100

120

0 2 4 6 8 10

C

P

R

time(h)

% drug release with time

F1

F2

F3

F4



Figure 4: Percentage drug release of F5, F6, F7 and F8

Figure 5: swelling index of optimized formulation F7

-20

0

20

40

60

80

100

120

0 2 4 6 8 10

C

R

P

time(h)

% drug release with time

F5

F6

F7

F8

0

20

40

60

80

100

0 2 4 6 8

%

w

e

i

g

h

t

g

a

i

n

time (h)

swelling index

F7

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