Vous êtes sur la page 1sur 12

Indo American Journal of Pharmaceutical Research, 2014

ISSN NO: 2231-6876

FORMULATION AND IN VITRO EVALUATION OF CONTROLLED RELEASE MATRIX


TABLETS OF FLURBIPROFEN
R.Prashanthi1, P.Naga Haritha*1, E.Hima Bindu1, P.Sunil Kumar Chaitanya2, Akram Khan1.
1

Department of Pharmaceutics, St.Pauls college of Pharmacy, Turkayamjal, Hayathnagar, Rangareddy, Telangana 501510, India.
Department of Pharmaceutical Analysis & Quality Assurance, St.Pauls college of Pharmacy, Turkayamjal, Hayathnagar,
Rangareddy, Telangana 501510, India.
2

ARTICLE INFO
Article history
Received 05/12/2014
Available online
16/12/2014

Keywords
Flurbiprofen ,
HPMC K100 M,
Sodium CMC,
Xanthan Gum,
Guar Gum,
Controlled Release Tablets.

ABSTRACT
Oral drug delivery has been known for decades as the most widely utilized route of
administration among all the routes that have been explored for the systemic delivery of drugs
via various pharmaceutical products of different dosage forms. Flurbiprofen is having
biological half life 4.7 hr to 5.7 hr, thereby increasing dosing frequency. In order to decrease
its dosing frequency controlled release matrix tablets were developed. In the present work, an
attempt has been made to develop controlled release matrix tablets of Flurbiprofen by
selecting different polymers like HPMC K100, Sodium Carboxy Methyl Cellulose, Xanthan
gum and Guar gum. All the formulations were prepared by direct compression method using
12mm punch on 8 station rotary tablet punching machine. The blend of all the formulations
shown good flow properties such as angle of repose, bulk density, tapped density. The
prepared tablets were shown good post compression parameters and they passed all the
quality control evaluation parameters as per I.P limits. Among all the formulations F12
formulation that is with Guar Gum showed maximum percentage drug release i.e., 99.18 % in
12 hours. Hence it is considered as optimized formulation. The retardation in the release of
the drug from optimized formulation is may be due to the increase in the concentration of the
polymer.

Copy right 2014 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical
Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

www.iajpr.com

Page

Please cite this article in press as R.Prashanthi et al. Formulation and In Vitro Evaluation of Controlled Release Matrix Tablets
of Flurbiprofen. Indo American Journal of Pharm Research.2014:4(12).

5686

Corresponding author
P.Naga Haritha
M.Pharm
Assistant Professor,
Department of Pharmaceutics,
St.Pauls college of Pharmacy, Turkayamjal,
Hayathnagar, RR Dist, Telangana, India.
harithasunilp@gmail.com

Vol 4, Issue 12, 2014.

R.Prashanthi et al.

ISSN NO: 2231-6876

INTRODUCTION
Oral drug delivery: [1, 2, 3, 11]
This is the most widely utilized route of administration among all the routes that have been explored for systemic delivery of
drugs via pharmaceutical products of different dosage form. Oral route is considered most natural, uncomplicated, convenient and safe
due to its ease of administration, patient acceptance and cost effective manufacturing process.
The term modified-release drug product is used to describe products that alter the timing and/or the rate of release of the drug
substance. A modified-release dosage form is defined "as one for which the drug-release characteristics of time course and/or location
are chosen to accomplish therapeutic or convenience objectives not offered by conventional dosage forms such as solutions,
ointments, or promptly dissolving dosage forms as presently recognized".
Extended-release drug products: A dosage form that allows at least a twofold reduction in dosage frequency as compared to
that drug presented as an immediate-release (conventional) dosage form. Examples of extended-release dosage forms include
controlled-release, sustained-release, and long-acting drug products.
Delayed-release drug products: A dosage form that releases a discrete portion or portions of drug at a time or at times other
than promptly after administration, although one portion may be released promptly after administration. Enteric-coated dosage forms
are the most common delayed-release products.
Targeted-release drug products: A dosage form that releases drug at or near the intended physiologic site of action. Targetedrelease dosage forms may have either immediate- or extended-release characteristics.
The term controlled-release drug product was previously used to describe various types of oral extended-release-rate dosage
forms, including sustained-release, sustained-action, prolonged-action, long-action, slow-release, and programmed drug delivery
Controlled release drug delivery system: [4, 5, 6, 9]
The US FDA defines sustained release dosage form as one that allows a reduction in dosing frequency from that necessitated
by a conventional dosage form, such as solution or an immediate release dosage form.
Drug Candidates for Controlled Release Products
To be a successful sustained release product the drug must be released from the dosage form at a predetermined rate,
dissolve in gastro intestinal fluids, maintain gastro intestinal residence time and be absorbed at a rate that will replace the amount of
drug being metabolized and excreted.
Characteristics of Controlled release products.
1. They exhibit neither very slow nor very fast rates of absorption and excretion.
2. They are uniformly absorbed from gastro intestinal tract.
3. They are administered in relatively small dosages.
4. They possess a good margin of safety.
5. They are used in the treatment of chronic rather than acute conditions.
Advantages of Controlled release dosage forms over conventional dosage forms
1. Less fluctuation in drug blood levels.
2. Reduction in dosing frequency
3. Enhanced convenience and compliance.
4. Reduction in adverse side effects.
5. Reduction in overall health care cost.

www.iajpr.com

Page

Controlled Release Technology For Oral Dosage Form. [11 14]


For orally administered dosage forms, Sustained release action is achieved by affecting the rate at which drug released from
the dosage form and or by slowing the transit time of the dosage form through the gastro intestinal tract.
The rate of drug release from solid dosage forms may be modified by the technologies which in general are based on
a. Modifying drug dissolution by controlling access of biological fluids to the drug through the use of barrier coatings.
b. Controlling drug diffusion rates from dosage forms.
c. Chemical reaction or interaction between the drug substance and its pharmaceutical barrier and site specific biological fluids.
d. Coated beads, granules, microspheres
In these systems the drug is distributed onto beads, pellets, granules or other particulate systems. Using conventional pan
coating or air suspension coating the solution of drug substance is placed on small inert nonpareil seeds or beads made of sugar and
starch or on micro crystalline cellulose spheres.

5687

Disadvantages:
1. Loss of flexibility in adjusting the drug dose and or dosage regimen and a risk of sudden and total drug release or dose dumping
due to a failure of technology.
2. Sustained release products contain a higher drug load and thus any loss of integrity of the release characteristics of the dosage
form has potential problems.
3. They should be never crushed or chewed, as the slow release characteristics may be lost and toxicity may result. This is
particularly important in patients unable to follow whole tablets, a problem commonly effecting in the elderly.
4. The large size of Sustained release product may cause difficulties in ingestion or transit to the gut.

Vol 4, Issue 12, 2014.

R.Prashanthi et al.

ISSN NO: 2231-6876

Flurbiprofen [15]
Flurbiprofen, a propionic acid derivative, is a nonsteroidal anti-inflammatory agent (NSAIA) with antipyretic and analgesic
activity. Oral formulations of Flurbiprofen may be used for the acute or long-term symptomatic treatment of rheumatoid arthritis,
osteoarthritis and anklylosingspondylitis. It may also be used to treat pain associated with dysmenorrhea and mild to moderate pain
accompanied by inflammation (e.g. bursitis, tendonitis, soft tissue trauma). Flurbiprofen may also be used topically prior to ocular
surgery to prevent or reduceintraoperative miosis. Flurbiprofen is structurally and pharmacologically related to fenoprofen, ibuprofen,
and Ketoprofen. This compound belongs to the biphenyls and derivatives. These are Organic compounds containing to benzene rings
linked together by a C-C bond. The commercially available Flurbiprofen is a racemic mixture of (+) S- and (-) R-enantiomers. The Senantiomer appears to possess most of the anti-inflammatory, while both enantiomers may possess analgesic activity. Similar to other
NSAIAs, the anti-inflammatory effect of flurbiprofenoccurs via reversible inhibition of cyclooxygenase (COX), the enzyme
responsible for the conversion of arachidonic acid to prostaglandin G2 (PGG2) and PGG2 to prostaglandin H2 (PGH2) in the
prostaglandin synthesis pathway. This effectively decreases the concentration of Prostaglandins involved in inflammation, pain,
swelling and fever.
Flurbiprofen is a non-selective COX inhibitor and inhibits the activity of both COX-1 and -2. It is also one of the most potent
NSAIAs in terms of prostaglandin inhibitory activity.Fluribiprofen is rapidly and almost completely absorbed following oral
administration. Peak plasma concentrations are reached 0.5 - 4 hours after oral administration. > 99% protein bound, primarily to
albumin. Binds to a different primary binding site on albumin than anticoagulants, sulfonamides and phenytoin. Flurbiprofen is poorly
excreted into human milk. Following dosing with Flurbiprofen, less than 3% of Flurbiprofen is excreted unchanged in the urine, with
about 70% of the dose eliminated in the urine as parent drug and metabolites. Renal elimination is a significant pathway of elimination
of Flurbiprofen metabolites.LD50=10 mg/kg (orally in dogs). Selective COX-2 inhibitors have been associated with increased risk of
serious cardiovascular events (e.g. myocardial infarction, stroke) in some patients. Current data is insufficient to assess the
cardiovascular risk of Flurbiprofen. Flurbiprofen may increase blood pressure and/or cause fluid retention and edema. Use caution in
patients with fluid retention or heart failure. Risk of GI toxicity including bleeding, ulceration and perforation. Risk of direct renal
injury, including renal papillary necrosis. Anaphylactoid and serious skin reactions (e.g. exfoliative dermatitis, Stevens-Johnson
syndrome, and toxic epidermal necrolysis) may occur. Common adverse events include abdominal pain, constipation, diarrhoea,
dyspepsia, flatulence, GI bleeding, GI perforation, nausea, peptic ulcer, vomiting, renal function abnormalities, anaemia, dizziness,
edema, liver function test abnormalities, headache, prolonged bleeding time, pruritus, rash, tinnitus. Although rarely documented in
the case of Flurbiprofen, oral propionic acid derivatives have been associated with a relatively high frequency of allergic reactions.
Osteoarthritis [16]
Osteoarthritis (OA) also known as degenerative arthritis or degenerative joint disease or osteoarthritis, is a group of
mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include
joint pain, tenderness, stiffness, locking, and sometimes an effusion. A variety of causeshereditary, developmental, metabolic, and
mechanical deficitsmay initiate processes leading to loss of cartilage. When bone surfaces become less well protected by cartilage,
bone may be exposed and damaged. As a result of decreased movement secondary to pain, regional muscles may atrophy, and
ligaments may become more lax. Treatment generally involves a combination of exercise, lifestyle modification, and analgesics. If
pain becomes debilitating, joint surgery may be used to improve the quality of life. OA is the most common form of arthritis.

Page

MATERIALS & METHODS


Flurbiprofen was obtained as a gift sample from MSN Laboratories Pvt. Ltd, Hyderabad, India. Guar gum, Xanthan gum,
Sodium carboxy methyl cellulose, HPMC K 100, PVP K30, and microcrystalline cellulose were purchased from Merck Specialities
Pvt.Ltd, Mumbai, India. All the other ingredients used were of analytical grade and used as received.

5688

Rheumatoid arthritis (RA)


Rheumatoid arthritis is a chronic (long-term) disease. Rheumatoid arthritis symptoms can come and go, and each person with
RA is affected differently. Some people have long periods of remission. Their rheumatoid arthritis is inactive, and they have few or no
symptoms during this time. Other people might have near-constant rheumatoid arthritis symptoms for months at a stretch. Although
rheumatoid arthritis can involve different parts the body, joints are always affected. When the disease acts up, joints become inflamed.
Inflammation is the body's natural response to infection or other threats, but in rheumatoid arthritis inflammation occurs
inappropriately and for unknown reasons.
Flurbiprofen is a potent anti-inflammatory analgesic agent, indicated for acute and chronic treatment of rheumatoid arthritis,
osteoarthritis, and ankylosing spondylytis. It reaches the maximum concentration in the blood within 4.7 to 5.7 hours(C max)
.Flurbiprofen is rapidly and almost completely absorbed following oral administration. Peak plasma concentrations are reached 0.5 - 4
hours after oral administration, for this reason the drug was administered in multiple doses. To enhance the bioavailability and to
reduce the dosing frequency it is formulated as controlled release tablet.

www.iajpr.com

Vol 4, Issue 12, 2014.

R.Prashanthi et al.

ISSN NO: 2231-6876

Methods:
Determination of UV Absorption maxima: [17]
Flurbiprofen solution was prepared in 0.1 N HCL and diluted suitably. The UV spectrum of the solution was taken on Lab
India 3200 UV/Vis double beam Spectrophotometer. The Solution exhibited UV maxima at 245 nm. The procedure was repeated with
pH 6.8 phosphate buffer. The solution exhibited UV maxima at 249 nm
Preparation of Standard Calibration Curve of Flurbiprofen:
100 mg of Flurbiprofen was accurately weighed and dissolved in little amount of Methanol and make up the final volume up
to 100 ml with 0.1 N HCl (pH 1.2) to prepare stock solution. The 10 ml of stock solution was further diluted with 0.1 N HCl (pH 1.2)
in 100ml to get 100g/ml (working standard). Then 0.2,0.4,0.6.0.8,and 1 ml of working standard was taken in 10 ml standard
volumetric flask and made up the volume with 0.1N HCl to prepare 2g,4g,6g,8g, and 10g drug per ml solution. Then the
absorbance was measured in a UV spectrophotometer at 245 nm against 0.1 N HCl (pH 1.2) as blank. The procedure was repeated
with pH 6.8 phosphate buffer and absorbances were measured at 249nm.
Drug Excipients compatibility studies
Fourier transform infrared spectrophotometry (FTIR): [18]
Compatibility study of drug with the excipients was determined by FTIR Spectroscopy. The pellets were prepared at high
compaction pressure by using KBr and the ratio of sample to KBr is 1:100. The pellets thus prepare were examined and the spectra of
drug and other ingredients in the formulations were compared with that of the original spectra.
Preformulation parameters
Bulk Density (Db):
It is the ratio of total mass of powder to the bulk volume of powder. It was measured by pouring the weight powder (passed
through standard sieve # 20) into a measuring cylinder and initial weight was noted. This initial volume is called the bulk volume.
From this the bulk density is calculated according to the formula mentioned below. It is expressed in g/ml and is given by,
Db = M/ Vb
Where,
M is the mass of powder
Vb is the bulk volume of the powder.
Tapped Density (Dt):
It is the ratio of total mass of the powder to the tapped volume of the powder. Volume was measured by tapping the powder
for 750 times and the tapped volume was noted if the difference between these two volumes is less than 2%. If it is more than 2%,
tapping is continued for 1250 times and tapped volume was noted. Tapping was continued until the difference between successive
volumes is less than 2 % (in a bulk density apparatus). It is expressed in g/ml and is given by,
Dt = M / V t
Where,
M is the mass of powder
Vt is the tapped volume of the powder.
Angle of Repose ():
The friction forces in a loose powder can be measured by the angle of repose (q). It is an indicative of the flow properties of
the powder. It is defined as maximum angle possible between the surface of the pile of powder and the horizontal plane
tan() = h / r
= tan-1 (h / r)

Page

5689

Where,
is the angle of repose.
h is the height in cm
r is the radius in cm
The powder mixture was allowed to flow through the funnel fixed to a stand at definite height (h). The angle of repose was
then calculated by measuring the height and radius of the heap of powder formed. Care was taken to see that the powder particles slip
and roll over each other through the sides of the funnel. Relationship between angle of repose and powder flow property.

www.iajpr.com

Vol 4, Issue 12, 2014.

R.Prashanthi et al.

ISSN NO: 2231-6876

Carrs index (or) % compressibility:


It indicates powder flow properties. It is expressed in percentage and is give by,

Where, Dt is the tapped density of the powder and


Db is the bulk density of the powder.
Hausners ratio:
Hausners ratio is an indirect index of ease of powder flow. It is calculated by the following formula.

Where, Dt is the tapped density, Db is the bulk density.


Lower Hausners ratio (<1.25) indicates better flow properties than higher ones (>1.25).
Formulation development of Tablets:
Formulation of Flurbiprofen Controlled release Tablet by Direct- Compression:
Composition of preliminary trials for Flurbiprofen Controlled release matrix Tablet by direct compression is shown in table
below. All the ingredients were weighed. Required quantity of drug and excipient mixed thoroughly in a mortar. The blend is
compressed using rotary tablet machine-8 station with 12mm flat punch, B tooling. Each tablet contains 200mg of Flurbiprofen and
other pharmaceutical ingredients.
Table 1: Formulations of Flurbiprofen controlled release matrix tablets.
Name of the material
Flurbiprofen
HPMC K100
Sodium CMC
Xanthan Gum
Guar gum
PVP K30
Talc
Magnesium stearate
MCC
Total

F F F F F F F F
F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
200 200 200 200 200 200 200 200 200 200
50 100 150 - - - - - - - - - 50 100 150 - - - - - - - - - 50 100 150 - - - - - - - - - 50
25 25 25 25 25 25 25 25 25 25
5 5 5 5 5 5 5 5 5 5
5 5 5 5 5 5 5 5 5 5
215 165 115 215 165 115 215 165 115 215
500 500 500 500 500 500 500 500 500 500

F F
F11
200
100
25
5
5
165
500

F
F12
200
150
25
5
5
115
500

All the ingredients are expressed in mg only

Thickness:
Tablet thickness is an important characteristic in reproducing appearance. Three tablets were selected randomly from each
batch and thickness was measured by using Vernier Calipers. Average thickness for tablets is calculated and presented with deviation.

www.iajpr.com

Page

Hardness:
Hardness or tablet crushing strength (fc), the force required to break a tablet in a diametric compression was measured using
Monsanto hardness tester. It is expressed in kg/cm2. Hardness of tablet is defined as the force applied across the diameter of the tablet
in order to break the tablet. The resistance of the tablet to chipping, abrasion or breakage under condition of storage transformation and
handling before usage depends on its hardness. For each formulation, the hardness of three tablets was determined and the average is
calculated and presented with deviation.

5690

Post compression parameters: [19 21]


Weight variation:
20 tablets were selected randomly from the lot and weighted individually to check for weight variation. Weight variation
specification is as per I.P.

Vol 4, Issue 12, 2014.

R.Prashanthi et al.

ISSN NO: 2231-6876

Friability (F):
Friability of the tablet determined using Roche friabilator. This device subjects the tablet to the combined effect of abrasion
and shock in a plastic chamber revolving at 25 rpm and dropping a tablet at the height of 6 inches in each revolution. Pre weighed
sample of tablets was placed in the friabilator and were subjected to the 100 revolutions. Tablets were dusted using a soft muslin cloth
and reweighed. The friability (F) is given by the formula.

In-Vitro drug release:


Invitro dissolution studies were carried out by using 900ml of 0.1 N HCl in USP dissolution apparatus by using paddle
method for about 2 hours. After 2 hours the dissolution medium was withdrawn keeping the tablet in the dissolution basket. Then pH
6.8 phosphate buffer was added to the dissolution medium (900ml) and the dissolution was carried out for about 10 hours. The
samples were withdrawn at regular time intervals of 30 min, 1 hour, 2 hr, 3,4,5,6,7,8,9 & 10 hours respectively.
Assay:
10 tablets were weighed and triturated. The tablet triturate equivalent to 10 mg of the drug was weighed accurately, dissolved
in pH 1.2 buffer and diluted to 100 ml with the same. Further dilutions were done suitably to get a concentration of 10 g/ ml with
simulated gastric fluid pH 1.2. Absorbance was read at 245 nm against the reagent blank, and the concentrations of Flurbiprofen in g/
ml was determined by using the regression equation.
Y = 0.007x + 0.001
Drug content in mg / tablet = conc. g/ml * dilution factor
% Drug content = drug content in mg * 100 / label claim.
% Drug content = drug content in mg * 100 / label claim.

Standard Calibration curve of Flurbiprofen in pH 6.8 Phosphate buffer:


The max for Flurbiprofen by UV spectrophotometric method is found at 249.0 nm in pH 6.8 Phosphate buffer had good
reproducibility and this method was used in the study.
Graph of Flurbiprofen was taken in pH 6.8 buffer at 249 nm. The correlation coefficient for the standard curve was found to
be closer to 1, at the concentration range, 2-10g/ml. The regression equation generated was y = 0.088x.

www.iajpr.com

Page

Fig.1: Standard graph of Flurbiprofen in 0.1 N HCl.

5691

RESULTS & DISCUSSION


Standard Calibration curve of Flurbiprofen in 0.1N Hydrochloric acid:
The max for Flurbiprofen by UV spectrophotometric method is found at 245.0 nm in 0.1N Hydrochloric acid had good
reproducibility and this method was used in the study.
Graph of Flurbiprofen was taken in Simulated Gastric fluid i.e pH 1.2 buffer at 245 nm. The correlation coefficient for the standard
curve was found to be closer to 1, at the concentration range, 2-10g/ml. The regression equation generated was y = 0.047x.

Vol 4, Issue 12, 2014.

R.Prashanthi et al.

ISSN NO: 2231-6876

Fig.2: Standard graph of Flurbiprofen in pH 6.8 Phosphate buffer Drug Excipients compatability studies.
(A) Fourier Transform-Infrared Spectroscopy:

Fig.3: FTIR spectra of pure Flurbiprofen.

Page

5692

Fig.4: FTIR spectra of Flurbiprofen + guar gum.

www.iajpr.com

Vol 4, Issue 12, 2014.

R.Prashanthi et al.

ISSN NO: 2231-6876

Fig.5: FTIR spectra of Flurbiprofen + HPMC K 100 M.

Fig.6: FTIR spectra of Flurbiprofen + Sodium CMC.

Fig.7: FTIR spectra of Flurbiprofen + Xanthan gum

1
2
3
4
5

Functional groups
present
CF (Aliphatic)
C=O
(Aliphatic )
CH (Aliphatic )
CO
( Aliphatic)
OH
( Aliphatic)

Frequency
cm-1
1400 1000

1370

Flurbiprofen+
Guar gum
1374

Flurbiprofen+
HPMC K100M
1374

Flurbiprofen+
sodiumCMC
1389

Flurbiprofen+
Xanthan gum
1389

1900 1600

1630

1632

1653

1631

1636

2960 2800

2881

2890

2890

2876

2875

1300 900

1128

1155

1155

1133

1135

1200 1500

1454

1454

1458

1454

1455

Flurbiprofen

www.iajpr.com

Page

S.No

5693

Table 2: IR interpretation of Flurbiprofen with various polymers used in the formulations.

Vol 4, Issue 12, 2014.

R.Prashanthi et al.

ISSN NO: 2231-6876

On performing the FTIR for pure drug as well as for the different polymers that are used in the formulation from the above graphs and
tabular column it was evident that there is no incompatibility seen for Flurbiprofen with any of the polymers used.
Evaluation Parameters
Pre-compression parameters:
The datas were shown in Table: 3.The values for angle of repose were found in the range of 23-27. Bulk densities and
tapped densities of various formulations were found to be in the range of 0.37 to 0.42 (gm/cc) and 0.45 to 0.49 (gm/cc) respectively.
Carrs index of the prepared blends fall in the range of 14 % to 20 %. The Hausners ration fall in range of 1.17 to 1.23. From the
result it was concluded that the powder blends had good flow properties and these can be used for tablet manufacture.
Table 3: Pre-compression parameters.
Formulations Bulk density (gm/cm2) Tap Density (gm/cm2)
F1
0.390.005
0.470.02
F2
0.380.01
0.460.02
F3
0.370.01
0.450.01
F4
0.390.02
0.460.05
F5
0.410.05
0.480.02
F6
0.400.03
0.490.005
F7
0.370.03
0.460.01
F8
0.410.005
0.480.01
F9
0.410.005
0.490.005
F10
0.400.02
0.470.01
F11
0.420.01
0.490.005
F12
0.390.005
0.480.01
n=3S.D (All the values are average of three determinations

Carrs Index (%)


17.020.01
17.390.01
17.770.01
15.210.02
14.580.01
18.360.03
19.560.01
14.580.02
16.320.01
14.890.005
14.280.02
18.750.1

Hausners ratio
1.200.005
1.210.005
1.220.005
1.180.005
1.170.005
1.220.005
1.240.01
1.170.01
1.190.01
1.170.005
1.170.005
1.230.1

Angle Of Repose()
24.910.01
24.230.02
25.340.03
26.710.03
25.340.02
26.230.05
23.340.02
24.780.01
23.780.03
26.680.02
25.700.05
26.710.03

Post compression Parameters:


Weight variation test:
Tablets of each batch were subjected to weight variation test, difference in weight and percent deviation was calculated for
each tablet and was shown in the Table: 4. the average weight of the tablet is approximately in range of 489 to 515 mg, so the
permissible limit is 5%. The results of the test showed that, the tablet weights were within the pharmacopoeia limit.
Hardness test:
Hardness of the three tablets of each batch was checked by using Pfizer hardness tester and the datas were shown in Table:
4. the results showed that the hardness of the tablets is in range of 4.1 to 4.5 kg/cm2, which was within IP limits.
Thickness:
Thickness of three tablets of each batch was checked by using Vernier Caliper and data shown in Table: 4. the result showed
that thickness of the tablet is raging from 4.85 to 5.08 mm, which was within IP limits.
Friability:
Tablets of each batch were evaluated for percentage friability and the datas were shown in the Table: 4. the average friability
of all the formulations lies in the range of 0.36 to 0.49 % which was less than 1% as per official requirements of IP.

F1
F2
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12

Weight variation
(mg)
5091
4981
5081.52
5111.5
4960.57
5131
5091
5070.5
5150.5
5111
4890.52
5030.52

Hardness (kg/cm2)
4.40.05
4.20.05
4.20.1
4.20.05
4.10.05
4.30.1
4.40.1
4.50.05
4.40.05
4.40.1
4.30.1
4.20.05

www.iajpr.com

Thickness
(mm)
4.90.005
5.060.02
5.010.01
4.890.005
4.960.01
4.850.01
5.080.01
5.020.005
4.940.005
5.080.03
5.010.01
4.860.02

Friability
(%)
0.390.05
0.380.01
0.430.03
0.470.01
0.450.05
0.380.05
0.490.02
0.360.02
0.370.02
0.430.05
0.480.05
0.430.02

Page

FD

5694

Table.4: Post compression Parameters.

Vol 4, Issue 12, 2014.

R.Prashanthi et al.

ISSN NO: 2231-6876

n=3S.D (All the values are average of three determinations).


Drug release study by in-vitro drug dissolution
Invitro dissolution studies were carried out by using 900ml of 0.1 N HCl in USP dissolution apparatus by using paddle
method for about 2 hours. After 2 hours the dissolution medium was withdrawn keeping the tablet in the dissolution basket. Then pH
6.8 phosphate buffer was added to the dissolution medium (900ml) and the dissolution was carried out for about 10 hours. The
samples were withdrawn at regular time intervals of 30 min,1 hour,2 hr,3,5,5,6,7,8,9,10,11& 12 hours respectively. The results were
displayed in table: 5, 6, 7 & 8 and fig. 8 & 9.
Table 5: Cumulative percentage drug release for F1, F2 and F3 formulations.
Time(Hrs)
F1
F2
F3

0.5
12.15
9.65
5.62

1
21.32
15.64
8.46

2
30.26
20.15
14.25

3
39.56
26.45
19.72

4
45.36
32.54
25.64

5
52.36
40.45
30.45

6
60.15
46.25
34.51

7
69.78
51.29
40.12

8
77
58.97
46.35

9
85.45
64.35
52.31

10
92.15
70.6
59.76

11
99.65
78.64
64.31

12
-85.64
71.64

Table 6: Cumulative percentage drug release for F4, F5 and F6 formulations.


Time(Hrs)
F4
F5
F6

0.5
25.64
20.35
18.65

1
46.89
35.15
26.46

2
61.25
51.02
39.17

3
80.36
62.45
49.26

4
99.56
76.26
57.61

5
85.15
68.64

6
98.65
81.21

7
97.25

8
-

9
-

10
-

11
-

12
--

11
-

12
--

Table 7: Cumulative percentage drug release for F7, F8 and F9 formulations.


Time(Hrs)
F7
F8
F9

0.5
25.16
18.26
16.32

1
44.36
31.47
24.45

2
61.46
47.31
36.34

3
83.64
63.85
49.45

4
98.65
77.56
61.12

5
89.15
70.36

6
98.64
82.67

7
97.26

8
-

9
-

10
-

Table 8: Cumulative percentage drug release for F10, F11 and F12 formulations.
1
20.34
19.54
19.16

2
28.46
27.36
25.39

3
35.02
34.94
31.09

4
46.56
42.64
39.95

5
53.15
50.25
46.62

6
68.45
59.64
55.23

7
79.46
67.46
63.38

8
86.5
75.25
70.06

9
99.45
84.46
79.77

Fig.8: Cumulative percentage drug release for F1- F6 formulations.

10
91.56
86.64

11
98.36
91.45

12
-99.18

5695

0.5
13.51
10.23
13.23

Page

Time(Hrs)
F10
F11
F12

www.iajpr.com

Vol 4, Issue 12, 2014.

R.Prashanthi et al.

ISSN NO: 2231-6876

Fig.9: Cumulative percentage drug release for F7- F12 formulations.


From the dissolution data it was evident that the formulations prepared with Sodium CMC and Xanthan gum as polymers
were unable to retard the drug release up to desired time period i.e., 12 hours.
Whereas the formulations prepared with Guar gum retarded the drug release in the concentration of 150 mg showed required
release pattern i.e., retarded the drug release up to 12 hours and showed maximum of 99.18 % in 12 hours with good retardation.
The formulations prepared with HPMC K100M showed more retardation even after 12 hours they were not shown total drug
release. Hence they were not considered
Application of Release Rate Kinetics to Dissolution Data:
Various models were tested for explaining the kinetics of drug release. To analyze the mechanism of the drug release rate
kinetics of the dosage form, the obtained data were fitted into zero-order, first order, Higuchi, and korse mayer Peppas release model.
Table.9: Release Rate Kinetics data for Optimized formula.
S.No.

Type of graph

R value

Zero order release kinetics

0.992

First order release kinetics

0.873

Higuchi release kinetics

0.958

4.

Korse mayer Peppas

0.978

www.iajpr.com

Page

REFERENCES
1. Ansel H., Allen L &Jr.popovich N. Ansels pharmaceutical Dosage Forms and Drug delivery systems, 8 th edition, 2004; 260-268.
2. Aulton M. The science of dosage form design, International student edition, published by churchil Livingston, 2002; 304321,347-668.
3. Banker GS. Modern pharmaceutics, 3rd edition marcel dekkerinc, Newyork. 576-820.
4. Bramhanker DM, .Jaiswal SB. Controlled release medications. In: Biopharmaceutics and Pharmacokinetics a treatise, 1995; 335375.
5. Chien YW. Controlled and modulated-release drug delivery systems, 1995;281-313 Donald L. Hand book of pharmaceutical
controlled release technology, 2002; 466-471,738-739.
6. Durgacharan A Bhagwat., Pravin S Kawtikwar., Dinesh M Sakarkar. Formulation and the in-vitro and biopharmaceutical
evaluation of sustained release tablet of verapamil HCL using precirol ATO 5 through melt granulation technique. 2009; 278285.
7. Government of India Ministry of Health and Family Welfare. 1999.The Pharmacopoeia of India. Delhi, India, Controller of
Publication.312-314.

5696

CONCLUSION
The main aim of the study was achieved by formulating controlled release matrix tablets of Flurbiprofen. All the polymers
that were used in the formulation had shown no incompatibility with the drug. Both precompression and post compression parameters
for the formulations were within the I.P. limits. Among all the formulations prepared F12had shown good retarding property and
controlled the release up to 12hrs with a maximum drug release of 99.18%.

Vol 4, Issue 12, 2014.

18.

19.
20.
21.

G.naresh kumar, Shubhrajit Mantry, Arpita Ghosh, L.Rajesh Patro, A.Hemanth. formulation and evaluation of controlled release
matrix tablets of Glipizide. Indo American journal of Pharm research. 2013:3(7).
Kuchekar., Indian journal of pharma education. 2 nd edition. 2001;150-152
Lachman L.,. The Theory of practice of Industrial pharmacy, 3rd edition, published by Lea &Febiger, 1986; 293-345,346-373.
Raymond C Rowe., Paul J Sheskey& Sian C Owen.,. Handbook of Pharmaceutical Excipients, 6 theditition, 2009; 622-624.
Raymond C Rowe., Paul J Sheskey& Sian C Owen.,.Handbook of Pharmaceutical Excipients, 6 th editition, 2009;129-133.
Raymond C Rowe., Paul J Sheskey& Sian C Owen. Handbook of Pharmaceutical Excipients, 6th editition; 2009; 581-585.
Raymond C Rowe., Paul J Sheskey& Sian C Owen., Handbook of Pharmaceutical Excipients, 6 th editition, 2009;326-329.
Raymond C Rowe., Paul J Sheskey& Sian C Owen.,. Handbook of Pharmaceutical Excipients, , 6theditition, 2009;404-407.
Remington J. The science and practice of pharmacy, 21 st Edition, published by Lippincott Williams & Wilkins, 2005(1);941-948.
Hardik Soni, Ghanshyam Patel, Megha Shah, Mayank Panchal, Krishna Murti.
Evaluation of anti-arthritic activity of Dazzle
ointment - A polyherbal formulation. International Journal of Pharmacology and Clinical Sciences 2013; 2: 14-18.
Ashtamkar Joel, NangudeShantaramand, ChughNaresh. Formulation and Evaluation of Controlled Release Tablets of Labetalol
Hydrochloride Using Hydrophobic Polymers. International Journal of Research in Pharmaceutical and Biomedical Sciences 2013;
4: 380-384.
Mohammad Usman, Irshad Ali, Hafsa Bibi, Javeid Iqbal and Kashif Iqbal. Preparation and Evaluation of Controlled Release
Tablets Containing Mefenamic Acid Open Access. Clinical and Experimental Pharmacology 2012;2:1-3
R.Margret chandira, Debjit Bhowmik, Rahul Yadav, B.Jayakar, K. P. Sampath Kumar. Formulation and Evaluation the Oral
Tablets Ibuprofen. The Innovation 2012; 1: 32-43.
Girish.B, Ismail pasha, Gowda DV. Formulation and evaluation of Sustained release matrix tablets of Flurbiprofen using Guar
gum Research Article Int J Pharm Sci,2012; 4; 5:120-123.

54878478451141211

5697

9.
10.
11.
12.
13.
14.
15.
16.
17.

ISSN NO: 2231-6876

Page

8.

R.Prashanthi et al.

www.iajpr.com