World Journal of Pharmaceutical research - WJPR!

Patel Sunilkumar World Journal of Pharmaceutical research
Article Received on
07 September 2012,
DESIGN AND IN VITRO EVALUATION OF NOVEL IBUPROFEN
www.wjpr.net
SUSTAINED RELEASE MATRIX TABLETS BASED ON
COMBINATION OF HYDROPHILIC AND HYDROPHOBIC MATRIX
SYSTEM
*Patel Sunilkumar A., Patel Jitendra L.
Shree Krishna Institute of Pharmacy College, Shankhalpur, Becharaji 384210 Mehsana,
Revised on 25September2012,
Accepted on 25 October 2012
*Correspondence for
Author:
* Patel Sunilkumar A
Shree Krishna Institute of
Pharmacy College, sankhalpur,
becharaji-384210,
Mehsana,India
sunil.pharma1988@rediffmail.
com
World Journal of Pharmaceutical research
Volume 1, Issue 5, 1330-1341. Research Article ISSN 2277 – 7105
ABSTRACT
Gujarat, India.
Hydroxypropyl and Ethyl cellulose are matrix polymer can be used in
formulation of sustained release dosage form of slightly water soluble
drug. It was decided to study the effect of these hydrophilic and
hydrophobic polymers at different matrix polymer ratio, on release
profile of drug from matrix formulation prepared using hydrophilic
and hydrophobic matrix system and both matrix systems in different
ratio used. Ibuprofen was considered as ideal drug for sustained
release formulation. The sustained release matrix of Ibuprofen were
prepared by wet granulation technique in differ matrix polymers ratio.
Drug release study was carried out using BP apparatus 2 with pH 7 for
12 hr at 1 hr interval. During dissolution study different parameters
such as effect of different matrix polymers ratio like HPMC: EC was
carried out. The results of dissolution study showed that the release of
drug from Matrix prepared from different ratio of both HPMC and EC gets more retarded than
from HPMC and EC alone.
KEY WORDS: Ibuprofen, HPMC K 4 M, EC, PEG 600, Lactose.
INTRODUCTION
Ibuprofen is chiral propionic acid derivative belonging to the class of non-steroidal anti-
inflammatory drugs (NSAIDs). Due to its analgesic, antipyretic and anti inflammatory
actions it is used in the treatment of inflammatory condition such as rheumatoid arthritis,
1330

Patel Sunilkumar World Journal of Pharmaceutical research
osteoarthritis, ankylosing spondylitis, mild and moderate pain, dysmenorrhoea, vascular
heads and fever. The dose level as an anti-rheumatic for adults is about 1.2 to 3.2 g orally per
day in 3 or 4 divided doses. The common dosage ranges are tablets with 200 mg, 400 mg, 600
mg and 800 mg and slow release tablets with 800 mg. The OTC dosage forms are mainly the
200 mg and 400 mg forms (except for the United States and other countries, here the 200 mg
forms is the only OTC form). Ibuprofen is readily absorbed by the gastrointestinal tract. The
peak plasma levels are reached within 1 – 2 h. After an oral dose of 200 – 400 mg, 15 – 25
mg/ml appear in the blood serum. Ibuprofen has an extensive protein binding capacity (99%).
Ibuprofen is excreted via the kidneys. The biological half-life is 2 hours. After 24 h 100% of
the active substance is excreted in the urine. [1,2]
Ibuprofen is slight soluble in water, and hence judicious selection of release-retarding
excipients is necessary to achieve a constant in vivo input rate of the drug. Most commonly
used method of modulating the drug release is to include it in a matrix system. Because of
their flexibility, hydrophilic polymer matrix systems are widely used in oral controlled drug
delivery to obtain a desirable drug release profile, cost effectiveness, and broad regulatory
acceptance. hence, in the present work and attempt has been made to develop once-daily
sustained release matrix tablets of Ibuprofen using hydrophilic matrix materials and
hydrophobic material such as hydroxypropylmethylcellulose (HPMC), Ethyl Cellulose(EC)
and PEG 600. [3,4]
Drug release for extended duration, particularly for highly water-soluble drugs, using a
hydrophilic and Hydrophobic matrix system is restricted because of rapid diffusion of the
dissolved drug through the hydrophilic and hydrophobic gel network. For such drugs with
high water solubility, hydrophobic polymers are suitable, along with a hydrophilic matrix for
developing sustained-release dosage forms. Hydrophobic polymers provide several
advantages, ranging from good stability at varying pH values and moisture levels to well
established safe applications. Therefore, in this study, the hydrophobic polymers like ethyl
cellulose (EC) were used. Main objective of study was to formulate and evaluation of
sustained release dosage form by different polymer material to investigate the effect of
Polymer. [8]
www.wjpr.net
1331

Patel Sunilkumar World Journal of Pharmaceutical research
MATERIAL AND METHODS
MATERIAL
Ibuprofen was procured from Ratmani Pharmaceutical pvt Ltd Mehsana. Hydroxypropyl
methylcellulose K4M (HPMC K4M) was obtained from Purui Enterprise pvt ltd Ahmedabad.
Ethyl Cellulose was obtained from Chemeco company pvt ltd Ahmedabad.PEG was obtained
from Shital Chemical, Ahmedabad. Lactose, Magnesium stearate, and talc were purchased
from Shital Chemical pvt ltd, Ahmedabad. All other materials and chemicals used were of
either pharmaceutical or analytical grade.
METHODS
Tablet Preparation
Ibuprofen Sustained Release matrix tablets were prepared by Wet granulation technique. 7,8
Drug was passed through 40# sieve. HPMC K 4M, Ethyl cellulose, Lactose, PEG 400 were
passed through 30# sieve. All other ingredients were passed through 40# sieve. All
ingredients were mixed for 15-20 min. After mixing, Mg. stearate (60# sieve) and Talc were
added to mixer blend and mix again for 3-5 min. Prepared blend was compressed (10/30
diameter, flat punches) using Multi Rotary Tablet Machine (Type: Patel services pvt ltd,
Ahemdabad). Each tablet contains 200 mg of Ibuprofen and other pharmaceuticals
ingredients as listed in Table 1.
EVALUATION OF POWDER AND POWER BLEND
Angle of Repose
Angle of Repose of Power and Power blend were determined by the funnel method.
Accurately weight powder blend were taken in the funnel. Height of the funnel was adjusted
in such a way the tip of the funnel just touched the apex of the powder blend. Powder blend
was allowed to flow through the funnel freely on to the surface. Diameter of the powder cone
was measured and angle of repose was calculated using the following equation. [3],[4]
Tan α = h/r
DENSITY
Bulk Density (BD)
Weigh accurately 10 g of Power and Power blend, which were previously passed through 20#
sieve and transferred in 100 ml graduated cylinder. Carefully level the powder without
www.wjpr.net
1332

Patel Sunilkumar World Journal of Pharmaceutical research
compacting, and read the unsettled apparent volume (V0). Calculate the apparent bulk density
in gm/ml by the following formula. [3],[4]
Bulk density = Weigh of powder/ Bulk volume
Tapped Density (TD)
Weigh accurately 10g of Power and Power blend which were previously passed through 20#
sieve and transferred in 100 ml graduated cylinder. Then mechanically tap the cylinder
containing the sample by raising the cylinder and allowing it to drop under its own weight
using mechanically tapped density tester that provides a fixed drop of 14±2 mm at a nominal
rate of 300 drops per minute. Tap the cylinder for 500 times initially and measure the tapped
volume (V1) to the nearest graduated units, repeat the tapping an additional 750 times and
measure the tap volume (V2) to the nearest graduated units. If the difference between the two
volumes is less than 2% then final the volume (V2). Calculate the tapped bulk density in
gm/ml by the following formula. [3],[4]
Tapped density = Weigh of powder / Tapped volume
Carr’s Index
Compressibility index of Power and Power blend were determined by Carr’s compressibility
index. It was a simple test to evaluate the BD and TD of a powder and the rate at which it
packed down [3],[4] . The formula for Carr’s index is as below:
Hausner’s Ratio
www.wjpr.net
Carr’s index (%) = [(TD-BD)*100] / TD
Hausner’s Ratio is a number that is correlated to the flowability of Power and Power blend.
[3],[4]
Husner’s Ratio = TD / BD
EVALUATION OF TABLETS
Thickness
Thickness of the tablets was determined using a vernier caliper (Sunil Corporation pvt Ltd,
Nadiad). [3]
1333

Patel Sunilkumar World Journal of Pharmaceutical research
Weight Variation Test
To study weight variation, 20 tablets of each formulation were weighed using an electronic
balance (Digital Weighing Balance, Purvi Enterprise pvt Ltd Ahmedabad), and the test was
performed according to the official method. [4]
Hardness
Hardness of the tablets was determined using a hardness testing apparatus (Monseto Type,
Sunil Corporation pvt Ltd, Nadiad). A tablet hardness of about 5-6 kg/cm2 is considered
adequate for mechanical stability. [4]
Friability
The friability of the tablets was measured in a Roche friabilator (Sunil Corporation pvt Ltd,
Nadiad ).Tablets of a known weight ( W0 ) or a sample of tablets are deducted in a drum for a
fixed time (100 revolutions) and weighed (W) again. Percentage friability was calculated
from the loss in weight as given in equation as below. The weight loss should not be more
than 1% w/w. [4]
www.wjpr.net
% Friability = (W0-W)/ W0 × 100
Percentages Friability of tablets less than 1% are considered acceptable.
IN VITRO RELEASE STUDIES
Dissolution profiles of the prepared tablets were determined u s in BP II rotating paddle
apparatus at 37 C ± 0.5 and a rotating speed of 50 rpm in a 900 ml distilled water. 5 ml of
sample was withdrawn after 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7,8 ,9,10,11 and 12 hours and was
replaced by an equal volume of fresh dissolution medium of same pH and Collected samples
were analyzed systronics UV/VIS double beam spectrophotometer 2203 at 265 nm. and
cumulative percent drug release was calculated. The Study was performed in triplicate. [10,11,12]
1334

Patel Sunilkumar World Journal of Pharmaceutical research
RESULT AND DISCUSSION
Standard Calibration Curve of Ibuprofen
Table 1: Absorbance data for the calibration curve of ibuprofen in ethanol at 265nm
www.wjpr.net
Absorbance
Sr no. Concentration
(µg/ml)
1 100 0.109
2 200 0.201
3 300 0.282
4 400 0.384
5 500 0.510
6 600 0.637
7 700 0.750
8 800 0.882
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
PURE IBUPROFEN
Absorbance
In ethanol
y = 0.001x - 0.031
R² = 0.994
0 500 1000
Time
Figure 1. Standard calibration curve of Ibuprofen in 0.1ethanol at 265 nm
1335

Patel Sunilkumar World Journal of Pharmaceutical research
Composition of Ibuprofen Sustained Release Tablets
Table 2: Different Formulation for Ibuprofen Sustained Release Tablet
www.wjpr.net
Ingredients F1 F2 F3 F4 F5 F6 F7
Ibuprofen 200 200 200 200 200 200 200
EC --- 100 -- -- -- -- --
HPMC 100 -- -- -- -- -- --
EC:HPMC -- -- 60:40 40:60 50:50 75:25 25:75
PEG 4000 7.2 7.2 7.2 7.2 7.2 7.2 7.2
Lactose 50.86 50.86 50.86 50.86 50.86 50.86 50.86
Magnesium
Stearate
1.94 1.94 1.94 1.94 1.94 1.94 1.94
*HPMC K4M and EC indicate Hydroxypropylmethylcellulose and Ethyl cellulose all batches
contained 200mg of Ibuprofen.
Pre-Compression Evaluations of Ibuprofen Sustained Matrix Tablets
Table 3: Physical Properties of Ingredients
Ingredient
(10gm)
Bulk
Density
(gm/cm 3 )
Tapped
Density
(gm/cm 3 )
Hausner’s
ratio
Card’s index
Angle of
Repose
Ibuprofen 0.555 0.588 1.06 5.61 26.29 0
HPMC 0.540 0.606 1.12 10.89 20.18 0
EC 0.298 0.322 1.08 7.45 22.25 0
Table 4: Evaluation of Different Power Blends
Batch
Code
Bulk
density
(gm/cm 3 )
Tapped
density
(gm/cm 3 )
Hausner’s
ratio
(HR)
Carr’s index
(Ic)
Angle of
repose
(ø)
F1 0.404 0.505 1.25 20.00 20.37 0
F2 0.394 0.476 1.20 17.22 22.56 0
F3 0.394 0.446 1.13 11.66 12.62 0
F4 0.381 0.469 1.23 18.76 17.90 0
F5 0.385 0.468 1.21 17.73 16.85 0
F6 0.340 0.432 1.27 21.29 17.96 0
F7 0.402 0.512 1.27 21.48 17.03 0
1336

Time
(hr)
Patel Sunilkumar World Journal of Pharmaceutical research
Post-Compression Evaluations of Ibuprofen Sustained Matrix Tablets
Table 5: Evaluation of Tablets
Batch
Code
In-Vitro Drug Release Studies
Table 6: In-Vitro Drug Release Studies of Ibuprofen sustained release tablets
www.wjpr.net
Weight
Variation
Average
Wt in
(mg)±SD
Hardness
(kg/cm 2 )
±SD
Diamete
r
(mm)
±SD
% Cumulative Release
Thicknes
s
(mm)
±SD
Friability
%±SD
Drug Release
%±SD
F1 259±5.0 4.4±0.5 8.5±0.03 5.5±0.01 0.56±0.01 81.99±0.56
F2 265±5.5 4.1±0.4 8.5±0.02 5.5±0.04 0.58±0.04 78.04±0.16
F3 255±5.1 3.4±0.6 8.5±0.04 5.3±0.02 0.63±0.02 71.34±0.96
F4 260±5.5 3.85±0.5 8.7±0.01 5.3±0.01 0.60±0.01 62.11±0.10
F5 270±5.1 3.5±0.3 8.5±0.02 5.3±0.03 0.62±0.03 68.47±0.51
F6 260±5.3 3.1±0.6 8.7±0.03 5.3±0.02 0.67±0.01 74.82±0.64
F7 255±5.1 3.80±0.4 8.5±0.01 5.3±0.01 0.59±0.02 65.23±0.15
F1±SD F2±SD F3±SD F4±SD F5±SD F6±SD F7±SD
0.5 18.05±0.56 17.09±0.10 15.01±0.57 12.06±0.49 14.03±1.21 16.07±1.01 13.01±0.53
1 24.23±1.11 23.51±0.38 21.14±0.51 18.32±0.85 20.44±0.54 22.02±0.64 19.19±0.52
2 31.24±1.07 29.05±0.50 26.71±0.70 23.12±0.70 25.62±0.47 27.37±0.44 24.11±0.81
3 37.44±0.83 35.19±0.01 31.57±0.60 27.79±0.66 30.21±0.99 33.03±0.19 28.89±0.24
4 43.01±0.54 41.17±0.17 37.56±0.52 31.32±0.44 35.23±1.56 39.69±0.63 33.46±1.03
5 49.59±0.12 46.21±0.98 42.09±0.78 35.37±0.32 40.34±0.90 44.12±0.39 37.34±1.15
6 54.43±0.04 51.34±1.13 47.39±0.17 39.55±1.26 44.83±0.46 49.58±0.94 41.21±0.21
7 59.32±0.49 56.48±1.04 51.52±0.66 42.71±0.24 48.42±0.30 54.66±0.50 45.33±0.46
8 64.49±1.09 61.55±0.41 55.66±0.54 46.93±0.06 52.69±0.23 58.81±0.87 49.51±0.31
9 68.62±1.07 65.69±0.60 59.75±0.45 50.56±0.68 56.88±0.47 62.93±0.51 53.73±0.66
10 72.86±1.06 69.77±0.02 63.92±0.35 54.71±0.48 60.99±0.62 66.44±0.72 57.91±0.49
11 77.18±0.76 73.82±0.76 67.09±0.09 58.86±0.88 64.26±0.59 70.65±0.28 61.62±0.27
12 1.99±0.40 78.04±0.25 71.34±0.62 62.11±1.17 68.47±1.12 74.82±0.54 65.23±0.34
1337

Patel Sunilkumar World Journal of Pharmaceutical research
Figure 2. In-vitro dissolution profiles for tablets of batches f1 to f7 (Using dissolution
apparatus)
Ibuprofen is chiral propionic acid derivative belonging to the class of non-steroidal anti-
inflammatory drugs (NSAIDs). Due to its analgesic, antipyretic and anti inflammatory
actions it is used in the treatment of inflammatory condition such as rheumatoid arthritis ,
osteoarthritis , ankylosing spondyolitis, mild and moderate pain, dysmenorrheal, vascular
heads and fever. The dose level as an anti-rheumatic for adults is about 1.2 to 3.2 g orally per
day in 3 or 4 divided doses. The common dosage ranges are tablets with 200 mg, 400 mg, 600
mg and 800 mg and slow release tablets with 800 mg. The OTC dosage forms are mainly the
200 mg and 400 mg form s (except for the United States and other countries, here the200 mg
form is the only OTC form). Ibuprofen is readily absorbed by the gastrointestinal tract. The
peak plasma levels are reached within 1 – 2 h. After an oral dose of 200 – 400 mg, 15 – 25
mg/ml appear in the blood serum. Ibuprofen has an extensive protein binding capacity (99%).
Ibuprofen is excreted via the kidneys. The biological half-life is about 2 hours. After 24 h
100% of the active substance is excreted in the urine.
Ibuprofen with all material that developments of sustained release dosage form. In study
HPMCk4M and Ethyl cellulose which were used in different Ratio and check optimize
weighting for suitable sustained release dosage and using hydrophilic matrix polymer and
hydrophobic matrix polymer resepectly. Batches of ibuprofen were formulated with using
HPMC K4M, Ethyl cellulose, PEG600, Lactose, magnesium stearate and talc shown table1.
www.wjpr.net
%Cumulative Release
90
80
70
60
50
40
30
20
10
0
0 5 10 15
Time in hr
BATCH1
BATCH2
BATCH3
BATCH4
BATCH5
BATCH6
BATCH7
1338

Patel Sunilkumar World Journal of Pharmaceutical research
Formulated Power blend of Different batches were Evaluated. Showed results of Power blend
have Bulk density and tapped density of F1 to F7 batches that 0.340 to 0.404 and 0.432 to
0.532 Respect. Carr’s Index and hausner’s ratio have good compare to std value as according
to IP of F1 to F7 batches that 11.66 to 21.48 and 1.13 to 1.27 shown table 3 Respect. Angle of
repose has good and Excellent as Compare standard value as According to IP of F1 to F7
Batches that 12.62 0 to 22.56 0 shown table3. Ibuprofen Tablets were Prepared successfully by
wet granulation Technique. In Weight variation test, the Pharmacopoeia limit for percent of
deviation for tablets of more than 260mg is ±5%. The average percent deviation of all tablets
was found to be limit and hence all formulations passed the weight variation test. The hardness
of tablets of all formulation was in range of 2.5±0.51 to 3.8±0.54 kg\cm 2 . The Thickness of
tablets ranged from 5.204±0.01 to 5.514±0.01.i.e. less than 1%. The Diameter of tablets
ranged from 8.301±0.01 to 8.520±0.01. The Friability of tablets of all formulation was in
range of 0.059±0.01 to 0.065±0.01shown table 4.All thickness shown uniform thickness. The
Drug content was found to be uniform all formulation and ranged from 62.11% to 81.99%.
Shown in figure1
CONCLUSION
Among all formulation f4 containing 40% of ehtylcellulose and 60% of Hydroxy propyl
methyl cellulose showed in vitro drug release 62.11% and which is equivalent to marketed
preparation hence considered as most promising formulation. Result also showed that among
hydrophilic and hydrophobic matrix polymer. HPMC sustain more than EC .Combination of
HPMC and EC retain drug more than that individual matrix polymer. In study concluded
HPMC and EC are hydrophilic and hydrophobic matrix polymer which using matrix foaming
agent by wet granular technique to sustain the release of ibuprofen.
ACKNOWLEDGEMENTS
We are grateful to Ratmani Pharmaceutical Ltd, Mehsana for providing gift sample of
Ibuprofen.
REFERENCES
1. Dabbagh M.A and Beitmashal L.Sustained Release Formulation and In-Vitro Evaluation
of Ibuprofen-Hpmc Matrix Tablets. Jundishapur J Natural Pharm Products, 2006; 1:1-7.
2. Prajapati Bhupendra G., Patel Krunal R.Design and In Vitro Evaluation of Novel
Nicorandil Sustained Release Matrix Tablets Based On Combination of Hydrophilic and
Hydrophobic Matrix System. Int J Pharm Sci. and Res, 2010; 1(1): 2143-2156.
www.wjpr.net
1339

Patel Sunilkumar World Journal of Pharmaceutical research
3. Subramaniam Kannan, Rangasamy Manivannan, Kugalur Ganesan Parthiban
Kakkatummal Nishad and Natesan Senthil Kumar. Formulation and Evaluation of
Sustained Release Tablets of Aceclofenac using Hydrophilic Matrix System. Int J Pharma
Tech Res, 2010; 2(3):1775-1780.
4. Raghavendra raon.G, Gandhi sagar, patel tarun.Formulation And Evaluation of Sustained
Release Matrix tablets of Tramadol Hydrochloride.Int J Pharm and pharmaceutical sci
,2009; 1(1):660-671.
5. Sahu Atul Kumar, Singh Shailendra Kumar and Verma Amita. Formulation
Development of Buoyant Controlled Release Tablets Containing Chitosan: Optimization
of In vitro Dissolution and Release Kinetics.Int J Pharma and Pharmaceutical Sci, 2011;
3(2):81-85.
6. Selvadurai Muralidharan, Subramania Nainar Meyyanathan, Kaliaperumal Krishnaraj 1
And Sekar Rajan .Development of oral Sustained release dosage form for low melting
chiral compound Dexibuprofen and it’s in vitro-in vivo evaluation. Int J Drug Dev, 2011;
3:492-502.
7. Shoaib M. Harris, tazeen japery, Merchant humid a. and yousuf Rabia Ismail. Evaluation
of Drug Release Kinetics from Ibuprofen Matrix Tablets Using Hpmc. Pakistan J Pharm
Sci, 2006; 19(2):119-124.
8. Tiwari Sandip B., Murthy T. Krishna, Pai M. Raveendra, Mehta Pavak R., and Chowdary
Pasula B.Controlled Release Formulation of Tramadol Hydrochloride Using Hydrophilic
and Hydrophobic Matrix System. American Association of pharm scientists Pharm Sci
Tech, 2003; 4(3):E31.
9. Bhagwat Durgacharan A, Kawtikwar Pravin S and Sakarkar Dinesh M. Sustained Release
Matrices of Verapamil HCl Using Glyceryl Monosterate and Stearic Acid.Res J Pharm
Tech, 2008; 1(4):405-409.
10. Yeole P.G., gatte UC, babla I B and nakhat PD. Design and Evaluation of Xanthan Gum-
based Sustained Release Matrix Tablets of Dichlofenac sodium. Ind J Pharm Sci, 2006;
185-189.
11. Senthil Kumar B, Prem Anand D C, Senthil Kumar K L, Saravanakumar M and
Thirumurthy R.Formulation and evaluation of diltiazem hydrochloride Extented release
tablet by melt granulation technique. Int J Pharm & Indu Res, 2011; 1(1): 36-42.
12. Saleh A. Al-Suwayeh, Mohammed H. El-Shaboury, Saeed M. Al-Baraki, Abubakar S.
Elgorashy and Ehab I. Taha. In Vitro and in Vivo Evaluation of Sustained Release
www.wjpr.net
1340

Patel Sunilkumar World Journal of Pharmaceutical research
Hydralazine Hydrochloride Tablets Prepared by Thermal Granulation Technique. Aus J
of Basic and Applied Sci, 2009; 3(3): 2866-2875.
www.wjpr.net
1341