Formulation and Evaluation of Microspheres Containing Aceclofenac

222
* Corresponding author: Yadagiri Phalguna
E-mail address: yphalgun@gmail.com
IJPAR |Volume 3 | Issue 2 | April-June-2014 ISSN: 2320-2831
Available Online at: www.ijpar.com
[Research article]
Formulation and Evaluation of Microspheres Containing
Aceclofenac
Y.Phalguna*, G.Supriya, A.Tejasvi, D.Narasimha, G.Gopala Krishna.
Jyothishmathi College of Pharmacy, Turkapally, Shamirpet, R.R.Dist.-500 078. A.P.
ABSTRACT
Aceclofenac, a non-steroidal anti-inflammatory drug (NSAID) The chemical name of aceclofenac is Glycolic
acid, [o(2,6 dichloroanilino) phenyl] acetate. Adverse effect of aceclofenac is headache, nausea, vomiting, bone
marrow problems, dizziness constipation. Elimination half-life is 4 hrs. The main objective of this research work
was to prepare hydroxyl propyl methyl cellulose and eudragit microspheres loaded with aceclofenac and invtro
relese study.In the present study, solvent evaporation method is used for preparation microspheres. The
polymers hydroxylpropyl methylcellulose and eudragit was dissolved and added to the 0.2% PVA solution and
stirred it for 2 hrs. Microspheres were spherical shape and smooth surface. Infrared spectra showed identical
peaks of drug and polymers. Drug entrapment efficiency was found to be (72.32%). In vitro release studies were
performed by using shaking flask method about (89.59 %) drug was released in 12 hrs.
Keywords: Aceclofenac, Microspheres, HPMC, Eudragit, Solvent evaporation.
INTRODUCTION
Novel drug delivery systems (NDDS) offer many
advantages1
, which include improved therapy by
increasing the efficacy and duration of drug
activity, increased patient compliance through
decreased dosing frequency and convenient routes
of administration, and improved targeting for a
specific site to reduce unwanted side effects. The
challenge for both drug and drug delivery
companies is to deliver both existing and emerging
drug technologies in a manner that improves the
current benefits enjoyed by the patients.
The range of techniques for the preparation of
microspheres offers a variety of opportunities to
control aspects of drug administration. There are
various approaches in delivering a therapeutic
substance to the target site in a sustained controlled
release fashion. This approach facilitates the
accurate delivery of small quantity of the potent
drugs, reduced drug concentration at the site other
than the target site and the protection of the labile
compound before and after the administration and
prior to appearance at the site of action. One such
approach is using microspheres as carriers for
drugs2.
Microspheres are defined as “Monolithic sphere or
therapeutic agent distributed throughout the matrix
either as a molecular dispersion of particles” They
can also be defined as structure made up of
continuous phase of one or more miscible polymers
in which drug particles are dispersed at the
molecular or macroscopic level. Microspheres are
the carrier linked drug delivery system in which
particle size is ranges from (1-1000μm) range in
diameter having a core of drug and entirely outer
layers of polymers as coating material18-20
.

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223
Microencapsulation is used to modify and retard
drug release. Due to small particle size of
microspheres, they are widely distributed
throughout the gastrointestinal tract which
improves drug absorption and reduces side effects
due to localized build-up of irritating drugs against
the gastrointestinal mucosa3-4
.
Incorporation of solid, liquid or gases into one or
more polymeric coatings can be done by micro
encapsulation technique. The different methods
used for various microspheres preparation depends
on particle size, route of administration, duration of
drug release and these above characters related to
rpm, method of cross linking, drug of cross linking,
evaporation time, co-precipitation etc5-6
. The
various methods of preparations are Phase
separation coacervation, Spray drying, Solvent
evaporation, Spray coating and pan coating, Freeze
drying, Polymerization, Thermal cross linking.
MATERIALS AND METHODS
Aceclofenac (Yorrow Chem, Products Ltd,
Mumbai), Hydroxy Propyl Methyl Cellulose K4M
(SD Fine Chem Ltd, Mumbai), Eudragit (SD Fine
Chem Ltd, Mumbai), Poly Vinyl Alcohol (SD Fine
Chem Ltd, Mumbai). All the ingredients and
reagents were used Analytical grade.
Table no: 1. Formulation design for Aceclofenac Microspheres
S.No Ingredients ACE 1 ACE 2
1 Aceclofenac 100mg 100mg
2 HPMC K4M 100mg 200mg
3 Eudragit 100mg 200mg
4 Poly Vinyl Alcohol 0.4%(W/V) 0.4%(W/V)
Solvent evaporation method7
Aceclofenac microspheres were prepared by
dissolving the drug in polymer, which was
previously dissolved in the chloroform. The
resulting solution was added to the aqueous phase
containing 0.2% sodium of PVA as an emulsifying
agent and the mixture was then agitated using a
propeller with the rotation speed 500 rpm. The
dispersed drug, Eudragit, HPMC were immediately
transformed into fine droplets, which subsequently
solidified into rigid microspheres due to solvent
evaporation. The particles were collected by
filtration, washed with dematerialized water, and
desiccated at room temperature for 24 hrs.
RESULTS AND DISCUSSION
Results
FTIR8
:
FT-IR studies shown that there were no chemical
interaction between drug and polymers.
Determination of drug entrapments
efficiency 9
Microspheres (100 mg) were suspended in 25 ml of
methanol. After 24 hrs, the solution was filtered
and the filtrate was analyzed for UV-
Spectrophotometer at 275 nm.
SEM
The microparticles were coated uniformly with
gold-palladium by using Sputter coater
(POLARON SC-76430), after fixing the sample in
individual stabs. All samples were randomly
examined for surface morphology of microspheres
by using scanning electron microscope (SEM; LIO-
430).
STANDARD CALBARATION CURVE
100mg of Aceclofenac was dissolved in small
amount of phosphate buffer saline pH
7.4 and
volume was made up to 100ml using phosphate
buffer saline 7.4 from this stock solutions serial
dilutions were done to obtain solutions in the
concentration ranging from 100-1.0-10amg/ml. The
absorbance of solutions were measured at 275nm
Using UV-Visible Spectrophotometer. A graph of
concentration vs absorbance was plotted.
In vitro dissolution studies
Shaking flask method 10
Drug loaded microspheres equivalent to 100mg of
drug were weighted and transferred into 250ml
conical flask. To the 100ml of 7.4PH phosphate
buffer saline was added, then the flask were kept in
a metabolic shaker and shaker was adjusted to 50
horizontal shaker per minute at 37±0.5C. 1ml of the

Yadagiri Phalguna et al / Int. J. of Pharmacy and Analytical Research Vol-3(2) 2014 [222-227]
224
drug releasing media was withdrawn at various
time interval of 30min,1,2,3,4,5,6,7,8,9 , 10 and 12
hours and replaced by the same volume of
phosphate buffer saline. These samples were
filtered through 0.45 m membrane filter. The
filtrate was diluted suitably. The drug was estimate
in each batch by UV-Visible Spectrophotometer at
275 nm.
Discussion
Percentage of entrapment
The percentage of entrapment was determined for
all the batches, the results were shown according to
formulation.
The encapsulation efficiency was found in the
range of 57.35%, 70.35% for AFC-1 and AFC-2
respectively.
SEM Studies
The microspheres were found to be discrete,
spherical and free flowing. The nature of the
microspheres indicates that the microspheres were
multinucleated, monolithic type.
Fig no: 1(a)SEM of Ace 1:2 ratio 500x Fig no: 1(b) SEM of Ace 1:2 ratio 750x
Table no: 2. Absorbance of ACE Fig no: 2 Standard curve of ACE
y = 0.0517x + 0.0033
R² = 0.9987
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0 2 4 6 8 10
Absorbance
Concentration
Standard graph of ACESl. No Concentration Absorbance
(µg/ml)
0 0 0
1 1 0.0581
2 2 0.105
3 3 0.165
4 4 0.201
5 5 0.264
6 6 0.32
7 7 0.362
8 8 0.415

225
Table no: 3. Invitro release profile of microspheres of Ace-1
TIME
(hours)
Absorbance Concentration
(mcg/ml)
% Drug
release
Cumulative
% drug release
0.5 0.453 8.7251 8.7251 8.7251
1 0.721 13.9493 13.9493 14.0366
2 1.086 21.0643 21.0643 21.291
3 1.493 28.9981 28.9981 29.4355
4 1.925 37.4191 37.4191 38.1465
5 2.263 44.0078 44.0078 45.1094
6 2.582 50.2261 50.2261 51.7677
7 2.965 57.692 57.692 59.7359
8 3.22 62.6628 62.6628 65.2836
9 3.642 70.8889 70.8889 74.1363
10 3.973 77.3411 77.3411 81.2974
11 4.265 83.0331 83.0331 87.7628
12 4.567 88.9201 88.9201 94.4802
Table no: 4. Invitro release profile of microspheres of ACE-2
Time
(hours)
Absorbance Concentration
(mcg/ml)
% drug release Cumulative
% drug release
0.5 0.291 5.5673 5.5673 5.5673
1 0.634 12.2534 12.2534 12.3091
2 1.032 20.0117 20.0117 20.1899
3 1.395 27.0877 27.0877 27.466
4 1.821 35.3918 35.3918 36.041
5 2.169 42.1754 42.1754 43.1785
6 2.456 47.77 47.77 49.1949
7 2.835 55.1579 55.1579 57.0605
8 3.113 60.577 60.577 63.0312
9 3.571 69.5049 69.5049 72.5648
10 3.887 75.6647 75.6647 79.4197
11 4.201 81.7856 81.7856 86.2972
12 4.328 84.2612 84.2612 89.5907
Fig no: 3. Invitro graphs of Ace-1, Ace-2
0
50
100
0 5 10 15
Cum%drugrelease
Time in hrs
Invitro graphs of Ace-1, Ace-2
Ace-1
Ace-2

Yadagiri Phalguna et al / Int. J. of Pharmacy and Analytical Research Vol-3(2) 2014 [222-227]
226
Fig no: 4. FTIR Graph of Aceclofenac Pure Drug
Fig no: 5. FTIR Graph of HPMC
Fig no: 6. FTIR Graph of Eudragit
CONCLUSION
In the present study a satisfactory attempt was
made to develop microparticulate drug delivery
system of aceclofenac with improved
bioavailability. From the experiment results it can
be concluded that HPMC, Eudragit polymer is a
suitable carrier for the preparation of microspheres
of Aceclofenac, Particle size analysis reveals that
the microspheres were in the range and all the
formulations showed surface characters, Invitro
studies showed that ACE 1 shows 94.48% ACE2
shows 89.59%. So ACE2 shows sustained release
activity, ACE2 formulation may be reduce the
adverse effect of Aceclofenac.
3907.958 95.623
3857.671 67.6793633.405 0.000
3318.099 150.428
3282.567 0.000
3027.813 214.3922970.569 174.966
2936.735 243.102
2862.986 69.858
2821.251 0.2622681.082 118.3032584.839 34.495
2514.701 -0.1362478.069 73.474
2446.122 10.1262352.004 55.1362307.308 39.581
2208.827 0.000
2080.172 0.000
1920.364 27.9591845.989 73.550
1768.483 465.341
1713.747 33.917
1588.958 99.606
1503.767 267.783
1451.933 0.000
1344.332 362.792
1290.125 76.010
1255.081 347.961
1149.148 392.701
1100.697 112.823
1055.901 426.380
964.749 355.006
926.964 137.040
898.457 280.887
856.121 356.724
748.890 117.183
716.876 124.728665.222 344.896625.099 0.000
584.568 92.337
537.685 79.177
512.407 206.060
479.659 290.675
451.461 350.949
aceclofenac(3)
3500 3000 2500 2000 1500 1000 500
100
90
80
70
60
50
40
30
20
Wavenumber
%Transmittance

227
ACKNOWLEDGEMENTS
The authors are grateful to the Jyothismathi college of pharmacy, Thurkapally(v), Sharmeerpet(M),
R.R-Dist. for providing research facilities.
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Formulation and Evaluation of Microspheres Containing Aceclofenac