BiopharmJournal.
2015,1(2),7180
RESEARCH ARTICLE
OPTIMIZATION OF POLYMERS IN PIROXICAM OCUSERT: IN-VITRO AND IN-
VIVO STUDY
Medha Seth1*, Sailedra Kumar Sahoo2, Nihar Ranjan Pani2
1Gayatri College of Pharmacy, Jamadarpali, Sambalpur, Odisha
2AurosriInsitute of Pharmaceutical Education and Reearch, Jagatpur, Cuttack, Odisha
[Received on: 25th June, 2015 Accepted on: 16nd July, 2015
ABSTRACT
An attempt has been made for the selectionof best
suitable polymer and their concentration for the
preparation of Piroxicambio-adhesive ocusert and
optimization by 3 factorial design to control the
release of drug, reduction of dosing frequency,
increase contact time, improving patient compliance
and enhancement of bioavailability. Ocusert of
piroxicam were formulated by the solvent casting
method and the concentration of polymers such as
polyvinyl alcohol (PVA) and HPMC E5LV was
optimized. Ocusert films were subjected for
investigation of their physicochemical properties; in
vitro and in vivo drug release characteristics. The
formulation containing 0.422 mg of HPMC-E5LV,
0.528 mg of PVA, 0.211 mg of drug and 0.211 mg of
polyethylene glycol- 400, was found to be suitable
for sustained release dosage form with a good
release pattern of drug up to 24 hr. This is further
confirmed by the results obtained from in vivo
studies with high degree of in vitro - in vivo
correlation.
Key words: Ocusert, HPMC, PVA, in vitro-in
vivo correlation, piroxicam
----------------------------------
* Corresponding author
Mobile: +919778784942
E-mail:seth.medha25@gmail.com
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ISSN:24541397
Published on: 28th July, 2015]
1. INTRODUCTION
Continuous precorneal elimination is the major
cause of poor bioavailability of traditional topical
ophthalmic formulations.Frequent instillations of
drug for optimal therapeutic level lead to poor
patient compliance and, drug level in the tear film is
pulsed with an initial period of overdosing and long
period of under dosing (Gilhotra et al., 2009; Hecht,
1995 and Maurice, 1987). Novel ophthalmic drug
delivery systems have been developed to achieve a
better bioavailability of drugs. Application of active
ophthalmic drugs is limited due to their very low
water solubility (Grass and Robinson, 1984).These
problems can be addressed by the development of
ocular drug delivery systems (ODDS) having higher
bioavailability and reduced side effects of potent
drugs.Recent ODDS include: ocular inserts, corneal
shields, and contact lenses that provide controlled
delivery of drug to the eye (Gurtler and Gurny,
1995; Saettone, et al., 1984 and Chien, 1982). The
advantages of ophthalmic inserts over conventional
dosage forms are increased ocular residence; slow
and constant rate of drug release; accurate dosing;
exclusion of preservativesand long shelf life. The use
of ocular inserts (Ocusert) reduces systemic
absorption, which occurs freely with eye drops. The
Low frequency of administration ensures better
patient compliance and least incidence of side effects
(Grass and Robinson, 1984; Chien, 1982 and Lee,
1990). Despite all these advantages, ocular inserts
have disadvantage like foreign body sensation; move
around on the ocular surface causing irritation and
might be easily lost due to un appropriate muco-
adhesive properties and, occasional blurring of
vision due to erosion of soluble inserts into smaller
pieces (Weyenberg et al.,2004 and Sasakia et
al.,2003). It has been attempted to further enhance
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the drug bioavailability and control the drug release
from ocuserts by formulating bio-adhesive ocular
insert by selecting appropriate polymer
concentration.In this study, the concentration of two
polymers such as hydroxyl propyl methyl cellulose
(HPMC E5LV) and polyvinyl alcohol (PVA) are
optimized through 32 factorial design. The design
has two factors, each at three levels i.e. low,
intermediate and high level.
Piroxicam, a biopharmaceutical classification system,
type II (low aqueous solubility, high permeability)
drug (Amidon et al.,1995)selected as model drug in
current work. It is a non-steroidal anti-inflammatory
drug, is a beneficial alternative used effectively in the
treatment and management of postoperative pain
with improved patient compliance
(Gieldanowski,1988). Previously, piroxicam ocular
nanoparticles and microspheres have been
formulated and reported potential dosage forms in
the treatment of postoperative pain, as compared to
piroxicam eye drop (Giunchedi et al.,1999; Sultana,
2002)
polymers such as HPMC E5LVand PVAas shown in
Table 1. PEG 400 was used as plasticizer. Initially,
plasticizers and polymers were dissolved in water to
form a clear solution and was kept at room
temperature for 24 hr. Piroxicam was added into this
polymer-plasticizer solution under mild agitation till
it dissolved. The polymer-plasticizer-drug solution
was poured on the mercury placed in glass
petridishes of 37.5cm diameter. The solvent (water)
was allowed to evaporate for 2448 h at 40-50 0C.
The petridish were covered with inverted funnel
plugged with cotton in the stem to ensure slow
evaporation of solvent. The petridish were covered
with inverted funnel plugged with cotton in the stem
to ensure slow evaporation of organic solvent. The
evaporation leaves HPMC E5LV-PVA-drug patches.
Circular inserts of 8 mm diameter were cut from the
resulting patches with a cork borer.
Table 1. Factorial design and formulae of
piroxicamocusert

In the present study, the Ocusert of piroxicam is

Ingredients in mg/Ocusert
developed and optimized using bio-adhessive Formu
A* B* PEG-
polymers, with an aim to control the release of drug, Lation Drug Water
(HPMC) (PVA) 400
reduced dosing frequency, and enhanceocular
F-1 0.317(-1) 0.317 (-1) 0.211 0.211 Q.S
bioavailability of drug.
F-2 0.317(-1) 0.422 (0) 0.211 0.211 Q.S
2. MATERIALS AND METHODS F-3 0.317(-1) 0.528(+1) 0.211 0.211 Q.S
2.1. Materials F-4 0.422 (0) 0.317(-1) 0.211 0.211 Q.S
F-5 0.422 (0) 0.422 (0) 0.211 0.211 Q.S
Piroxicam was obtained as gift samples from Naxpar
F-6 0.422 (0) 0.528(+1) 0.211 0.211 Q.S
Lab Pvt. Ltd, Silvasa, India. HPMC E5LV, PVA,
Disodium hydrogen phosphate, Mercury, Potassium F-7 0.528(+1) 0.317 (-1) 0.211 0.211 Q.S
dihydrogen phosphate, Sodium chloride, Calcium F-8 0.528(+1) 0.422 (0) 0.211 0.211 Q.S
chloride dehydrate, Aluminium chloride, sodium F-9 0.528(+1) 0.528(+1) 0.211 0.211 Q.S
hydroxide and acetic acid were procured from *Coded value is in bracket; Q.S, Quantity sufficient
LobaChemie. Mumbai, India. Poly ethylene glycol-
2.2.2. Physical appearance, thickness and
400 was purchased from Ranbaxy Fine-Chem. Ltd.,
weight variation
Mumbai, India and Perchloric acid was purchased
from S.D. Fine Chemical Ltd., Mumbai, India. All formulated ocular inserts were visually inspected
for color and smoothness.Thickness of the inserts
2.2. Methods
was measured using micrometer screw gauge.For
2.2.1. Formulation of ocular insert weight variation study, six inserts of each
Ocular inserts containing Piroxicam were prepared formulation were weighed individually on electronic
weighing balance. Averageweight as well as standard
by solvent casting method using varying ratios of

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BiopharmJournal.2015,1(2),7180
deviation of inserts was calculated.
2.2.3.Surface pH Determination
The surface pH of ocusert was determined by agar
plate method (Alanazi et al., 2007; Mishra and
Gilhotra, 2008).The agar plate was prepared by
dissolving 2% (w/v) agar in warm simulated tear
fluid (containing sodium chloride of 0.670 g, sodium
bicarbonate of 0.200 g, calcium chloride of 0.008 g,
and purified water q. s. 100 g under stirring to get
pH 7.4) and then pouring the solution into a
petridish till gelling is occurred at room temperature.
On the prepared agar plate, ocuserts were left to
swell for 5 hr. Then the pH of the wet surface of
soaking ocusert was measured by placing the
electrode in contact with the surface of the insert.
2.2.4.Drug Content
The drug contents were determined by assaying the
individual ocuserts. Each ocusert was dissolved in
5ml dimethylsulfoxide (DMSO) in a 5ml volumetric
flask to make a suspension.The suspension so
obtained was filtered (Whatman filter paper 42, pore
size 2.5 m, Whatman International, Maidstone,
UK).From the above solution,0.5ml was withdrawn
and diluted with simulated tear fluid, pH 7.4 and was
assayed spectrophotometrically at 353 nm. (Double
beam UV-VIS Spectrophotometer, Schimadzu,
Japan)
2.2.5. Tensile Strength, Elastic modulus and
Elongation at break.
An ocusert with good tensile strength and percent
longation would resist tearing due to stressgenerated
by the blinking action of the eye. The tensile
strength and percent elongation at break of film was
determined with a laboratory designed pulley
(Alanazi et al., 2007 and Gevariya et al., 2009). The
sensitivity of the machine was 1 mg to 600kg. It
consists of two load cell grips. Till the film breaks,
the force on the lower one was gradually applied.The
tensile strength of the film was taken directly from
the dial reading in kilogram. The tensile strength,
elastic modulus and elongation at break were
calculated as follows.
Tensile Strength (g/mm2) = Break force(g)/ Cross-
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section Area of the sample(mm2) (1)
Elastic modulus = (Tensile Strength)[(Insert length
after elongation)/(Original Insert length)](2)
Elongation at break (%) = [increase in length at
break point(cm)]/[original Length(cm)100](3)
2.2.6.Swelling Behavior
Swelling of the polymer depends on the
concentration of the polymer, ionic strength, and the
presence of water. Initial weight of insert was taken
to determine the swelling index of prepared ocusert,
and then placed in a beaker containing 4ml distilled
water (Gevariya et al., 2009). At regular interval of
time (every 10 min), the film were removed and the
excess water on their surface was removed using a
blotting paper and then again weighed. The
procedure was continued till there was no increase in
the weight. The swelling index was then calculated
by dividing the increase in weight by the initial
weight and was expressed as percentage.
2.2.7. Percentage of moisture loss
Ocuserts were weighed and kept in desiccators
containing 2gm of anhydrous calcium chloride. After
three days, inserts were taken out and reweighed
(Dhanaraju et al., 2002). Percentage moisture loss
was calculated using the equation:
% Moisture Loss = [(Initial weight - Final weight) /
Initial weight] 100 (4)
2.2.8. Percentage of moisture absorbed
Ocular inserts were weighed and kept in desiccators
containing aluminum chloride and 79.5 % w/w
moisture was maintained (Dhanaraju et al.,
2002).After three days inserts were taken out and
reweighed. Percentage moisture absorbed was
calculated using the equation:
% Moisture Absorbed = [(Final weight - Initial
weight) / Final weight] 100 (5)
2.2.9. Folding endurance
The folding endurance is expressed as the number
of folds either to break the specimen or to develop
visible cracks (Harish et al., 2009 and Gevariya et al.,
2009).This test is important to access the ability of
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ocusert film to withstand folding and brittleness.
The film was folded in center(between the fingers
and the thumb) and then opened, it was one folding.
The process was repeated till the insert shows
breakage or cracks in center of insert. The total
folding operations were named as folding endurance
value.
2.2.10.Ocular irritation study
The ocular irritation study was performed in four
albino rabbits after getting prior approval from
institutional animal ethics committee of Gayatri
College of Pharmacy, Sambalpur, Odisha, India.
Rabbits were used in the study and were examined
precisely for any preexisting ocular damage.
Sterilization of ocusert was done by placing films
under UV light in UV germicidal chamber, exposing
both sides for 15 min at a 10 cm height from
UVlamp (Doijad et al., 2006).The sterile selected
ocusert was placed in one eye of each animal by
gently pulling the lower eyelid away from the eye
ball. The lids were then being held together for one
second and animal is released. The other eye,
remaining untreated was served as the control. The
eyes of each rabbits were examined at 12, 24, 36, and
48hrs after treatment for irritation, inflammation etc
by naked eye or by means of a pen torch. The test
may consider as positive if three or more animal
exhibit positive reactions at any observation period
(Dandagi et al., 2004).
2.2.11. In- vitro diffusion studies
An in vitro open flow through KC cell, designed
for release studies as described. The semipermeable
membrane of hen egg acts as corneal epithelium.The
entire surface of the membrane was in contact with
receptor compartment containing 25ml of simulated
tear fluid, pH 7.4. An ophthalmic insert was placed
inside the donor compartment. With the help of a
magnetic stirrer thecontent of the receptor
compartment was stirred continuously and
temperature was maintained at 37 0.5 C. At
regular intervals, the diffusion fluid of 1ml was
withdrawn from the receptor compartment and
diluted up to 5ml and replaced with fresh simulated
tear fluid solution to analyze drug content at 354 nm
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usingsimulated tear fluid as blank, using a UV/Vis
double-beam spectrophotometer. Cumulative
percentage of the drug release was calculated using
an equation obtained from a standard curve.
2.2.12In- vivo diffusion studies
The in vivo study was examined on male albino
rabbits, weighing about 1.5 kg and 2kg months old.
They were housed in cages under controlled
conditions of temperature (272oC) and light. They
were fed with standard laboratory diet; and water
was provided. The ophthalmic inserts (n=4) were
placed in the cul-de-sac of the right eye and similarly
a blank film was placed in the left eye to serve as
control. At regular time intervals, the ocular inserts
were removed carefully and analyzed for the drug
content spectrophotometrically at 354.0 nm.
Whenever an insert was removed from the rabbits
eye a new one replaced it. The drug content
obtained was subtracted from the initial drug
content in the ocusert, to give the amount of drug
released in the rabbits eye (Gevariya et al., 2009;
Abilash et al., 2005).
2.2.13 Kinetics of drug release
The drug release kinetics is the useful tools to
correlate the in vitro and in vivo drug responses by
comparing the results of pharmacokinetics with
dissolution profiles of ocuserts. Different
mathematical models i.e., zero order, first order and
Higuchi equations were applied for describing the
kinetics of the drug release process from ocusert,
and the most suited being the one which fitted best
the experimental results.The in vitro drug release
data obtained from in-vitro diffusion study were
used to calculate the correlation coefficient (R) value
between cumulative amount of drug released and
time for zero order, log cumulative percentage of
drug remaining and time for first order and
cumulative percentage of drug released and square
root of time for Higuchis model . The best fit
model was considered to that one which had
maximum R value (~1) (Acharya et al., 2014).
2.2.14. Mechanism of drug release
The commonly adopted model for understanding
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release of drug from hydrophilic matrix is a simple
exponential equation known as KorsmeyerPeppas
equation.
Mt/ M = Kptn (6)
Where Mtis the amount of drug release at time t, M
is the total amount of drug release after an infinite
time, Kp is a constant related to the structural and
geometric properties of the drug delivery system and
n is the release exponent related to the mechanism
of release. Peppas used this n value in order to
characterize different release mechanisms. The n
value was obtained from the slope of a plot of
logMt/Mversus log time. If the nvalue is 0.5 or
less, the release mechanism follows Fickian
diffusion,and higher values 0.5 < n < 1 for mass
transfer follow a non-Fickianmodel (anomalous
transport). The model follows zero-order
drugrelease and case-II transport if the n value is
equal to 1.For the values of n higher than 1, the
mechanism of drug release is regarded assuper case-
II transport (Acharya et al., 2014 and, Pani and
Nath, 2014).
2.2.15. Experimental design, statistical analysis
and optimization
A 3 randomized full factorial design was used to
optimize the variables in the present study. In this
design, two factors were evaluated, each at three
levels and experimental trials were performed at all 9
possible combinations (Acharya et al., 2014 and,
Pani and Nath, 2010). The different percentage of
HPMC E5LV and PVA, were selected as
independent variables. Thetimes required for 10% of
drug release (t10), 50% of drug release (t50),90% of
drug release (t90)were selected as dependent
variables. Data obtained from all formulations were
analyzedusing Design Expert software (Stat-Ease-7,
Minneapolis, USA) and used to generate the study
designand the response surface plots. Polynomial
models, including linear, interaction and quadratic
termswere generated for all the variables using the
software.The best fitting model was selected based
on comparisons of several statistical parameters,
including the coefficient of variation(CV), regression
coefficient (R) and adjusted regression
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coefficient(adjusted R) provided by Design Expert
software.In addition, analysis of variance (ANOVA)
was used to identify significant effects offactors on
variable regression coefficients. The F test and P
valueswere also calculated using the software.The
relationship between the factors and response
variables was further elucidated using response
surface plots. These plots are useful to study the
effects of various independent variables on the
dependent variables at a given time and to predict
the responses of dependent variables at intermediate
levels of independent variables.Subsequently, a
numerical optimization technique using the
desirability approach and a graphical optimization
technique using overlay plots were used to generate
new formulations with the desired responses.
2.2.16.Statistical analysis
Statistical optimization was performed using Design-
Expert software. All measured data are expressed as
mean standard deviation (S.D.).
3. RESULT AND DISCUSSION
3.1. Formulation of Ocusert
The objective of present investigation was preparing
a controlled release bioadhesive ocular insert of
piroxicam using HPMC E5LV and PVA as
bioadhesive polymers. PEG was employed as a
plasticizer in the preparation to get inserts/films
with good elasticity. Solvent casting procedure was
followed to prepare formulations that resulted in the
preparation of uniform drug-polymeric ocuserts.
The drug was dissolved in the polymeric solutions
prior to casting. The concentration of polymers is
very important in the preparation of the polymer
matrix. The solution of the polymers was kept at
room temperature for 24 hr in order to enhance
inter diffusion of polymer particles upon drying,
polymer solutions were converted into drug polymer
inserts/films. Various research groups have studied
the mechanism of film formation from polymer
dispersions. The film formation occurs in three
stages: (a) evaporation of casting solvent and
subsequent concentration of polymer particles; (b)
deformation and coalescence of polymer particles;
and (c) further fusion by inter diffusion of polymeric
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molecules of adjacent polymer particles.

Table 2. Evaluation of physical parameters of piroxicamocusert
Parameter F-1 F-2 F-3 F-4 F-5 F-6 F-7 F-8 F-9

Drug content 101.20 98.67 100.08 104.67 103.33 106.33 101.08 105.83 102.07
(% w/w) 1.38 1.12 1.09 1.11 1.03 0.98 0.72 0.64 1.95

Weight (mg) 13.14 17.22 19.32 21.21 22.82 24.08 19.76 20.80 25.45
0.21 0.16 0.09 0.11 0.21 0.20 0.26 0.18 0.21

Thickness 0.18 0.25 0.32 0.37 0.38 0.39 0.41 0.33 0.31
(mm) 0.03 0.02 0.22 0.04 0.07 0.05 0.05 0.08 0.06

Tensile strength 1.28 1.28 1.36 1.28 1.22 1.34 1.34 1.28 1.38
(g/mm2) 0.15 0.34 0.11 0.76 0.44 0.16 0.19 0.98 1.12

Elastic modulus 1.23 1.20 1.33 1.18 1.19 1.28 1.21 1.25 1.35
(g/mm2) 1.09 0.77 1.98 0.54 0.61 0.81 0.08 0.50 0.99

Elongation at 4.44 6.67 2.22 8.89 2.22 4.44 11.01 2.22 2.22
break (% w/w) 0.36 0.87 0.53 0.06 0.91 0.05 1.61 1.01 1.07

*Value expressed in Mean standard deviation

3.2 Physiochemical Evaluation The drug content was consistent in all batches and
varied from 98.67 % to 106.33% and shown in
The physical state of the drug in the dried polymer is
table2. Tensile testing gives an indication of the
dependent on the solubility of the drug in the
strengthand elasticity of the insert, reflected by the
polymer. The success of the film formation method
parameters tensile strength (TS), elastic modulus
is further evident from the fact that the prepared
(EM) and elongation at break (E/B). A soft and
inserts were translucent, colorlessand smooth in
weak insert is characterized by a low TS, EM, and
texture; uniform in appearance, thickness, and
E/B. A hard and brittle insert is defined by a
weight; and showed no visiblecrack or imperfection.
moderate TS, high EM, and low E/B. A soft and
Each ocular insert had an area of approximately 77
tough insert is characterized by moderate TS, low
mm2. The insert had a thickness varying from
EM, and high E/B, whereas a hard and tough insert
0.180.00, 0.250.02, 0.310.22, 0.370.04,
is characterized by a high TS, EM, and E/B.Hence,
0.370.07, 0.390.05, 0.400.04, 0.330.08,
it is suggested that a suitable bioadhesive ocular
0.310.06mm and weight varying from 13.10.201,
insert should have a relatively moderate TS, E/B,
17.20.136, 19.30.089, 21.20.109, 22.80.213,
and strain but a low EM.In the present study,
24.080.209, 19.760.265, 20.80.187, 25.450.207
bioadhesive polymers cast from aqueous solvent
mg (shown in table 2). It was found that the
werePVA and HPMC E5LV which is widely
thickness and weight of the insertsincreased with
accepted in the preparationof ocular inserts. Table 2
increasing total polymer concentration. The inserts
shows the mechanical properties of the prepared
were found to possess uniform weight and thickness
Piroxicam ocular inserts. Addition of PEG as a
within the batch. Surface pH was within the range of
plasticizer gave inserts of good mechanical
7.0 to 8.0. This shows that prepared inserts were
propertiesas evident from the satisfactory elongation
neutral pH and would not cause irritation in the eye.
at break parameters for all inserts. PEG, as a

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BiopharmJournal.2015,1(2),7180 ISSN:24541397

plasticizer, allows the polymer-drug matrix administration of formulation,the rabbits eyes were
molecules to move more freely resulting in an inspected visually at specific time intervals. There
increase in the flexibility of the inserts. The order of was no sign of redness and continuous blinking of
tensile strength of the inserts were F-9 > F-3> F-6= eyes was observed. No ocular damage or abnormal
F-7> F-1=F-2=F-8>F-5 and elastic modulus was clinical sign to cornea, iris and conjunctiva were
ranges between1.23 1.09 to 1.35 0.99gm/mm visible. Thus the formulation was nonirritant to
(shown in table2). For ocular application,soft and rabbit eye.
tough inserts are preferred as these can withstandthe 70
continuous wear and tear of frequent blinking of the F1 F2 F3
eye without irritating the ocular tissue and enhance 60 F4 F5 F6

Cumulative%ofdrugrelease
patient compliance. F7 F8 F9
50
3.3. Swelling behavior
40
The swelling behavior of the polymer was reported
to be crucial for its bioadhesive character. The 30
adhesion occurs shortly after the beginning of 20
swelling but the bond formed is not very strong. The
swelling of drug loaded films of size 2cm observed 10
in 4ml of water. The data for increase weight due to
0
swelling were given in figure1. As concentration of
0 2 4 6 8
HPMC E5LV increase, the swelling index of the Time(hr)
films also increases.
Figure 2. In vitro drug release study of
90 F1 F2 F3 piroxicamocuserts
F4 F5 F6
80 F7 F8 F9 3.5.In-vitro release study
Increaseinweightofocusert(%)

70 The in vitro cumulative amount of drug release from

60 piroxicamocuserts is presented in figure 2.The
figure-2 indicates that the drug release I controlled
50
manner from prepared ocuserts i.e. less than 50 %
40 w/w within 7 hrs except F-3. For the determination
30 of the release mechanism of drug, the in vitro release
data were fitted to zero-order, first-order and
20
diffusion-controlled release mechanism according to
10 the simplified Higuchi model, Korsmeyer-Peppas
0 model. The preference of a certain release
0 10 20 30 40 mechanism was based on the correlation coefficient
Time(min)
(r) for the parameters studied, where the highest
correlation coefficient is preferred for the selection
Figure 1. Results of swelling behavior study of of the mechanism of release.Successive evidence of
piroxicamocusert the relative validity of diffusion and zero order
3.4. Eye irritation study models was obtained by further analyzing the data
using Korsmeyer-Peppasequation.The mathematical
This study was performed to determine whether the
treatment of the in vitro release data of Piroxicam
formulation cause irritation and pain, after its
ocular inserts resulted that the drug release from the
administration.This study was performed in rabbits
matrix iscontrolled by both coupling erosion and
using sterilized optimized formulation F-6. After
diffusion mechanism as n value was within 0.5 to 1.

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BiopharmJournal.2015,1(2),7180
3.6. In vivo release
The sterilized optimized Formulation (F-6) subjected
to in vivo studies in thealbino rabbit eye. The drug
release at the end of the 8 hr was found to be
93.59% and the releasecharacteristics were similar to
those obtained fromin vitro studies.
3.7.In vitro-In vivo correlation
The in vitro and in vivo release profiles of the insert,
(F-6) containing Piroxicam indicated that the release
of drug was not significantlydifference from the
amounts of drug released at the end of 24 h. The
difference between the Piroxicam released from
ocular inserts during in vitro and in vivo studies for
formulation (F-6) was found to beinsignificant
(p>0.05, F-value is less than table value). Polymeric
ocular inserts appeared to be devoid of any irritant
effect on cornea, iris, and conjunctiva up to 24 h
after application, which probably suggest its
suitability for ophthalmic drug delivery. An attempt
was made to correlate invitro and in vivo release
(Figure 3). A linearcorrelation was obtained as it was
evident fromthe regression value of 0.992 for(F-6).
50
45
PercentageofdrugAbsorbed
40 R=0.992
35
30
25
20
15
10
5
0
0 50
Percentageofdrugdiffused
Figure 3. In vitro in vivo Correlation study of
piroxicamocusert (F-6)
3.8. Analysis of data and optimization of design
By using Design Expert software,
obtained from the experiment were
analyzed for response variables. A
formulations were proposed by the
design for two independent variables:
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HPMC H5LV (A) and amount of PVA (B), which
were varied at two different levels (high and
low).The effects of these independent variables on
t10, t50 and t90were investigated as optimization
response parameters in the current investigation.
The software provided suitable polynomial model
equations involving individual main factors and
interaction factors after fitting these data.The
optimized model equations relating Y1 (t10), Y2 (t50)
and Y3 (t90) as responses are given in Eq .(1),(2) and
(3) respectively.
Y1 = t10= 2.24 +0.45*A - 0.65*B - 0.099*A*B +
0.03*A (7)
Y2 = t50= 11.86 + 3.67*A- 3.19*B - 0.42A*B+
0.94A (8)
Y3 = t90 = 21.82 +7.67*A-5.69 *B-
0.63*A*B+2.34*A (9)
In all above cases i.e.Y1 (t10), Y2 (t50) and Y3 (t90), the
+ve coefficient of A and ve coefficient of B are
observed. It signifies that the concentration of factor
A (HPMC H5LV)is directly proportional to t10, t50
and t90; the concentration of factor B (PVA)
inversely proportional to t10, t50 and t90. The 3D plot
(Figure 4.a, b and c) showed that a downward trend
of wire mesh were depicted at higher level(+1) and
the upward trend at lower levelof (-1) of the
concentration of A and B. It is further support the
predicted information from optimized equations.
a)
100
the results
statistically
total nine
32 factorial
amount of
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BiopharmJournal.2015,1(2),7180
b)
c)
Figure 4. 3-dimenssional figure of a) t10, b) t50
and c) t90
4. CONCLUSION
The concentration of HPMC and PVA was
optimized for the preparation of controlled release
ocuserts of piroxicamby solvent casting method
through 32 factorial design. The formulation F-6
(containing 0.422 mg of HPMC-E5LV, 0.528 mg of
PVA, 0.211 mg of drug and 0.211 mg of PEG 400)
was found to be suitable for sustained release dosage
form with a good release pattern of the drug for up
to 24 hr. This is further confirmed by the results
obtained from in vivo studies, with high degree of in
vitro and in vivo correlation. Therefore it was
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ISSN:24541397
concluded that formulation F-6 is the best
formulation amongst all formulation and can be
used effectively in the treatment and management of
post- operative pain with improved patient
compliance.
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