Int. J. Drug Res. Tech. 2013, Vol.

3 (4), 88-95 ISSN 2277 - 1506

International Journal of Drug Research and Technology

Available online at http://www.ijdrt.com
Original Research Paper
FORMULATION AND EVALUATION OF OCULAR INSERTS OF
ACYCLOVIR
Sharma Reshu1*, Goswami Laxmi and Kothiyal Preeti
Division of Pharmaceutical Sciences, S.G.R.R.I.T.S,
Patel Nagar, Dehradun-248001,
Uttarakhand, India
ABSTRACT
Acyclovir, an antiviral is effective against human Herpes Simplex viruses, commercially available as a 3
% w/w eye ointment to be applied 5 times a day in the eye. The poor therapeutic response exhibited by
conventional ophthalmic ointments due to rapid precorneal elimination of the drug may be overcome by
the use of an ocusert inserted in the cul-de-sac of lower eye lid. Inserts containing Acyclovir were
prepared by using solvent casting method. Drug reservoir and rate controlling membrane were prepared
using different hydrophilic and hydrophobic polymers respectively with Poly ethylene glycol 400 as the
plasticizer. DSC and IR spectral studies were performed to confirm the interaction of drug and polymers
in formulation. The ocusert were evaluated for their physic chemical properties, mechanical properties
and in-vitro release characteristics. The developed formulation was stable, sterile and non-irritant.
Keywords: Acyclovir, Ocusert, diffusion, Hydroxypropyl methylcellulose, Polyvinyl alcohol.
INTRODUCTION
The physiological constraints imposed by the improved ocular therapy by ophthalmic
protective mechanisms of the eye lead to low inserts. Acyclovir is a polar drug with short
absorption of drugs and a short duration of the plasma half life of 2-3 h7, therefore 4-5 times
therapeutic effect on ocular drug delivery. Upon application is required when administered as
instillation of the eye drops only 1–10% of the ophthalmic ointment. Also, about 95% of the
drug is bioavailable while the rest is drained out drug is drained out due to high tear turn-over via
of the eye through lacrimal secretions.1 To nasolacrimal drainage leading to ineffective
overcome this problem various approaches have therapy. Several approaches have been used to
been reported, such as ointments, inserts and improve ocular bioavailability of acyclovir.
aqueous gels, to increase the ocular residence In the present work an ocular insert of acyclovir
time of topically applied medication. Controlled is prepared in order to minimize its side effects
drug delivery to the eye offer several advantages on being used as conventional dosage form in
over conventional therapies like drug solutions order to treat periocular disease like Keratitis
or suspensions as eye drops.2,3 Ophthalmic caused by virus. This drug is mainly used to treat
inserts offer many advantages over conventional herpes simplex, herpes zoster, and varicella
dosage forms, like increased ocular residence, zoster viral infections In the present work an
possibility of releasing drugs at a slow and ocular insert of acyclovir is prepared in order to
constant rate, accurate dosing, and exclusion of minimize its side effects on being used as
preservatives, increased shelf life and reduced conventional dosage form in order to treat
systemic absorption.4,5,6 Several reports revealed periocular disease like Keratitis caused by virus.

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 Sharma Reshu et al. International Journal of Drug Research and Technology 2013, Vol. 3 (4), 88-95
This drug is mainly used to treat herpes simplex,
herpes zoster, and varicella zoster viral
infections.8,9
MATERIALS AND METHODS
Acyclovir was provided by Kausikh
Therapeuticals Pvt. Ltd., Chennai. The polymers
HPMC K4M, Polyvinyl alcohol, Eudragit
RL100, Eudragit RS100 were purchased from
Paras pharmachem., Pune. All other ingredients
were of analytical grade.
Preparation of Simulated Tear Fluid
The ingredients for preparing 100 ml of the
simulated (artificial) tear fluid are as follows:
placed in a Teflon coated Petri dish. The solvent
was allowed to evaporate by placing it inside an
oven maintained at 35 ± 2°C, 30 ± 0.5% RH for
24 h. 10,11,12
Preparation of rate controlling films
To prepare the rate controlling films,
hydrophobic polymer (Eudragit RS100/ Eudragit
RL100), along with plasticizer, dibutyl phthalate
were dissolved in ethanol/acetone (80:20)
mixture. The solutions were poured into a glass
ring of 8.9 cm diameter placed in a Teflon coated
Petri plate. The solvent was allowed to
equilibrate at 25 ± 0.5° C, 45 ± 0.5 % RH for 24
h.13,14,15

S.No. Ingredients Quantity Placing rate controlling films around the drug
reservoir and sealing them to obtain ocular
1. Sodium Chloride 0.670 g
inserts
2. Sodium Bi-carbonate 0.200 g Circular shaped ocular inserts were cut out of
3. Calcium Chloride 0.008 g medicated reservoir film with the help of a cork
4. Distilled Water (q. s.) 100 ml borer (special device). These ocular inserts were
placed on a rate-controlling membrane and
Formulation of Ocular Inserts for Controlled another rate controlling membrane was kept over
Delivery it. The two rate controlling membranes
The preparation of ocular inserts involved three containing the reservoir film between them were
steps: placed over a beaker saturated with
Preparation of the drug containing reservoir film ethanol/acetone vapours (60:40) for 1-2 minutes.
of hydrophilic polymers The final ocular inserts consisted of three films;
For preparation of the drug containing reservoir reservoir films containing the drug were
film, polymeric solutions were prepared by sandwiched in between the rate controlling
dissolving hydrophilic polymer (HPMC/PVA), membrane to control the release. Each ocular
along with Acyclovir and poly ethylene glycol insert contained 1mg of the drug. The ocular
400, in doubly distilled water. The solutions inserts were stored in an airtight container under
were poured into a glass ring of 8.9 cm diameter ambient conditions.16,17

Table 1: Formulation: Preparation of Drug Reservoir

Ingredients F1 F2 F3 F4 F5 F6 F7 F8
Acyclovir* 10 10 10 10 10 10 10 10
HPMC K4M* 3 6 _ _ 3 6 _ _
PVA* _ _ 3 6 _ _ 3 6
PEG 400** O.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8
Distilled water** 10 10 10 10 10 10 10 10

*quantity in %,**quantity in ml

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 Sharma Reshu et al. International Journal of Drug Research and Technology 2013, Vol. 3 (4), 88-95
Table 2: Preparation of Rate Controlling Membrane
Ingredients F1 F2 F3 F4 F5 F6 F7 F8
Eudragit 6 3 6 3 _ _ _ _
RS100*
Eudragit _ _ _ _ 6 3 6 3
RL100*
PEG 400** 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8
Acetone** 10 10 10 10 10 10 10 10
*quantity in %, **quantity in ml

without breaking gave the value of folding

INTERACTION STUDIES
Interaction studies were conducted by comparing
pure drug with polymers by IR
Spectrophotometry. Infrared spectra were taken
by using KBr pellet technique using a Perkin
Elmer IR (Spectrum TwoTM)Spectrometer in the
wavelength region of 4000 to 400 cm-1.The
procedure consisted of dispersing a sample (drug
alone and mixture of drug and excepients) in
KBr and compressing into discs by applying a
pressure of 5 tons for 5 mins in a hydraulic press.
The pellet was placed in a light path and the
spectrum was obtained.
EVALUATION OF PREPEARED
FORMULATIONS
The ocuserts were evaluated for thickness,
folding endurance, drug content, surface pH, and
in-vitro diffusion studies.
Uniformity of Thickness
Insert thickness was measured by a Vernier
caliper at five different points on the film. The
mean thickness and standard deviation (SD)
were calculated.
Uniformity of Weight
Five films were taken from each batch and their
individual weights were determined by using
electronic balance.
Folding Endurance
Folding Endurance of the film was determined
by repeatedly folding the inserts at the same
place till it breaks. The ocuserts was folded in
the center, between finger and thumb and then
opened. This was one folding. The number of
times, the film could be folded at the same place
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endurance.18
Uniformity of Drug Content
Uniformity of drug content was determined by
assaying the individual inserts. Three films were
taken from each batch and individually dissolved
or crushed in 5 ml of simulated tear fluid in a
beaker and filter it into the beaker 0.5 ml of the
filtered solution was taken in 20ml beaker and
diluted to 15 ml with simulated tear fluid. The
absorbance of each of these solutions was then
measured on UV-visible spectrophotometer at
254 nm.
Swelling Index
Three films were weighed and placed separately
in beakers containing 4ml of simulated tear fluid.
After a period of 5 minutes, the films were
removed and the excess water on their surface
was removed using a filter paper and then again
weighed till there was no increase in the weight
and then the swelling index was calculated using
the following formula:
% SW = [(WT – WO) / WO] x 100
Where,
%SW = percentage swelling index;
WT = weight of swollen insert after time T;
WO = original weight of insert at zero time;
Percentage Moisture Absorption
Percentage moisture absorption test was carried
out to check the physical stability of the ocusert
at high humid condition. The ocuserts were pre
weighed accurately and kept in desiccators
containing 100 ml of saturated solution of
aluminium chloride. After 72 hours (3 days), the
films were taken out, weighed and percentage
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moisture absorption was calculated by using
formula.19
% MA = [(final weight– initial weight) / initial
weight] x100
Where,
%MA = percentage moisture absorption
Percentage Moisture Loss
This test was carried out to check the integrity of
ocusert at dry condition. The ocuserts were
weighed accurately and kept in a desiccators
containing anhydrous calcium chloride. After 72
hours (3 days), the films were taken out, weighed
and percentage moisture loss was calculated by
using formula.20
% ML = [(initial weight– final weight) / final
weight] x100
Where,
%ML = percentage moisture loss
In-Vitro Diffusion Studies
The in vitro diffusion of drug from the different
ophthalmic insert was studied using the classical
standard cylindrical tube fabricated in the
laboratory. A simple modification of open ended
glass tube was used. The diffusion cell
membrane (pre hydrated cellophane) was tied to
end of open cylinder, which acted as a donor
compartment. An ophthalmic insert was placed
inside this compartment. The diffusion cell
membrane acted as corneal epithelium. The
Figure 1: Calibration Curve of Acyclovir
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entire surface of the membrane was in contact
with the receptor compartment containing 25 ml
of simulated tear fluid in 100 ml beaker. The
content of receptor compartment was stirred
continuously using a magnetic stirrer and
temperature was maintained at 370C±0.50C. At
specific interval of time, 1ml of the sample
solution was withdrawn from the receptor
compartment and replaced with fresh simulated
tear fluid solution. The aliquot was analyzed for
the drug content using UV-VIS
Spectrophotometer at 254 nm after appropriate
dilutions against reference using as simulated
tear fluid as blank.
RESULT
In the present study, an attempt is made to design
polymeric ocular drug delivery system of
acyclovir to overcome the disadvantages
associated with the conventional ophthalmic
dosage forms (eye drops and suspensions), to
achieve long duration of action and to improve
ocular bioavailability. Acyclovir is an antiviral
drug used in treatment of ocular infections. It is
effective against trachoma and conjunctivitis.
The formulated ocuserts were then evaluated for
their average weight variation, thickness, drug
content, in vitro drug release. Here figure 1
shows the calibration curve of acyclovir.
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Interaction studies

Figure 2: FTIR Spectra of acyclovir

Figure 3: FTIR Spectra of Acyclovir + HPMC K4M

Figure 4: FTIR Spectra of Acyclovir + PVP K30

The graph obtained of drug sample was
compared with the graph of Acyclovir given in
IP and Analytical Profile of Drug Substances,
Klaus Florey, vol. 8, Academic Press, London.
The two graphs match with each other it shows
that the drug sample used is pure and stable.
Uniformity of Thickness
Thickness specifications may be set on an
individual product basis. There were no marked
variations in the thickness of ocuserts within
each formulation indicating uniform behaviour
of film throughout the sealing process. The
thickness of the ocuserts of all formulations were
tabled.
Uniformity of Weight
The weight of all the films were found to be in
the range of 5.6-6.0 mg. The uniformity of
weight of the film indicates good distribution of
the drug, polymer and plasticizer. The weight
variations of ocuserts of all formulations were
tabled.
Folding Endurance
Use of less amount of plasticizer was observed to
cause brittleness in the medicated discs, but use

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 Sharma Reshu et al. International Journal of Drug Research and Technology 2013, Vol. 3 (4), 88-95
of greater amount of plasticizer (1ml plasticizer measured for all formulations manually. It was
per 10 ml) displayed little opaqueness and good found in the range of 169.66 ± 2.081 to 188.55 ±
folding endurance. The folding endurance was 3.605.
Table 2: Thickness, weight variation and folding endurance of Acyclovir ocusert
Formulation Code Thickness (mm)** Weight variation (mg) ** Folding endurance *
F1 0.13 ± 0.012 5.6±0.122 85
F2 0.17 ±0.015 5.84±0.167 89
F3 0.15 ± 0.011 5.86±0.151 84
F4 0.16 ± 0.015 5.86±0.151 91
F5 0.17 ± 0.016 5.94±0.167 97
F6 0.17 ± 0.024 5.92±0.130 88
F7 0.18 ± 0.011 6.00±0.158 93
F8 0.19 ± 0.019 6.06±0.167 95
All the values are expressed as mean± S.D., ** n=5, *n=3

Uniformity of Drug Content

Results of the content uniformity test complied showed that the method for the preparation of
with the BP 2005 requirements. These results inserts gave reproducible results.
Table 3: Drug content uniformity of Acyclovir ocuserts
S. No. Formulation code % drug content ± SD
1 F1 94.32 ± 0.209
2 F2 97.77 ± 0.478
3 F3 95.43 ± 0.065
4 F4 98.35 ± 0.230
5 F5 98.36 ± 0.167
6 F6 99.16 ± 0.258
7 F7 96.68 ± 0.183
8 F8 96.04 ± 1.600
All the values are expressed as mean± S.D., *n=3

Table 4: Swelling index of Acyclovir ocusert

S. No. Formulation % swelling index ± SD
1 F1 83.60 ± 0.224
2 F2 92.65 ± 0.801
3 F3 83.51 ± 0.254
4 F4 85.46 ± 0.723
5 F5 91.05 ± 0.862
6 F6 83.61 ± 0.614
7 F7 89.08 ± 0.163
8 F8 91.86 ± 0.697
All the values are expressed as mean± S.D., *n=3

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 moisture loss were high, there was no change in
Percentage Moisture Absorption and
integrity at high humid and dry conditions which
Percentage Moisture Loss
was observed by physical appearance. The
Percentage moisture absorptions were observed
values were calculated and tabled.
from 3% to 10%. Percentage moisture losses
were observed from 6% to 9%. Though the
percentage moisture absorption and percentage
Table 5: Percentage moisture absorption and percentage moisture loss
S. No. Formulation code % Moisture absorption* ± SD % Moisture loss* ± SD
1 F1 3.36 ± 0.020 6.42 ± 0.82
2 F2 9.09 ± 0.880 6.47 ± 0.85
3 F3 10.10 ± 0.075 6.63 ± 0.90
4 F4 4.44 ± 0.780 8.59 ± 0.93
5 F5 5.49 ± 0.820 6.57 ± 0.98
6 F6 5.74 ± 0.810 7.01 ± 0.95
7 F7 9.76 ± 0.810 6.78 ± 0.87
8 F8 7.79 ± 0.919 9.31 ± 0.08
All the values are expressed as mean± S.D., *n=3

In-Vitro Diffusion Studies

In-vitro drug release revealed that 94% of drug through an semi permeable dialysis membrane
released from the formulation F6 containing 4% over an extended period of 8 hours as depicted in
HPMC and 2% Eudragit RL100 in combination figure:

Figure 5: In-vitro drug release of Acyclovir ocusert

The formulation F6 satisfied required
CONCLUSION
pharmaceutical characteristics of ocular inserts
Reservoir type ocular inserts comprising
and was found promising.
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Cite This Article: Sharma, Reshu; Goswami, Laxmi and Kothiyal, Preeti (2013), “Formulation And
Evaluation Of Ocular Inserts Of Acyclovir”, International Journal of Drug Research and
Technology, Vol. 3 (4), 88-95.
Correspondence Author: Sharma Reshu
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