Preparation of In Situ-Forming Ophthalmic Gels of

Ciprofloxacin Hydrochloride for the Treatment

of Bacterial Conjunctivitis: In Vitro and In Vivo Studies
NASEEM A. CHAROO, KANCHAN KOHLI, ASGAR ALI
Department of Pharmaceutics, Faculty of Pharmacy, Hamdard University, New Delhi-110062, India

Received 4 January 2002; revised 4 June 2002; accepted 3 July 2002

ABSTRACT: Sol-to-gel systems of ciprofloxacin hydrochloride were prepared utilizing

the phase transition properties of hydroxy propyl methyl cellulose K 15 M grade (HPMC)
and carbopol 934.The sol-to-gel systems were sterilized by gamma radiation and/or
filtration. The sol-to-gel systems were evaluated for rheological characteristics, in vitro
release behavior, microbial efficacy, in vivo release behavior, and efficacy against induced
bacterial conjunctivitis in rabbits’ eyes. Concentration in aqueous humor was determined
and stability studies were carried out as per the ICH guidelines. The system passed the
test for sterility. The sol-to-gel system exhibited a zero-order drug release pattern over
24 h in in vitro release studies. The drug was active against selected microorganisms
in microbial efficacy studies. Better improvement in artificially induced bacterial
conjunctivitis in rabbits’ eyes was observed in animals treated with the sol-to-gel system
compared with marketed eye drops. Drug concentration in aqueous humor was greater
than the minimum inhibitory concentration (MIC 90) against selected microorganisms.
The shelf-life of the product was >2 years. ß 2003 Wiley-Liss, Inc. and the American
Pharmaceutical Association J Pharm Sci 92:407–413, 2003
Keywords: sol-to-gel system; bacterial conjunctivitis; ciprofloxacin hydrochloride

INTRODUCTION delivery system that promotes prolonged release of

Topical administration or application of antibac-
terial medication to the conjunctival sac is usually
an effective avenue for treating bacterial conjun-
tivitis.1 Ciprofloxacin hydrochloride is very widely
used antibiotic for the treatment of infectious
types of conjunctivitis caused by gram negative
bacteria. It affects bacterial DNA gyrase without
affecting mammalian DNA activity. Because of its
short elimination half-life, it must be instilled as
3–4 drops at least three times a day.2–4
The patient compliance and efficacy of cipro-
floxacin hydrochloride could be improved by a drug
Correspondence to: Naseem A. Charoo (Telephone: 0091-11-
9811397613; Fax: 0091-11-9672244755;
E-mail: naseem102@yahoo.com)
Journal of Pharmaceutical Sciences, Vol. 92, 407–413 (2003)
ß 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association
drug, which would thus increase the application
interval. Aqueous solutions of HPMC and carbopol
are known to gel on heating and increase in pH.
These gels are completely reversible in that they
are formed on heating and increase in pH, yet
liquefy on cooling and at low pH.5–7 Three methods
have been employed to cause phase transition on
the eye surface: change in pH, change in tempera-
ture, and ion activation. Gelation of an HPMC
solution is primarily caused by the hydrophobic
interaction between molecules containing a meth-
oxy substitution. In a solute state at lower tem-
perature, molecules are hydrated and there is little
polymer–polymer interaction other than simple
entanglement. As the temperature is increased,
the molecules gradually lose their water of hyd-
ration, which is reflected in a drop in relative
viscosity. Eventually, when a sufficient but not
complete dehydration of the polymer occurs, a

JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 92, NO. 2, FEBRUARY 2003 407

408 CHAROO, KOHLI, AND ALI
Table 1. Composition of the Viscous Systems
Ingredient
Ciprofloxacin hydrochloride (g)
HPMC K15M (g)
Carbopol 934 (g)
Benzalkonium chloride (% v/v)
Sodium chloride (% w/v)
Acetate buffer of pH 4.4 (mL)
polymer–polymer association takes place, and the
system approaches an infinite network structure
reflected in a sharp increase in relative viscosity.
Carbomers are synthetic high-molecular-weight
polymers of acrylic acid cross-linked with either
allyl sucrose or allyl esters of pentaaerythritol.
They exhibit reverse thermal gelation; that is,
their macroscopic viscosity increases with an in-
crease in temperature. They also exhibit reverse
pH dependent gelation; that is, their viscosity
increases on increasing pH and they gel comple-
tely at pH 7.4. Simultaneous change in both pH
(4.0–7.4) and temperature (25–378C) of the HPMC
and carbopol solutions results in solutions with
higher viscosity. In the present study, sol-to-gel
systems of ciprofloxacin hydrochloride were eval-
uated for rheological characteristics, in vitro re-
lease characteristics, efficacy against induced
bacterial conjunctivitis in rabbits’ eyes, concentra-
tion in aqueous humor, and stability as per the
ICH (International Conference on Harmonization)
guidelines.
EXPERIMENTAL SECTION
Materials
Ciprofloxacin hydrochloride, HPMC K15 M
(HPMC), and carbopol 934 were gifts from
Ranbaxy Research Laboratories (New Delhi,
India). All other chemicals and solvents were of
analytical grade.
Preparation of Sol-To-Gel System
Sol-to-gel systems were prepared by two methods
depending on the sterilization method employed.
Gamma radiation sterilization is the usual method
recommended for sterilization of polymeric de-
vices. To evaluate the effect of gamma radiation
on the physical properties, viscous systems were
JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 92, NO. 2, FEBRUARY 2003
Viscous System
A B C D
0.1875 0.1875 0.1875 0.1875
0.84 0.80 0.60 0.48
0.12 0.10 0.12 0.08
0.02 0.02 0.02 0.02
0.422 0.422 0.422 0.422
50 50 50 50
compared with the formulations sterilized by
filtration. The composition of the formulations is
given in Table 1.
Method A
The calculated amount of ciprofloxacin hydro-
chloride was placed in a volumetric flask and
dissolved in acetate buffer of pH 4.4 under aseptic
conditions. The required amount of sodium chlor-
ide and benzalkonium chloride were added and
mixed thoroughly. The resulting solution was
sterilized by filtration through 0.22-mm Millipore
membrane filter paper. Solutions containing both
HPMC and carbopol 934 were prepared by adding
appropriately weighed amounts of the HPMC and
carbopol. The solution was thoroughly mixed and
equilibrated in a biological shaker for 24 h at
258C. The mixing was continued until a uniform
and clear solution was formed. The resulting
solutions were sterilized by autoclaving. The
solutions were again shaken for 3 h.
The solutions just described were mixed under
aseptic conditions in a sterilized flask and were
thoroughly shaken until a uniform and clear solu-
tion was formed. The solution was transferred into
previously sterilized amber-colored bottles, each
with a cap that was fitted and that carried a
dropper fitted with a teat.
Method B
An appropriate amount of ciprofloxacin hydro-
chloride was placed in a volumetric flask and
dissolved in acetate buffer of pH 4.4. The required
amount of sodium chloride was added to adjust
the isotonicity. Solutions containing both HPMC
and carbopol were prepared by adding appropri-
ately weighed amounts of the HPMC and carbopol
solutions. The resulting solutions were thoro-
ughly mixed and equilibrated for 24 h in a
biological shaker at 258C. The polymer solution
was added to the drug solution and mixed
 CIPROFLOXACIN HYDROCHLORIDE OPHTHALMIC GELS
thoroughly. Preservative was then added, and
mixing was continued until a uniform and clear
solution was formed. Final concentrations were
made by adding required volumes of acetate
buffer of pH 4.4. The solution in the final
container was sterilized by gamma radiation.
The package was exposed to a total dose of 2.5
megarads, and the total dose was given in 24 h.
Rheological Studies
The rheological studies of the samples were car-
ried out with a Brookfield viscometer (RV model).
The pH of the solution was raised from 4.4 to 7.4
by neutralizing with 0.1 N NaOH, and, simulta-
neously, the temperature of the solutions was in-
creased from 21 to 378C by keeping the solutions
in a water bath maintained at 378C. The viscosity
of the samples was recorded before and after
gelifying.
In Vitro Release Studies
In vitro release studies were carried out on sol-to-
gel systems in diffusion cells.8 The diffusion cham-
ber, a circular flat reservoir 4 cm in diameter, was
fitted in a Teflon block. One drop (0.04 mL con-
taining 0.15 mg of the drug) of the viscous system,
equal to one dose, was placed into the cell and was
covered with muslin cloth. This cell was then
fitted into a Teflon block and placed at the bottom
of a 250-mL capacity beaker containing 50 mL of
simulated tear fluid of pH 7.4 at 37
0.58C, which
was kept in a dissolution apparatus (USP XVIII).
The paddle was lowered and rotated at 50 rpm.
Aliquots of medium (3 mL) were withdrawn at
selected time intervals and replaced by 3 mL of
fresh simulated tear fluid. The samples were fil-
tered through Whatmann no. 42 filter paper and
estimated by ultraviolet spectroscopy at 274 nm.
The simulated tear fluid contained 1.34 g of
sodium chloride, 0.40 g of sodium bicarbonate,
0.016 g of calcium chloride, and water to a volume
of 200 mL.
Packaging, Sterilization, and Interaction Studies
The sol-to-gel systems were packed in amber-
colored bottles fitted with closure systems and
were evaluated as per BP (British Pharmaco-
poeia) for sterility, resistance to autoclaving, and
closure efficiency. Interaction studies were car-
ried out, as described next, to investigate any
interaction between drug and polymer as well as
JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 92, NO. 2, FEBRUARY 2003
409
to study the effect of gamma radiation on cipro-
floxacin hydrochloride.
Ultraviolet (UV) Scanning
The sterilized and nonsterilized viscous systems
were dissolved in simulated tear fluid of pH 7.4.
After filtration through Whatmann filter paper
no. 42, the solutions were scanned for UV absorp-
tion between 200 and 400 nm. UV scans of the
placebo formulations were also run and were
compared with those of medicated formulations.
Assay
An accurate amount of ciprofloxacin hydrochlor-
ide was dissolved in simulated tear fluid of pH 7.4,
and the absorbance of the resulting solutions was
determined at 274 nm. Drug content was calcu-
lated to estimate the percentage recovery of the
loaded drug.
Infrared (IR) Spectroscopy Studies
The IR spectra studies were performed on steri-
lized and nonsterilized viscous systems, and the
spectra were compared with the IR spectra of pure
drug and placebo formulations.
Thin-Layer Chromatography (TLC) Studies
The following TLC system was used: thin layer,
Silicon gel 60 F-254; eluent, acetonitrile:ammo-
nia:methanol: ichloromethane (1:2:4:4); sample,
ciprofloxacin hydrochloride dissolved in acetic
acid (10 mg/mL); visualization, in UV light at
254 nm. The sterilized and nonsterilized viscous
systems were dissolved in acetic acid to achieve a
concentration of 10 mg/mL The solutions were
filtered through Whatmann filter paper no. 42,
and the filtered solutions were applied onto silica
gel plates.
Microbiological Studies
The microbiological studies were carried out
to ascertain the biological activity of ophthalmic
sol-to-gel system against microorganisms. Sta-
phylococcus aureus was used as the test micro-
organism. A layer of agar (20 mL) seeded with the
test microorganism was allowed to solidify in the
Petri plate. The viscous system containing 0.15 mg
of the drug was poured into the bore made with a
sterile borer. After 4 h, the plates were incubated
at 378C for 18 h. Results were compared with the
placebo formulations.
410 CHAROO, KOHLI, AND ALI
In Vivo Studies
From the standpoint of animal welfare and as per
guiding principles for the care and use of labo-
ratory animals in India, the minimum number of
animals were used to achieve the purpose of the
research work. Rabbits of either sex, weighing
1.5–2 kg were procured from the animal house of
Jamia Hamdard, New Delhi, India. The animals
were randomly distributed into various groups
and transferred to an animal holding room. They
were housed one per cage in plastic cages with
filter tops. Animals had access to food and water
at all times.
All the animals were sacrificed at the end of
study by carbon dioxide euthanasia.
Estimation of Ciprofloxacin Hydrochloride
in Aqueous Humor of Rabbits’ Eyes
The in vivo release studies were performed in
albino rabbits because rabbits’ eyes simulate an
adult human eye with respect to size, shape, phy-
siology, and composition of tears.9 First, 0.15 mg
of the viscous system (equal to one dose) was
applied to the right eye of the rabbit, once a day.
Ciprofloxacin hydrochloride drops (0.3 % w/v;
marketed preparation) were placed into the left
eyes of the rabbits, three times a day (3 drops per
dose). Then, 200 mL of the aqueous humor was
withdrawn with a 26-gauge needle at appropriate
time intervals (i.e., 4, 8, and 24 h). The amounts of
ciprofloxacin hydrochloride permeated into the
aqueous humor were quantitated by a modifica-
tion of the method of Isavadharm et al.10 After
being vortexed for 30 s and centrifuged for 15 min
at 2000 rpm, 20 mL of the sample was directly
injected into the high-performance liquid chro-
matography (HPLC) apparatus. The HPLC anal-
X1  i2  ½ðX1  iÞ2 =n1 þ X2  i2  ½ðX2  iÞ2 =n2
s2 ¼
n1 þ n2  2
ysis chromatographic conditions were as follows:
HPLC mode, Shimadzu; flow rate, 1 mL/min;
mobile phase, tetrabutyl ammonium hydroxide
solution in water (pH 2.5–2.7): acetonitrile (91:9);
column, Nucleosil; detector, fluorescence; extinc-
tion, 277 nm; and emission, 456 nm.
Animal Studies
Bacterial conjunctivitis was induced in rabbits’
eyes by exposing them to bacterial strains of
JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 92, NO. 2, FEBRUARY 2003
Staphylococcus aureus and Escherichia coli.
Treatment was initiated 24 h later. Five rabbits
were selected for the study. The right eye of each
animal was treated with sol-to-gel system. One
drop of drug containing 0.15 mg of drug per dose
was instilled every 24 h for 5 days. The left eye of
each animal was treated with 2–3 marketed eye
drops, three times a day for the duration of study.
Eyes of each animal were observed every day for
the duration of the study for the following
parameters: redness of the mucous membrane
of the eye: observed visually and graded from 0 to
4 (i.e., 0 ¼ absent; 1 ¼ mild; 2 ¼ moderate;
3 ¼ severe; 4 ¼ very severe); lacrimal secretion:
graded from 0 to 3 (i.e., 0 ¼ normal; 1 ¼ slightly
more than normal; 2 ¼ more than normal;
3 ¼ abnormally more than normal); mucoidal
discharge: whitish to yellowish-white semisolid
discharge if any was noted and graded from 0 to 3
(i.e., 0 ¼ absent; 1 ¼ little; 2 ¼ more; and 3 ¼ much
more); response to ocular stimulus: assessed by
shining torch light on the eye from a particular
distance, observing the response to this stimulus,
and grading the response from 0 to 2 (i.e.,
0 ¼ normal; 1 ¼ faster; 2 ¼ very fast); swelling of
eyelid: graded from 0 to 2 (i.e., 0 ¼ absent;
1 ¼ slight; 2 ¼ more).
Treatment effects were compared with those of
marketed formulations, and significance was
determined by the following t test:
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
t ¼ X1  X2 =s ¼ n1 n2 =n1 þ n2 ð1Þ
where X1 is the mean of the first set of samples
of n1 observations (marketed eye drops), X2 is the
mean of the second set of samples of n2 observa-
tions (viscous system), and s is the pooled
variation of two squares. Equation 2 was used to
calculate s2:
ð2Þ
where Sx21  i is the sum of squares of observations
of the first sample, Sx1  i is the sum of observa-
tions of the first sample, Sx22  i is the sum of
squares of observations of the second sample, and
Sx2  i is the sum of observations in the second
sample.
Significance levels (p < 0.05) were determined
by a two-tailed t test. The theoretical t value was
2.306 at this level of degrees of freedom. Treatment
was given significance (s) if the t value exceeded
the theoretical t value. If the treatment t value did
 CIPROFLOXACIN HYDROCHLORIDE OPHTHALMIC GELS
not exceed the theoretical t value, then the
treatment was considered as nonsignificant (NS)
compared with marketed eye drops.
Stability Studies
Stability studies were carried out on ophthalmic
sol-to-gel systems according to ICH guidelines. A
sufficient quantity of sol-to-gel system in amber-
colored bottles was stored in a desiccator contain-
ing a saturated solution of sodium chloride, which
gave a relative humidity of 75%. The desiccator
was placed in a hot air oven maintained at a
temperature of 40
0.58C, and samples were
withdrawn at 0, 30, 60, and 90 days. The loga-
rithms of percent drug remaining were calculated
and plotted against time in days. The degradation
rate constant was deduced with equation slope ¼
K/2.303, where K is a degradation rate constant.
RESULTS AND DISCUSSION
The objective of the present research work was to
develop controlled drug delivery systems of cipro-
floxacin hydrochloride with improved patient com-
pliance and better therapeutic efficacy. Because of
its short half-life of elimination and polar char-
acteristics, the bioavailability of ciprofloxacin
hydrochloride is very low and it is thus necessary
to apply the eye drops three times daily. To
overcome this shortcoming, a controlled drug deli-
very system of ciprofloxacin hydrochloride was
developed for the continuous release of the drug
for 24 h. Aqueous solutions of HPMC are known to
gel on heating. These gels are completely rever-
sible in that they are formed on heating, yet they
will liquefy on cooling. Carbopol 934 exhibits
reverse thermal gelation; that is, its macroscopic
viscosity increases with an increase in tem-
perature. HPMC and carbopol 934 also exhibit
reverse pH-dependent gelation; that is, their
viscosities increase on increasing pH and they
gel completely at pH 7.4 (pH of the eye). Thus, by
using HPMC and carbopol 934, sol-to-gel phase
transition could be achieved by both changes
in temperature and pH when the formulation was
instilled into the cul de sac of the eye. Maximum
phase transition was achieved when HPMC and
carbopol 934 were used in a ratio of 5:1. The
environment of the conjunctival sac favors the
phase transition of HPMC and carbopol 934
solution to the gel form. Drainage from the pre-
corneal area would therefore be considerably
reduced.
JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 92, NO. 2, FEBRUARY 2003
411
Figure 1. In vitro release rate curves of ciprofloxacin
hydrochloride from ophthalmic sol-to-gel system C.
Almost 93% of the drug was released from the
optimized formulation over a period of 24 h in
in vitro release studies. As shown in Figure 1, the
drug was released according to zero-order kinetics.
The extended and zero-order release from the gel
might be due to the hydroxypropyl and meth-
oxy substituents of HPMC that render HPMC
hydrophobic. All the samples passed the tests for
sterility, leakage, water vapor transmission, remo-
vability, and resistance to autoclaving. No change
in physical appearance of the viscous system due to
gamma radiation was observed. The UV absorp-
tion spectra for pure drug formulations before and
after sterilization were quantitatively similar,
with similar lmax at 274 nm. When assayed, almost
97% of the loaded drug was recovered from the
viscous system. The IR spectra of the viscous
system before and after sterilization showed
similar peaks at 1700, 1625, 1275, 1230, and
800 cm1, which confirmed that no ingredient
was affected by gamma radiation in the dosage
form and no irradiated product was formed within
the dosage form. The main peaks of the dosage
form were similar to the those of the pure drug in
the IR spectra. The IR spectra of placebo formula-
tions before and after sterilization exhibited
similar patterns, which indicated that there was
no effect of gamma radiation on the ingredients of
Table 2. In Vitro Inhibition of Growth of
Microorganisms (Staphylococcus aureus) Over One Day
by Ophthalmic Gel C Containing Ciprofloxacin
Hydrochloride (0.15 mg)
Hours of Incubation Zone Diameter (mm)
18 15
24 23
412 CHAROO, KOHLI, AND ALI

advantage of viscous formulations. Thus, viscous

Figure 2. Concentration of drug in aqueous humor
versus time for ophthalmic sol-to-gel system C and
marketed eye drops.
the formulations. The Rf value of 0.54 obtained in
TLC studies was the same as that of the pure drug.
It could thus be concluded that there was no
interaction between the drug and polymer and no
interaction due to gamma radiation.
The drug was active against the selected micro-
organisms as indicated by clear zones of inhibition
(see Table 2).
The amount of ciprofloxacin hydrochloride in
aqueous humor was determined after the applica-
tion of the viscous system in the rabbit’s eye at
different time intervals (i.e., 4, 8, and 24 h). The
reported minimum inhibitory concentration (MIC-
90) of ciprofloxacin hydrochloride is 0.380

0.328 mg/mL against the selected microorganism.
As shown in Figure 2, the MIC-90 of drug in
aqueous humor was achieved quickly in the case of
viscous formulations and the drug concentration
was maintained above MIC-90 for >20 h. In con-
trast, in the case of marketed eye drops, a sharp
increase in aqueous humor drug concentration
was observed at 4 and 8 h. At 24 h, drug was not
detected in aqueous humor from marketed for-
mulations. The latter result represents the main
formulations overcame the seesaw pattern of
aqueous humor drug concentration level versus
time profile of the conventional marketed eye
drops.
Bacterial conjunctivitis was induced by instil-
ling mixed strains of Staphylococcus aureus and
Escherichia coli in rabbits’ eyes. Treatments were
given with marketed eye drops and the sol-to-gel
system. The eyes were observed for redness, lacri-
mal secretion, mucoidal discharge, swelling of
eyelid, and response to ocular stimuli on score
basis up to 5 days. The results are shown in Table 3.
An improvement in the symptoms was observed
for the sol-to-gel system. The infection was suc-
cessfully treated with sol-to-gel system in a much
shorter time compared with the marketed eye
drops. The results were analyzed statistically by
applying a two-tailed t test (p < 0.05) and the
results are shown in Table for two tales, as shown
in Table 4.
Improvement in redness occurred after 1 day in
the case of the sol-to-gel system as compared with
on the second day of treatment in the case of
marketed eye drops. Similarly, significant changes
in measured parameters were observed earlier
following treatment with the sol-to-gel system as
compared with treatment with eye drops. Thus,
symptoms mainly associated with conjunctivitis
were controlled better with viscous systems than
marketed eye drops. Finally, accelerated stability
studies at elevated temperature and humidity
revealed that the sol-to-gel system has high
stability; that is, the shelf-life is 2 years as per
the ICH guidelines. The degradation rate constant
for the formulation was 4.5292  104 day1, as
shown in Figure 3. Because the overall degrada-
tion is <5%, a tentative shelf-life of 2 years may be
assigned to the formulations.

Table 3. Mean Scores and Standard Deviation (
SD) for Severity of Redness, Lacrimal Secretion, Mucoid
Discharge, Response to Ocular Stimulus, and Swelling of Eyelida

Response to Ocular
Redness Lacrimal Secretion Mucoid Discharge Stimulus Swelling of Eyelid
No. of
Days ED VS ED VS ED VS ED VS ED VS
1 3.8
0.44 3.2
0.44 2.4
0.54 2.2
0.44 2.6
0.54 2.2
0.44 2.0
0.00 2.0
0.00 2.0
0.00 1.6
0.54
2 3.2
0.44 2.8
0.54 2.2
0.44 1.6
0.54 2.0
0.00 1.0
0.00 1.6
0.54 2.0
0.0 1.6
0.54 1.2
0.44
3 2.6
0.54 2.2
0.44 1.6
0.54 1.0
0.00 1.6
0.54 0.4
0.54 1.0
0.00 1.0
0.00 1.4
0.54 0.6
0.54
4 2.4
0.54 1.4
0.54 1.0
0.00 0.8
0.44 1.0
0.00 0.2
0.44 0.4
0.54 0.4
0.54 1.0
0.00 0.2
0.44
5 2.2
0.44 0.6
0.54 0.4
0.54 0.4
0.54 0.2
0.44 0.0
0.00 0.0
0.00 0.0
0.00 0.8
0.44 0.0
0.00
a
N, 5; ED, eye drops; VS, viscous system.

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 CIPROFLOXACIN HYDROCHLORIDE OPHTHALMIC GELS 413

Table 4. Significance t Test Results of Ophthalmic Sol-to-Gel C Versus Eye Drops for
Improving the Symptoms of Conjunctivitis in Rabbits Eye (viz., Redness, Lacrimal
Secretion, Mucoid Discharge, Response to Ocular Stimulus, and Swelling of Eyelid)a

Lacrimal Mucoid Response to Swelling

No. of Days Redness Secretion Discharge Ocular Stimulus of Eyelid
1 2.1198 06320 1.264 0 1.6322
NS NS NS NS NS
2 1.4132 1.8960 1.6322 1.2640
NS NS NS NS
3 1.2640 2.4483 3.4617 0 2.3078
NS S S NS NS
4 2.8847 0.9993 3.9974 0 3.9974
S NS S NS S
5 5.0560 0 0.9993 0 3.9974
S NS NS NS S
a
Theoretical t value of p  0.05 for two tails, 2.306. S, significant (if calculated t values are greater
than theoretical t values); NS, nonsignificant.

2. Kamath R, Singh UV, Udupa N. 1993. Evaluation

Figure 3. Plot of log % of drug remaining versus time
for ophthalmic sol-to-gel system C.
CONCLUSIONS
On the basis of in vitro, in vivo, and microbio-
logical studies it could be concluded that cipro-
floxacin hydrochloride, a potent antibacterial
agent, could be successfully administered via a
sol-to-gel system for the treatment of bacterial
conjunctivitis.
10. Isavadharm PT, Keeratithakul D, Watt G, Webster
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