Acta Pharm.

62 (2012) 93–104 Original research paper

DOI: 10.2478/v10007-012-0002-5

Design and evaluation of moxifloxacin

hydrochloride ocular inserts

PRAVIN K. PAWAR1* The objective of the present investigation was to prepare

RAJESH KATARA2
and evaluate ocular inserts of moxifloxacin. An ocular
DIPAK K. MAJUMDAR2
insert was made from an aqueous dispersion of moxiflo-
1 Chitkara College of Pharmacy, Chitkara xacin, sodium alginate, polyvinyl alcohol, and dibutyl
University, Chandigarh-Patiala National phthalate by the film casting method. The ocular insert
Highway, Rajpura, Rajpura-140401 (5.5 mm diameter) was cross-linked by CaCl2 and was
Patiala, Punjab, India coated with Eudragit S-100, RL-100, RS-100, E-100 or
L-100. The in vitro drug drainage/permeation studies were
2 Department of Pharmaceutics, Delhi carried out using an all-glass modified Franz diffusion
Institute of Pharmaceutical Sciences and cell. The drug concentration and mucoadhesion time of
Research (formerly College of Pharmacy) the ocular insert were found satisfactory. Cross-linking
University of Delhi, Pushp Vihar and coating with polymers extended the drainage from
Sector III, New Delhi-110017, India inserts. The cross-linked ocular insert coated with Eud-
ragit RL-100 showed maximum drug permeation com-
pared to other formulations.
Keywords: moxifloxacin, ocular insert, goat cornea
Accepted December 16, 2011

Eyes are among the most readily accessible organs in terms of location in the body.
The physiological constraints of the eye render this organ impervious to foreign sub-
stances, thus presenting a constant challenge to the formulator to circumvent the protec-
tive barriers of the eye without causing permanent tissue damage (1). All ocular thera-
peutics have been mostly administered to the eye as simple aqueous eye drops. About
90 % of the dose applied topically from such solutions is lost due to pre-corneal losses
(lacrimation and drainage), which leads to poor availability and frequent dosing is re-
quired for the instillation to achieve an adequate level and therapeutic effect (2). The
standard treatment of severe bacterial keratitis requires frequent administration of fluo-
roquinolone eye drops (3). However, this regimen is not only disruptive to the patient
and usually necessitates hospitalization, but it has also been associated with toxicity to
the corneal epithelium (4, 5). To overcome these limitations, ocular inserts seem promis-
ing by prolonging the contact time with improved efficiency of the therapy and patient
compliance. Ocular inserts offer many advantages over conventional dosage forms, like

* Correspondence; e-mail: pkpawar80@[Link]

93
P. K. Pawar et al.: Design and evaluation of moxifloxacin hydrochloride ocular inserts, Acta Pharm. 62 (2012) 93–104.

increased ocular residence, possibility of releasing drugs at a slow and constant rate, ac-
curate dosing, and avoidance of toxicity due to preservative and increased shelf life (6).
Ocular inserts of ciprofloxacin hydrochloride (7) and ofloxacin (8) have been designed to
improve ocular availability.
Moxifloxacin, [1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-
6H-pyrrolol (3,4b) pyridin-6-yl]-4-oxo-3-quinoline carboxylic acid], is a fourth generation
fluoroquinolone with a methoxy group at the C-8 position and a bulky C-7 side chain
(9). Moxifloxacin has increased activity against S. aureus compared to second and third
generation fluoroquinolones. Bactericidal activity of moxifloxacin is mediated by the in-
hibition of DNA gyrase (topoisomerase II) and topoisomerase IV, essential enzymes in-
volved in bacterial DNA replication, transcription, repair and recombination (10). Effects
of the formulation factor on in vitro corneal permeation of moxifloxacin from aqueous
drops have been investigated and the results showed that moxifloxacin 0.5 % (m/V) oph-
thalmic solution (pH 7.2) containing benzalkonium chloride (0.01 %) (BAK) and EDTA
(0.01 %) provides maximum in vitro ocular availability through all excised mammalian
corneas (11). The in vitro permeation profile of moxifloxacin oil drops has been reported
(12). Oil drops containing castor oil with benzyl alcohol provided maximum in vitro per-
meation through all the corneas. Aqueous and oily drops of moxifloxacin showed better
permeation characteristics but these formulations require frequent instillation to achieve
therapeutic concentration due to shorter precorneal residence time. Taking the above in-
formation in account, the purpose of the current study was to formulate ocular inserts of
moxifloxacin that would be capable of prolonging the contact time, thereby potentially
enhancing intra-corneal delivery of ophthalmic medicament.

EXPERIMENTAL

Materials
Moxifloxacin hydrochloride (99.97 % purity on anhydrous basis) was obtained from
Ranbaxy Laboratories (India) as a gift. Sodium alginate, Eudragit S-100 (anionic metha-
crylic acid-methyl methacrylate copolymer), Eudragit RL-100 (acrylic acid and metha-
crylic acid ester copolymer containing 10 % trimethylammonium methacrylate chloride),
Eudragit RS-100 (acrylic acid methacrylic acid ester copolymer containing 5 % trimethyl-
ammonium methacrylate chloride), Eudragit E-100 (cationic polymer based on dime-
thylaminoethyl methacrylate and other neutral methacrylic acid esters), Eudragit L-100
(anionic copolymer based on methacrylic acid and methyl methacrylate) were obtained
from Jubilant Organosys (India) as gift samples. Polyvinyl alcohol (PA) and dibutyl
phthalate were obtained from the Central Drug House (India) and S.D. Fine chemicals
Ltd (India), respectively. All other chemicals were of analytical grade. Fresh goat eyeball
was obtained from a butcher’s shop. The method of cornea dissection and the apparatus
used in permeation studies were the same as described previously (13).

94
P. K. Pawar et al.: Design and evaluation of moxifloxacin hydrochloride ocular inserts, Acta Pharm. 62 (2012) 93–104.

Preparation of ocular inserts

The moxifloxacin control ocular insert (MIF1) was made from an aqueous disper-
sion (40 mL) of moxifloxacin hydrochloride (400 mg), sodium alginate (0.25 g), polyvi-
nyl alcohol (PVA) (1.5 g), and dibutyl phthalate (0.3 mL) by the film casting method. Oc-
ular insert (5.5 mm diameter) was cross-linked (MIF2) by CaCl2 (0.2 %, m/V) by dipping
and drying 5 times. Similarly, the cross-linked insert was coated with different grades of
Eudragit polymer 0.2 % (m/V) in isopropyl alcohol and acetone by the dip and dry me-
thod (Table I). The polymers used were Eudragit S-100 (MIF3), Eudragit RL-100 (MIF4),
Eudragit RS-100 (MIF5), Eudragit E-100 (MIF6) and Eudragit L-100 (MIF7). The mass gain
of the ocular insert after coating with polymer was found to be in the range 23.4–29.6 %.

Table I. Compositions of moxifloxacin insert formulations for ocular delivery

Polymer composition Plasticizer (dibutyl Cross-linking agent Coating material

Formulation CaCl2 (%, m/V)
(18+12+70 %, m/m) phthalate, %, V/V) (0.2 %, m/V)
MIF1 MOX + SA + PVA 0.12 – –
MIF2 MOX + SA + PVA 0.12 0.2 –
MIF3 MOX + SA + PVA 0.12 0.2 Eudragit S-100
MIF4 MOX + SA + PVA 0.12 0.2 Eudragit RL-100
MIF5 MOX + SA + PVA 0.12 0.2 Eudragit RS-100
MIF6 MOX + SA + PVA 0.12 0.2 Eudragit E-100
MIF7 MOX + SA + PVA 0.12 0.2 Eudragit L-100
MOX – moxifloxacin, SA – sodium alginate, PVP– polyvinyl alcohol

Physicochemical evaluation of ocular inserts

Thickness uniformity. – Insert thickness (5.5 mm diameter) was measured at five dif-
ferent points using a Micrometer screw gauge (Mitutoyo Co., Japan) and the mean insert
thickness was noted (n = 3).

Drug content uniformity. – Three inserts were taken out of the film and drug concen-
tration determined. The uncoated ocular insert was dissolved in 10 mL of 0.1 mol L–1
HCl while the coated insert was dissolved in 10 mL of acetone. The volume was made
up to 100 mL with distilled water and the solution was filtered. The drug in the filtrate
was analyzed by measuring absorbance at 291 nm in a spectrophotometer 1601 (Shimad-
zu, Japan). The experiment was done in triplicate.

Mucoadhesion time
The mucoadhesion time was determined (in triplicate) after application of coated or
uncoated ocular inserts (5.5 mm diameter, 0.40–0.45 mm thickness) on a freshly cut goat
eyelid. The eyelid was fixed on the bottom of a beaker with cyanoacrylate glue. Ocular
insert (coated or uncoated) was attached to the mucosal surface of the eyelid by apply-

95
P. K. Pawar et al.: Design and evaluation of moxifloxacin hydrochloride ocular inserts, Acta Pharm. 62 (2012) 93–104.

ing a light force with a fingertip for 20 s. The beaker was filled with 800 mL of bicarbon-
ate Ringer solution pH 7.4 and stirred at a rate of 150 rpm at room temperature (14). The
time needed for complete detachment of the insert from the mucosal surface was consid-
ered as mucoadhesion time.

Drug permeation
The in vitro drug permeation studies were carried out by putting the ocular insert
(5.5 mm in diameter) on Millipore membrane filter (0.15 mm); between the donor and re-
ceptor compartments of an all-glass modified Franz diffusion cell. The Millipore mem-
brane filter was used to simulate the corneal epithelial barrier as isolated cornea will not
remain viable beyond 4 h. To simulate the tear flow, the donor compartment was infused
with bicarbonate Ringer, pH 7.4, at a flow rate of 20 mL min–1 throughout the study. The
drained sample was monitored for moxifloxacin at 291 nm every hour. Similarly, a
1.0-mL sample was withdrawn at hourly intervals from the receptor compartment (con-
taining 10 mL bicarbonate Ringer, pH 7.4, under stirring at 37 °C) and the drug permea-
ted was measured. Each withdrawn sample was replaced with an equal volume of fresh
bicarbonate Ringer. Drug permeation experiments were also carried out using freshly
excised goat cornea for 4 h. At the end of the experiment, each cornea (freed from adher-
ing sclera) was weighed, soaked in 1 mL of methanol, dried overnight at 90 °C and re-
weighed. Corneal hydration was calculated from the difference in masses.
The drug permeation data was plotted according to zero-order, first-order kinetics,
Higuchi equation and Korsmeyer-Peppas equation (15).

Fourier transform infrared (FTIR) spectroscopy

The FTIR spectra of the pure drug and physical mixture (moxifloxacin, polyvinyl al-
cohol and sodium alginate) were taken as KBr pellets in the range of 4000–650 cm–1 (Per-
kin Elmer Model 1600 FT-IR spectrophotometer, USA). The infrared analysis of all in-
serts was carried out in the same range by ATR-IR spectroscopy (Perkin Elmer Model
1600 FT-IR spectrophotometer with ATR mode (Pike Miracle ATR Accessory, Perkin El-
mer, USA).

In vivo study
Selected ocular inserts (MIF4 and MIF5) sterilized using g-irradiation were used for
in vivo drug release studies. The protocol on the use of animals (albino rabbits) was ap-
proved by the Institutional Ethics Committee. Two groups of ten healthy albino rabbits
were used to study the drug release in vivo from formulations that showed satisfactory
in vitro drug release (16). Each rabbit was kept under good hygienic conditions in order
to avoid vulnerability to any disease, including ophthalmic types. Selected ocular inserts
were placed in the cul-de-sac of each rabbit while the other eye served as a control. At pe-
riodic intervals (1–10 h) the inserts were taken out carefully from the cul-de-sac of each
rabbit and analyzed for the remaining drug content. The remaining drug was subtracted
from the initial drug content of the insert, which gave the amount of drug released in the
rabbit eye.

96
P. K. Pawar et al.: Design and evaluation of moxifloxacin hydrochloride ocular inserts, Acta Pharm. 62 (2012) 93–104.

Stability of ocular inserts

Stability studies were carried out on ocular insert formulations according to ICH
guidelines (17). A sufficient number of ocular inserts (packaged in aluminum foils) were
stored in a humidity chamber with a relative humidity of 75 ± 5 % and temperatures of
40 ± 2 °C or at room temperature. Samples were withdrawn at time 0, 3 weeks, 6 weeks,
3 months and 6 months. Ocular inserts were also evaluated for their physical character-
istics (color) and analyzed for drug concentration. The degradation rate constant was
determined from the plot of logarithm of the remaining drug vs. time.

RESULTS AND DISCUSSION

Physicochemical evaluation and mucoadhesion time of ocular inserts

The thickness of ocular inserts was found to be from 0.40 ± 0.00 to 0.45 ± 0.06 milli-
meters. Drug concentration of the ocular insert without cross-linking and uncoated (con-
trol MIF1) was maximum (i.e., 0.149 mg mm–2), followed by the cross-linked ocular in-
sert (i.e., 0.122 mg mm–2) and coated ocular insert (i.e., 0.115 mg mm–2) (Table II). Inserts
were supposed to be retained in the lower conjunctival cul-de-sac and accordingly the
mucoadhesive property of the inserts was evaluated. The mucoadhesion time of various
ocular inserts was found to be 0.32–1.07 h. Control ocular inserts showed maximum mu-
coadhesion, which appears to be due to the presence of hydroxyl groups in the inserts
(contributed by PVA and alginate), which could form hydrogen bonding with the mu-
cosa. Cross-linking by CaCl2 reduced the mucoadhesion. On coating with Eudragit poly-
mers, cross-linked insert further reduced mucoadhesion as the surface hydroxyl group
of the insert got coated with polymer having a carboxylic group and/or quaternary am-
monium group. Thus, taking both mucoadhesion and sustained drug release into con-
sideration, the cross-linked ocular insert coated with Eudragit RL-100 appears to be pro-
mising (Table II).

Fourier transform infrared (FTIR) spectroscopy

FTIR spectra of moxifloxacin hydrochloride (Fig. 1) showed aromatic C=C stretch-
ing at 1621, 1515 and 1454 cm–1 and C–H bending for substituted benzene at 873 cm–1.
Besides, spectra also showed carboxylic acid C=O stretching at 1705 cm–1, C–N stretch-
ing at 1350 cm–1, stretching of monofluorobenzene at 1183 cm–1. Spectra of a physical
mixture of the drug, PVA and sodium alginate showed peaks at 3520 cm–1due to stretch-
ing of the hydroxyl group, 2920 cm–1 due to C–H stretching and 1023 cm–1 due to
C–O–C stretching (which appears to be contributed by PVA and alginate), along with
drug peaks. The ATR spectra of the blank insert of PVA-alginate showed shifting of the
hydroxyl peak from 3520 to 3306 cm–1 due to intermolecular hydrogen bonding, C–H
stretching at 2913 and C–O–C stretching at 1027 cm–1. Uncross-linked and cross-linked
inserts showed hydroxyl stretching, C–H stretching along with asymmetric C–O–C stret-
ching at 1247 cm–1 and symmetric C–O–C stretching at 1090 and 1023 cm–1, indicating
branching on the carbon atom adjacent to the oxygen atom. Besides, ATR spectra showed

97
98
Table II. Amount of moxifloxacin permeated and drained from ocular insert through Millipore membrane filter and goat cornea

Millipore filter membrane Goat cornea

Muco- Drug
Thickness
Formulation adhesive concentration Drug Drug Drug Drug Corneal
(mm)a
time (h)a (mg mm–2)a permeated drained permeated drained hydration
(%) (%) (%) (%) (%)

34.95 ± 2.45 40.61 ± 0.47 15.57 ± 0.54 24.30 ± 0.34

MIF1 0.404 ± 0.003 1.07 ± 0.03 0.149 ± 0.03 76.02 ± 0.12
(5 h) (5 h) (4 h) (4 h)
49.63 ± 1.21 39.81 ± 0.85 17.42 ± 0.20 21.47 ± 0.39
MIF2 0.403 ± 0.003 0.90 ± 0.03 0.122 ± 0.001 76.61 ± 0.47
(6 h) (6 h) (4 h) (4 hrs)
56.77 ± 2.21 28.83 ± 0.81 17.47 ± 0.19 17.70 ± 0.04
MIF3 0.440 ± 0.003 0.35 ± 0.03 0.115 ± 0.002 76.72 ± 0.58
(7 h) (7 h) (4 h) (4 h)
68.42 ± 1.83 30.38 ± 0.24 18.21 ± 0.11 20.66 ± 0.13
MIF4 0.444 ± 0.055 0.32 ± 0.02 0.115 ± 0.001 76.99 ± 0.85
(9 h) (9 h) (4 h) (4 h)
59.98 ± 0.19 34.05 ± 0.70 17.51 ± 0.08 21.16 ± 0.51
MIF5 0.442 ± 0.003 0.33 ± 0.02 0.115 ± 0.001 76.58 ± 0.44
(7 h) (7 h) (4 h) (4 h)
52.43 ± 2.19 35.61 ± 1.57 17.20 ± 0.27 23.76 ± 0.33
MIF6 0.441 ± 0.003 0.42 ± 0.02 0.115 ± 0.001 76.02 ± 0.12
(6 h) (6 h) (4 hrs) (4 h)
53.29 ± 2.17 37.14 ± 0.55 17.22 ± 0.01 21.91 ± 0.18
MIF7 0.453 ± 0.003 0.35 ± 0.03 0.115 ± 0.001 76.39 ± 0.25
(5 h) (5 h) (4 h) (4 h)
a Mean ± SD, n = 3.
P. K. Pawar et al.: Design and evaluation of moxifloxacin hydrochloride ocular inserts, Acta Pharm. 62 (2012) 93–104.
P. K. Pawar et al.: Design and evaluation of moxifloxacin hydrochloride ocular inserts, Acta Pharm. 62 (2012) 93–104.

d
Transmittance (%)

4000 3000 2000 1500 1000 650

Wavenumber (cm–1)

Fig. 1. FTIR spectra of: a) blank insert (without moxifloxacin), b) moxifloxacin, c) physical mixture
of the drug, PVA and sodium alginate, d) control insert (not cross-linked and uncoated), MIF1, e)
cross linked insert (CaCl2), MIF2, f) optimal formulation (Eudragit RL-100), MIF4, g) Eudragit
RS-100, MIF5, h) Eudragit S-100, MIF3, i) Eudragit E-100, MIF6, j) Eudragit L-100, MIF7.

aromatic C=C stretching, C=O stretching and C–N stretching. All the coated inserts sho-
wed aromatic C=C stretching at usual positions, indicating incorporation of moxifloxa-
cin and peaks for ester at 1730 cm–1, since acrylate polymers are esters. It would be im-
portant to mention here that ATR spectra provide information on the surface functional
groups. Major characteristic peaks of moxifloxacin were found in the entire coated ocu-
lar insert, confirming the presence of the drug in the polymer without interaction.

In vitro/ex vivo permeation study

The results are shown in Table II, indicating that the in vitro drug release from the
plain ocular insert (control) was sustained for 5 h. The drug release from MIF2 was ex-
tended up to 6 h. Formulation MIF6 did not have any effect on drug release, while MIF3
and MIF5 could sustain drug release up to 7 h. After coating with different grades of
Eudragit, drug release from ocular inserts was found to be sustained due to the presence
of polymeric film. Among all formulations, MIF4 showed the best sustaining effect. The
MIF4 formulation gave 68.4 % drug permeated through the Millipore membrane filter
after 9 hours.

99
P. K. Pawar et al.: Design and evaluation of moxifloxacin hydrochloride ocular inserts, Acta Pharm. 62 (2012) 93–104.

To mimic real life conditions, permeation studies were then conducted with freshly
excised goat cornea and the results are shown in Table II. Considering cornea viability,
the experiment was conducted for 4 h and the drug permeation from inserts ranged be-
tween 15.6 and 17.5 %, which was less than the permeation observed with the Millipore
membrane filter in 4 h. Millipore membrane filter acts as a mechanical barrier to drug
diffusion while cornea [made of epithelium (lipophilic), stroma (hydrophilic), and endo-
thelium (less lipophilic than epithelium)] acts as a lipophilic-hydrophilic barrier and the
drug will have to partition through the barrier for corneal penetration. Accordingly, per-
meation through the cornea would be lower compared to that across the Millipore mem-
brane filter. The corneal hydration level was found to be below 80 % in each experiment,
indicating the inserts would not cause any damage to the cornea.
The release profiles of ocular inserts were treated with the Korsmeyer-Peppas equa-
tion and slope values were > 0.89, indicating super case II type of drug release from ocu-
lar inserts through the Milipore membrane filter and excised goat cornea (15). Thus, all
formulations followed the Korsmeyer-Peppas kinetics model (Table III).

In vivo drug release study

Formulations MIF4 and MIF5 were selected for in vivo drug release studies on the
basis of maximum mucoadhesion and better sustained behavior of the drug among all
insert formulations. Ocular inserts were removed carefully at hourly intervals (from

Table III. Kinetics of in vitro drug release from ocular inserts through Millipore membrane filter
and goat cornea

R2
Mechanism
Formu- Zero-ordera First-ordera Higuchia Korsmeyer-Peppasa
of drug
lation
Millipore Goat Millipore Goat Millipore Goat Millipore Goat releasea
membrane cornea membrane cornea membrane cornea membranea corneaa
Non-
MIF1 0.8482 0.9938 0.9432 0.9979 0.9877 0.9511 0.9988 0.9997
-Fickian
Non-
MIF2 0.9781 0.9919 0.9622 0.9969 0.9871 0.9536 0.9992 0.9999
-Fickian
Non-
MIF3 0.9444 0.9930 0.9634 0.9975 0.9831 0.9514 0.9963 1.000
-Fickian
Non-
MIF4 0.9653 0.9926 0.9625 0.9983 0.9742 0.9515 0.9982 0.9993
-Fickian
Non-
MIF5 0.9626 0.9922 0.9748 0.9978 0.9891 0.9537 0.9991 0.9999
-Fickian
Non-
MIF6 0.9688 0.9889 0.9654 0.9950 0.9712 0.9577 0.9964 0.9999
-Fickian
Non-
MIF7 0.9642 0.9938 0.9678 0.9979 0.9702 0.9511 0.9964 0.9997
-Fickian
a n = 3.

100
P. K. Pawar et al.: Design and evaluation of moxifloxacin hydrochloride ocular inserts, Acta Pharm. 62 (2012) 93–104.

1–10 hours) and analyzed for residual drug content. The drug was subtracted from the
initial content of the insert and gave the amount of drug released in the rabbit eye. Fig. 3
presents the cumulative drug release (%) from formulations MIF4 and MIF5 at different
time intervals. The in vivo study suggests the formulation MIF4 showed maximum cu-
mulative drug release of 85.0 % and release was sustained up to 10 h. Formulation MIF5
showed 72.1 % cumulative release which was sustained up to 8 h. Also, formulation MIF4
had more tendency to stick to ocular mucosa due to the presence of higher concentration
of quaternary ammonium groups (10 %) in Eudragit RL-100 as compared to Eudragit
RS-100 (5 %). The presence of quaternary ammonium groups renders positive charge to
the polymers by which it can interact with anionic mucin and thereby increase its resi-
dence on corneal surface.

Stability
Finally, accelerated stability studies at elevated temperature and humidity revealed
no significant changes in color in insert formulations. The moxifloxacin concentration in
all formulations at accelerated and room temperature are shown in Fig. 2. The degrada-
tion rate constants (kcal) and shelf life (t90) values for MIF1, MIF3, MIF5–MIF7 at room
temperature were found to range between 2.12 and 1.69 days–1, and 490–617 days. MIF2
and MIF4 showed lower degradation constants of 1.12 and 1.41 day–1 and longer shelf
life of 926 and 739 days, resp. The stability study concluded that formulations MIF2 and
MIF4 showed the lowest degradation and maximum shelf life as per the ICH guidelines
(17) suggest there is no need to add overages to ensure 2 year shelf life.

0.16
0D
0.14

3W
Drug concentration (mg mm –2)

0.12

0.10 6W

0.08
3M

0.06
6M
0.04

0.02

0
T T T T T T T T T T T T T T
1E 1R 2E 2R 3E 3R 4E 4R 5E 5R 6E 6R 7E 7R
IF IF IF IF IF IF IF IF IF IF IF IF IF IF
M M M M M M M M M M M M M M

Fig. 2. Stability of moxifloxacin ocular inserts under accelerated condition and room temperature.
Mean ± SD (n = 3). ET – elevated temperature (40 °C), RT – room temperature, D – days, W – weeks,
M – months.

101
P. K. Pawar et al.: Design and evaluation of moxifloxacin hydrochloride ocular inserts, Acta Pharm. 62 (2012) 93–104.

100

90

80
Cumulative drug release (%)

70

60

50 MIF 4

40
MIF 5
30

20

10

0
0 2 4 6 8 10 12

Time (h)

Fig. 3. In vivo moxifloxacin release profile from ocular inserts.

CONCLUSIONS

In conclusion, we suggest that the ocular insert formulation of moxifloxacin can be

a promising vehicle for topical ocular administration of antibiotics. Its application could
possibly replace the use of fortified solutions of antimicrobials and reduce the necessity
for repeated drug administration at frequent intervals, thereby potentially lowering cor-
neal toxicity and increasing patient compliance.
Acknowledgements. – The authors are thankful to Ranbaxy Laboratories Limited, Gurgaon, In-
dia, for donating the moxifloxacin hydrochloride bulk drug. The authors thank All India Council of
Technical Education (New Delhi, India) for providing a National Doctoral Fellowship to Mr. Pravin
Kondiba Pawar.

REFERENCES

1. E. Barbu, I. Sarvaiya, K. L. Green, T. G. Nevell and J. Tsibouklis, Vinylpyrrolidone-co-(meth)

acrylic acid inserts for ocular drug delivery: synthesis and evaluation, J. Biomed. Mater. Res. 74
(2005) 598–606; DOI: 10.1002/jbm.a.30329.
2. N. Gangopadhyay, M. Daniell, L. Weih and H. Taylor, Fluoroquinolone and fortified antibiotics
for treating bacterial corneal ulcers, Br. J. Ophthalmol. 84 (2000) 378–384; DOI: 10.1136/bjo.84.4.378.
3. A. P. Smith, M. Pennefather, S. B. Kaye and C. A. Hart, Fluoroquinolones: place in ocular ther-
apy, Drugs 61 (2001) 747–761.
4. P. E. Cutarelli, J. H. Lass, H. M. Lazarus, S. C. Putman and M. R. Jacobs, Topical fluoroquinolo-
nes: antimicrobial activity and in vitro corneal epithelial toxicity, Curr. Eye Res. 10 (1991) 557–563;
DOI: 10.3109/02713689109001764.

102
P. K. Pawar et al.: Design and evaluation of moxifloxacin hydrochloride ocular inserts, Acta Pharm. 62 (2012) 93–104.

5. P. L. Mallari, D. J. McCarty, M. Daniell and H. Taylor, Increased incidence of corneal perforation

after topical fluoroquinolone treatment for microbial keratitis, Am. J. Ophthalmol. 131 (2001)
131–133; DOI: 10.1016/S0002-9394(00)00642-5.
6. S. Barath and S. R. Hiremath, Ocular delivery system of perfloxacin mesylate, Pharmazie 54 (1999)
55–58.
7. A. S. Mundada and B. K. Srikhande, Formulation and evaluation of ciprofloxacin hydrochloride
soluble ocular drug insert, Curr. Eye Res. 33 (2008) 469–475; DOI: 10.1080/02713680802023104.
8. G. Di Colo, S. Burgalassi, P. Chetoni, M. P. Fiaschi, Y. Zambito and M. F. Saettone, Gel-forming
erodible inserts for ocular controlled delivery of ofloxacin, Int. J. Pharm. 14 (2001) 101–111; DOI:
10.1016/S0378-5173(02)00421-0.
9. J. M. Woodcock, J. M. Andrews, F. J. Boswell, N. P. Brenwald and R. Wise, In vitro activity of
BAY 12-8039, a new fluoroquinolone, Antimicrob. Agents Chemother. 41 (1997) 101–106.
10. E. Pestova, J. J. Millichap, G. A. Noskin and L. R. Peterson, Intracellular targets of moxaciflo-
xacin: a comparison with other fluoroquinolones, J. Antimicrob. Chemother. 45 (2000) 583–590;
DOI: 10.1093/jac/45.5.583.
11. P. K. Pawar and D. K. Majumdar, Effect of formulation factors on in vitro permeation of moxi-
floxacin from aqueous drops through excised goat, sheep and buffalo corneas, AAPS PharmSci
Tech. 7 (2006) E13.
12. P. K. Pawar and D. K. Majumdar, In vitro permeation characteristics of moxifloxacin from oil
drops through excised goat, sheep, buffalo and rabbit corneas, Pharmazie 62 (2007) 853–857;
DOI: 10.1691/PH.2007.11.7055.
13. M. Malhotra and D. K. Majumdar, In vitro transcorneal permeation of ketorolac tromethamine
from buffered and unbuffered aqueous ocular drops, Indian J. Exp. Biol. 35 (1997) 941–947.
14. L. Perioli, V. Ambrogi, S. Giovagnoli, M. Ricci, P. Blasi and C. Rossi, Mucoadhesive bilayered
tablets for buccal sustained release of flurbiprofen, AAPS PharmSciTech. 8 (2007) E54; DOI:
10.1208/pt0803054.
15. P. Costa and L. J. Manuel Sousa, Modeling and comparison of dissolution profiles, Eur. J. Pharm.
Sci. 13 (2001) 123–133; DOI: 10.1016/S0928-0987(01)00095-1.
16. V. Shankar, A. K. Chandrasekaran, S. Durga, G. Geetha and V. A. Ravichandran, Design and
evaluation of diclofenac sodium ophthalmic inserts, Acta Pharm. Sci. 48 (2006) 5–10.
17. International Conference on Harmonization, Q1A (R2): Stability Testing of New Drug Substances
and Products, ICH, Geneva 2003.

S A @ E TA K

Dizajniranje i vrednovanje okularnih umetaka moksifloksacin hidroklorida

PRAVIN K. PAWAR, RAJESH KATARA i DIPAK K. MAJUMDAR

Cilj rada bio je priprava i evaluacija okularnih umetaka moksifloksacina. Okularni

umetak izra|en je od vodene suspenzije moksifloksacina, natrijevog alginata, polivinil-
nog alkohola i dibutil-ftalata metodom odlijevanja filma. Okularni umetak (promjera 5,5
mm) umre`en je pomo}u CaCl2 i oblo`en Eudragitom S-100, RL-100, RS-100, E-100 ili
Eudragit L-100. In vitro drena`a/permeacija lijeka prou~avana je koriste}i staklenu mo-
dificiranu Franzovu difuzijsku }eliju. Koncentracija lijeka i vrijeme mukoadhezije oku-

103
P. K. Pawar et al.: Design and evaluation of moxifloxacin hydrochloride ocular inserts, Acta Pharm. 62 (2012) 93–104.

larnih umetaka bili su zadovoljavaju}i. Umre`avanje i oblaganje polimerima produljilo

je drena`u iz umetaka. Umre`eni okularni umetci oblo`eni s Eudragit RL-100 pokazali
su ve}u permeaciju lijeka u odnosu na ostale pripravke.

Klju~ne rije~i: moksifloksacin, okularni umetak, kornea koze

Chitkara College of Pharmacy, Chitkara University, Chandigarh-Patiala National Highway, Rajpura,

Rajpura-140401, Patiala, Punjab, India

Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research, (formerly College
of Pharmacy), University of Delhi, Pushp Vihar, Sector III, New Delhi-110017, India

104