Dr. V. S. Kashikar Ophthalmic drug delivery is one of the most challenging endeavor facing the pharmaceutical scientists. The anatomy, physiology and biochemistry of the eye render this organ highly impervious to foreign substance. Rapid and efficient drainage by the nasolacrimal apparatus, noncorneal absorption and the relative impermeability of the cornea to both hydrophilic and hydrophobic molecules, all account for such poor ocular bioavailability. Thus to increase the ocular bioavailability of drug, we need to increase the ocular residence time of the drug.

1. Dr. V. S. Kashikar
HOD, Pharmaceutics
PES Modern College of Pharmacy (ladies), Moshi ,Pune
FORMULATION DEVELOPMENT AND EVALUATION OF
SUSTAINED RELEASED OPHTHALMIC FORMULATION
1

2.  Ophthalmic drug delivery is one of the most challenging endeavor
facing the pharmaceutical scientists. The anatomy, physiology and
biochemistry of the eye render this organ highly impervious to
foreign substance.
 Rapid and efficient drainage by the nasolacrimal apparatus,
noncorneal absorption and the relative impermeability of the cornea
to both hydrophilic and hydrophobic molecules, all account for such
poor ocular bioavailability. Thus to increase the ocular
bioavailability of drug, we need to increase the ocular residence
time of the drug.
INTRODUCTION
2

3. To develop a formulation
to reduce the frequency of
administration using the
concept of In situ gelling
system.
Increased residence time in
the eye
Increased Bioavailability
Low dose required
IMPROVED
COMPLIANCE
RATIONALE
3

4. Liquid Drops Gel
pH Temperature Ions Combination
Carbomer Poloxomer Gellan gum of polymers
Chitosan HPMC, MC Alginate
IN SITU GELLING SYSTEMS
4

5. Drug name Brand name
Timolol
maleate
Timoptic Xe
Timolol
maleate
Timolol GFS
Ketorolac
tromethamine
Acular
Indomethacin Indophthal
Ganciclovir Virgan®
MARKETED FORMULATIONS
5

6. Preformulation
Study
Selection of
excipients
Thermosensitive
Selection of optimized
concentration for
gelation
Ion sensitive pH sensitive
PLAN OF WORK
Drug
FORMULATION
DEVELOPMENT
6

7. EVALUATION
Physicochemical
characteristics
Mucoadhesion
potential
In vitro drug release
and transcorneal
permeation study
Rheologica
l behaviour
OPTIMIZATION OF
GELLING SYSTEMS
Antimicrobial
efficiency and
Isotonicity
Ocular
irritation study
And Gamma
Scintigraphy
Study
In vivo study
Stability
studies
7

8. In situ gelling ophthalmic placebo formulations
I) PHASE TRANSITION BASED ON TEMPERATURE
Combinations of Poloxamer 407 and Poloxamer 188 which undergoes
transition from sol to gel at physiological temperature (33-34oC) were
selected to form in situ gelling ophthalmic solutions with the aid of
mucoadhesive polymer, HPMC K4M and chitosan as a penetration
enhancer.
 Poloxamer 407 and Poloxamer 188 and HPMC K4M
 Poloxamer 407, Poloxamer 188, HPMC K4M and Chitosan
II) PHASE TRANSITION BASED ON ION
Alginates and Gellan gum are known to undergo transition from sol to gel
in the presence of cations present in tear fluid (Ca+2, Na+), hence selected to
form in situ gelling ophthalmic solutions with the aid of mucoadhesive
polymers.
 Sodium alginate and HEC/ HPMC K4M
 Gellan gum 8

9. III) PHASE TRANSITION BASED ON PH
Carbopols are known to undergo transition from sol to gel in
the presence of higher pH of tear fluid, hence were selected
to form in situ gelling ophthalmic solutions with the aid of
mucoadhesive polymer, HPMC K4M. Carbopol 974 P was
selected as it is a benzene free grade of carbopol.
 Carbopol 974 P and HPMC K4M
9

10. Combination of sodium alginate and HPMCK4M/ HEC studied
Sr. No.
Sodium
alginate
(% w/v)
HPMCK4M
(% w/v)
HEC
(% w/v)
Sterile
water
Gelling
capacity
Clarity
1 1 -
q.s. to
make
100
ml
+ ++
2 1.5 - ++ ++
3 2 - ++ -
4 1.5 0.2 - +++ ++
5 1.5 0.4 - +++ ++
6 1.5 - 1 +++ ++
7 1.5 - 1.5 +++ ++
8 1.5 - 2 +++ ++
Note: (-) turbid, (+) slightly turbid, (++) clear solution, (+++) clear and transparent
10

11. Gallen gum in situ gelling systems without mucoadhesives studied
Sr.No.
Gellan gum
(% w/v)
Gelling
capacity
Clarity
1 0.1 ++ +++
2 0.2 ++ +++
3 0.3 +++ +++
4 0.4 +++ +++
5 0.5 +++ +++
11

12. Combination of Carbopol 974P and HPMCK4M studied
Sr..
No.
Carbopol
974P
(%w/w)
HPMC K4M
(%w/w)
Citrophosphate
buffer pH 6
Gelling capacity Clarity
1 0.1 1
q.s. to make
100 ml
+ ++
2 0.2 1 ++ ++
3 0.3 1 +++ ++
4 0.4 1 +++ ++
5 0.5 1 +++ ++
12

13. Representative ocular contact of an in-situ gel with sequential pictures
and time activity curve
13

14. Static whole body image after 2 h of drug administration (A) marketed eye drop
solution of Ofloxacin (B) optimized in-situ gel system.
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