1Kamal Singh Rathore*, 2Nema R.K.

,
*1BN Girls College of Pharmacy, Udaipur-
Raj.313002
2Rishiraj College of Pharmacy, Indore-M.P.

kamalsrathore@gmail.com
+919828325713(M)
Eye anatomy
Rule of seven in eye anatomy:
•Weight of both spheres:≈7.0 gm
•Volume of eye: ≈7.0 mL
•Circumference of eye: ≈ 7.0 cm
•Total protein in eye: ≈0.7% w/v
•Total sugar present: ≈0.7% w/v
•Total NaCl present: ≈ 0.7% w/v
•Total mineral elements(Na+, K+.
NH3+): ≈0.7% w/v
•Volume of lachrymal fluid : ≈7.0 μl
•Corneal surface epithelial
intracellular pore size: ≈0.7
nm
•Protein in blood: ≈7.0% w/v
and
•pH of lachrymal fluid (tears): ≈ 7.0
Conventional dosage
forms
The conventional ocular dosage forms for the
delivery of drugs are
Eye drops
Eye ointments
Eye lotion
 Limitations of conventional
dosage forms INSTILLED DOSE

EVAPOPORATION OF TEARS
DRUG-PROTIN
INTERACTION

DRUG PRECORNEAL AREA CORNEAL ABSORPTION

METABOLISM

CONJUNCTIVAL
ABSORPTION

DRINAGE
INDUCED NORMAL TEAR
LACRIMATION TURNOVER

Fig.No-2 Elimination of Instilled via Different routes

 The recent trends in
ophthalmic drug delivery
Mucoadhesive dosage forms:
Phase Transition systems: in-situ gelling
Ocular Inserts or films: SODI, NODS, Lacrisert, BODI, Dry
drops and gelfoams, minidiscs
Collagen shields
Drug presoaked hydrogel type contact lens and pledgets
Ocular Iontophoresis (Pulsatile drug delivery)
Chemical delivery systems vesicular systems:
Microspheres, microparticles, Nanoparticles, liposomes,
niosomes, and PEGylation, dendrimers
exhibited by conventional
ophthalmic solutions due to
rapid precorneal elimination
of the drug may be
overcome by the use of in
situ gel-forming systems
that are instilled as drops
into the eye and undergo a
sol–gel transition in the cul-
de-sac.
IN-SITU SYSTEM

In-situ: at the place

Improved local bioavailability
Reduced dose concentration
Less total drug
Improved patient acceptability
Reduced dosing frequency
Advantages of in-situ
forming gel:
 Generally more comfortable than insoluble or soluble insertion
 Less blurred vision as compared to ointment
 Increased bioavailability due to –
 Increased precorneal residence time
 Decreased nasolacrimal drainage of the drug
 Chances of undesirable side effects arising due to systemic
absorption of the drug through naso-lacrimal duct is reduced
 Drug effect is prolonged hence frequent instillation of drug is not
required
 The carbomer polymeric gel base itself has been used
successfully to treat moderate to severe cases of dry eye such
as Keratoconjuctivitis Sicca.
 In-situ gelling system
In situ-forming hydrogels are liquid upon
instillation and undergo phase transition in the
ocular cul-de-sac to form visco-elastic gel and
this provides a response to environmental
changes.
ISGS three methods:-
Change in pH
Change in temperature
Ion activation
 Change in
temperature
Sustained drug delivery can be achieved by
use of a polymer that changes from sol to gel
at the temperature of the eye. Temperature
dependent systems include pluronics and
tetronics. The poloxamers F127 are polyols
with thermal gelling properties whose solution
viscosity increases when the temperature is
raised to the eye temperature (32-34°C) from
a critical temperature (16°C).
 Change in pH
 pH triggered systems show sol to gel transformation when the pH
is raised by the tear fluid to pH 7.4. pH triggered systems include-
cellulose acetate hydrogen phthalate latex, (pH 5.0 to 7.2-7.4 forms a gel with
LF).
Carbopol (polyacrylic acid 0.5%, polycarbophil) pH 4.0 to 7.4 sol to gel
transformation
 Cellulose acetophthlate (CAP) is a polymer with potentially useful
properties for sustained drug delivery to the eye, since latex is a
free flowing solution at a pH of 4.4 which undergoes coagulation
when the pH is raised by the tear fluid of pH 7.4.
 pH triggered in-situ gelling system are low viscosity polymeric
dispersion in water which undergoes spontaneous coagulation and
gelation after instillation in conjuctival cul-de-sac.
 Change in electrolyte
composition
Ion activated system show sol to gel transformation in
the presence of the mono or divalent cations (Na+, Ca2+
etc.)typically found in the tear fluids.
Ion activated system include Gelrite® (Gomme gellan)
and alginates. Gellan gum is an anionic extracellular
polysaccharide secreted by Pseudomonas elodea. Gellan
gum formulated in aqueous solution, forms clear gels in
the presence of the mono or divalent cations.
These system shows sol to gel transformation in the
presence of ions.
 Drug Formulation approach
Polymers/Bases Reference(s)
 Indomethacine In-situ Gelling System
 Pefloxacin mesylate In-situ Gelling System Gellan Gum
 Pilocarpine In-situ Gelling System
 Carteolol In-situ Gelling System
 Gatifloxacin In-situ Gelling System
 Ofloxacin In-situ Gelling System
 Ciprofloxacin In-situ Gelling System
 Pilocarpine In-situ Gelling System
 Pilocarpine In-situ Gelling System
 Pilocarpine In-situ Gelling System
 Timolol in-situ gelling system
Gellan Gum (Balasubramaniam Et Al., 2003)
(Sultana et al., 2006a)
Alginate (Cohen Et Al., 1997)
Alginate (Demailly Et Al., 2001)
Alginate/HPMC (Liu Et Al., 2006)
Carbopol® 940/HPMC (Srividya Et Al., 2001)
Poloxamer/Hyaluronic Acid (Cho Et Al., 2003)
Pluronic F127, MC, HPMC (Desai & Blanchard, 1998)
Pluronic F127/Carbopol (Lin & Sung, 2000)
Pluronic F127, Xyloglucan (Miyazaki Et Al., 2001)
Pluronic F127, CMC, HPMC (El-Kamel, 2002)
Conclusion
In-situ gel offers-easy, accurate and
reproducible administration of a dose,patient
compliance, effective alternative to conventional
dosage form,
can easily be instilled in liquid form, but are
capable of prolonging the residence time of the
formulation on the surface of the eye
ability to release drug in sustained manner,
assist enhancing ocular bioavailability, flexibility
in design system with desirable rheological
properties and drug release rate.
References

 Liu Z; Pan W; Nie S; Zhang L; Yang X; Li J, Preparation and evaluation of sustained

ophthalmic gel of enoxacin Drug Dev Ind Pharm. 2005; 31(10):969-75
 Balasubramaniam J; Pandit JK, Ion-activated in situ gelling systems for sustained ophthalmic
delivery of ciprofloxacin hydrochloride. Drug Deliv. 2003; 10(3):185-91.
 Liu Z; Li J; Nie S; Liu H; Ding P; Pan W, Study of an alginate/HPMC-based in situ gelling
ophthalmic delivery system for gatifloxacin. Int J Pharm. 2006; 315(1-2):12-7
 Kaur IP; Kanwar M., Ocular preparations: the formulation approach. Drug Dev Ind Pharm.
2002; 28(5):473-93
 Srividya B; Cardoza RM; Amin PD, Sustained ophthalmic delivery of ofloxacin from a pH
triggered in situ gelling system. J Control Release. 2001; 73(2-3):205-11
 Sultana Y; Aqil M; Ali A; Zafar S, Evaluation of carbopol-methyl cellulose based sustained-
release ocular delivery system for pefloxacin mesylate using rabbit eye model. Pharm Dev
Technol. 2006; 11(3):313-9
 Balasubramaniam J; Kant S; Pandit JK, In vitro and in vivo evaluation of the Gelrite gellan
gum-based ocular delivery system for indomethacin Acta Pharm. 2003;53(4):251-61
 El-Kamel AH, In vitro and in vivo evaluation of Pluronic F127-based ocular delivery system
for timolol maleate.Int J Pharm. 2002; 241(1):47-55
THANK
YOU