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OPHTHALMIC IN-SITU GEL: AN OVERVIEW
Pallavi R. Kute1*
, S B. Gondkar2 and R B.Saudagar
3
1*
Department of Quality Assurance Techniques, R. G. Sapkal College of Pharmacy, Anjaneri,
Nashik-422213, Maharashtra, India.
2Department of Pharmaceutics, R.G.Sapkal, College of Pharmacy, Anjaneri, Nashik-422213,
Maharashtra, India.
3Department of Pharmaceutical Chemistry, R.G. Sapkal College of Pharmacy, Anjaneri,
Nashik-422213, Maharashtra, India.
ABSTRACT
Ocular drug delivery has been a major challenging and interesting field
for the pharmaceutical scientists due to unique anatomy and
physiology of eye.The major problem encountered in ocular drug
delivery is the rapid loss of the drug through lachrymal drainage which
results in poor bioavailability and therapeutic response of the
drug.There are some static(different layers of the eye
i.e.cornea,sclera,retina) and dynamic(blood aqueous and blood retinal
barrier) barriers which also affect the bioavailability of the drug. In-situ
gels are the liquid preparations which upon instillation undergoes
phase transition in cul-de-sac of the eye to form a viscous gel and this
occurs due to the environmental changes in the eye(i.e.due to change in
temperature, change in pH and ion induced change). This review is to
specify the basic anatomy and physiology of human eye, various
approaches used for formulation of in-situ gels and polymers used in the formulation of in-
situ gels.
KEYWORDS: In situ gel,biodegradable polymers,pH sensitive,temperature sensitive,ion
sensitive.
INTRODUCTION
Eye is the most vital organ of the body.[1]
It is the sensory organ that converts light to an
electric signal that is treated and interpreted by the brain.[2]
Ophthalmic drug delivery is the
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Article Received on
21 Jan 2015,
Revised on 15 Feb 2015,
Accepted on 11 March 2015
*Correspondence for
Author
Pallavi R. Kute
Department of Quality
Assurance Techniques, R.
G. Sapkal College of
Pharmacy, Anjaneri,
Nashik-422213, Maha-
rashtra, India.
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challenging endeavor faced by the pharmaceutical researchers today.The structural and
functional aspects of the eye render this organ highly impervious to foreign substances.[3]
In
the earlier period,drug delivery to the eye has been limited to topical
application,redistribution into the eye following systemic administration or direct
intraocular/per ocular injections.[4]
But the conventional ocular drug delivery systems like
solutions,suspensions and ointments show drawbacks such as increased precorneal
elimination,high variability and blurred vision.[1]
So to overcome the problems caused by
these conventional dosage forms and to improve the ocular bioavailability,recently there are
considerable efforts directed towards controlled and sustained drug delivery in modern
pharmaceutical field.[5]
Ophthalmic in-situ gel is one of those efforts undertaken by the
pharmaceutical researchers.
OVERVIEW OF ANATOMY AND PHYSIOLOGY OF HUMAN EYE
The eye is most important organ of human body. The cornea, lens, and vitreous body are
transparent media with no blood vessels. Oxygen and nutrients are transported to these
nonvascular tissues by the aqueous humour. The aqueous humour has a high oxygen tension
and about the same osmotic pressure as blood. The cornea also derives part of its oxygen
need from the atmosphere and is richly supplied with free nerve endings. The transparent
cornea is continued posterior into opaque white sclera, which consists of tough fibrous tissue.
Both cornea and sclera withstand the intra-ocular tension constantly maintained in the eye.
The eye is constantly cleansed and lubricated by the lachrymal apparatus, which consists of
four structures: Lachrymal glands, lachrymal canals, lachrymal sac, naso- lachrymal duct.
The lachrymal fluid secreted by the lachrymal glands is emptied on the surface of the
conjunctiva of the upper eyelid at a turnover rate of 16% per min. It washes over the eyeball
and is swept up by the blinking action of the eyelids. Thus the eyeball is continually irrigated
by a gentle stream of lachrymal fluid that prevents it from becoming dry and inflamed. The
lachrymal fluid in humans has a normal volume of 7µl and is an isotonic aqueous solution of
bicarbonate and sodium chloride (pH 7.4) that serves to dilute irritants or to wash the foreign
bodies out of the conjunctival sac. It contains lysozyme, whose bactericidal activity reduces
the bacterial count in the conjunctival sac. The rate of blinking varies widely from one person
to another, with an average of approximately 20 blinking movements per min. During each
blink movement the eyelids are closed for a short period of about 0.3 sec.[1]
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Fig. 1 Anatomy of Eye
FATE OF THE FORMULATION ADMINISTERED THROUGH OCULAR ROUTE[1]
At first sight, the eye seems an ideal, easily accessible target organ for topical treatment.
However, the eye is, in fact, well protected against absorption of foreign materials, first by
eyelids and tear‐flow and then by the cornea, which forms the physical‐ biological
barrier.When any foreign material or medication is introduced on the surface of the eye, the
tear-flow immediately increases and washes it away in a relatively short time. Under normal
conditions, the eye can accommodate only a very small volume without overflowing. This
anatomy, physiology and biochemistry of the eye are responsible for the low bioavailability
of drug. The challenge is to overcome these protective barriers of the eye without causing
permanent tissue damage.
Fig. 2 Fate of the formulation administered through eye
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VARIOUS PROBLEMS ENCOUNTERED IN POOR BIOAVAIBILITY OF DRUGS
INSTILLED THROUGH EYE[1,2,6,7]
• Binding by the lachrymal proteins.
• Drainage of the instilled solutions.
• Lachrimation and tear turnover.
• Limited corneal area and poor corneal penetration.
• Non‐productive absorption/adsorption.
CHARACTERISTICS REQUIRED TO OPTIMIZE DRUG DELIVERY SYSTEMS[1,5]
• Good corneal penetration.
• Prolonged contact time with corneal tissue.
• Simplicity of installation for the patient.
• Non- irritative and comfortable form (the viscous solution should not provoke Lachrimation
and reflex blinking).
IN-SITU GELLING SYSTEM
A more desirable dosage form would be one that can deliver drug in a solution form, create
little to no problem of vision and need be dosed no more frequently than once or twice daily.
In situ activated gel forming systems are those which are when exposed to physiological
conditions will shift to a gel phase. This new concept of producing a gel in situ was suggested
for the first time in the early 1980s. Gelation occurs via the cross-linking of polymer chains
that can be achieved by covalent bond formation (chemical cross-linking) or non-covalent
bond formation (physical cross-linking). In situ gel-forming systems can be described as low
viscosity solutions that undergo phase transition in the conjunctival cul-de-sac to form
viscoelastic gels due to conformational changes of polymers in response to the physiological
environment. The rate of in situ gel formation is important because between instillation in the
eye and before a strong gel is formed, the solution or weak gel is produced by the fluid
mechanism of the eye.[8]
Both natural and synthetic polymers can be used for the production
of in situ gels.[1]
ADVANTAGES OF IN-SITU FORMING GEL[1]
Less blurred vision as compared to ointment.
Decreased nasolacrimal drainage of the drug which may cause undesirable side effects
due to systemic absorption (i.e. reduced systemic side effects).
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The possibility of administering accurate and reproducible quantities, in contrast to
already gelled formulations and moreover promoting precorneal retention.
Sustained, Prolonged drug release and maintaining relatively constant plasma profile.
Reduced number/frequency of applications hence improved patient compliance and
comfort.
Generally more comfortable than insoluble or soluble insertion.
Increased bioavailability due to increased precorneal residence time and absorption.
REQUIREMENT OF IDEAL SYSTEM[1]
Ideally, an In- situ gelling system should be a low viscous, free flowing liquid to allow for
reproducible administration to the eye as drops and the gel formed following phase transition
should be strong enough to with stand the shear forces in the cul-de-sac and demonstrated
long residence times in the eye with its ability to release drugs in sustained manner will assist
in enhancing the bioavailability, reduce systemic absorption and reduce the need for frequent
administration leading to improved patient compliance.
APPROACHES FOR IN-SITU GELLING SYSTEM
A new approach is to try to combine advantages of both solutions and gels, such as accuracy
and ease of administration of the former and prolonged residence time of the latter. Thus, in
situ hydrogels can be instilled as eye drops and undergo an immediate gelation when in
contact with the eye. In situ-forming hydrogels are liquid upon instillation and undergo phase
transition in the ocular cul-de-sac to form viscoelastic gel and this provides a response to
environmental change.[9]
The main approaches for in-situ gelling system can be classified as
follows.
A) Physiological stimuli approach[1]
or Stimuli-responsive in situ gel systems[10]
This approach is further subclassified as.
a.Temperature induced in-situ gelling system.
b.pH induced in-situ gelling systems.
B) Physical change in biomaterial approach[1]
This approach can be further subclassified as:
a.Swelling mechanism.
b.Diffusion mechanism.
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C) Chemical reaction approach[1]
or Chemically induced in situ gelling system[10]
This approach can be further subclassified as:
a.Ionic cross linking.
b.Photo-polymerisation.
c.Enzymatic cross-linking.
Above mentioned approaches for in-situ gels can be explained in detail as follows.
A) Physiological stimuli approach or stimuli-responsive in-situ gel systems.
Stimuli responsive polymers are defined as polymers that undergo relatively large and abrupt
physical or chemical changes in response to small external changes in the environmental
conditions.[10]
a. Temperature induced in situ gelling system
Temperature is the most widely used stimulus in environmentally responsive polymer
systems as it is easy to control whenever needed and it is applicable to both in vitro and in
vivo systems.[10]
The ideal critical temperature for this system is ambient and physiologic
temperature.[1]
In these systems,gelling of the solution is triggered by change in
temperature,thus sustaining the drug release.[1,10]
These hydrogels are liquid at room
temperature(20-25ºC) and undergo gelation when in contact with body fluids(35-37ºC) due to
change in temperature.[1,10,11]
Temperature sensitive gels are of three types:positive
temperature sensitive gel,negative temperature sensitive gel and thermally reversible gel.
Negative temperature sensitive gels have Lower Critical Solution Temperature(LCST),such
gels contracts on heating above LCST.Positive temperature sensitive gel has Upper Critical
Solution Temperature(UCST),such gels contracts on cooling below UCST.[11]
Mechanism[11]
In this system,the sol-gel phase transition due to increase in temperature occurs mainly by
three mechanisms-Desolvation of the polymer,increased micellar aggregation and increased
entanglement of polymeric network.As the temperature increases polymeric chain degrades,
which leads to the formation of hydrophobic domain and phase transition(liquid to hydrogel)
occurs.
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Fig.3 Mechanism of Temperature sensitive in situ gelling system
b.pH induced in-situ gel systems
Polymers containing acidic or alkaline functional groups that respond to changes in pH are
called pH sensitive polymers.[10]
In this system,sol to gel transition takes place when pH is
raised from 4.2 to 7.4(eye pH).At higher pH,polymer forms hydrogen bonds with mucin
which leads to hydrogel formation.[1,11]
Mechanism
All the pH sensitive polymers contain pendant acidic or basic groups that can either accept or
release protons in response to changes in environmental pH.[1,11]
The polymers with a large
number of ionisable groups are known as polyelectrolytes.[10]
Swelling of polymer increases
as the external pH increases in the case of weakly acidic(anionic) groups,also known as
polyacids,but decreases if polymer contains weakly basic(cationic) groups termed as
polybases.[1,10,11]
Fig.4 Mechanism of pH sensitive in situ gelling system
B) Physical change in biomaterial approach
a.Swelling mechanism
In this approach,in-situ gel is formed when material absorbs water from surrounding
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environment and expand to occur desired space.One such substance is myverol(glycerol
mono-oleate),which is polar lipid that swells in water to form lyotropic liquid crystalline
phase structures.[1,12]
b.Diffusion mechanism
This method involves the diffusion of solvent from polymer solution into surrounding tissue
and results in precipitation or solidification of polymer matrix.N-
methylpyrrolidone(NMP),dimethylsulfoxide(DMSO),tetrahydrofuran,2 pyrrolidone and
triacetin has been shown to be useful solvents for such system.
C) Chemical reaction approach
Ionic cross linking-Certain ion sensitive polysaccharides undergo phase transition presence of
various ions such as K+,Ca
2+,Mg
2+,Na
+.These polysaccharides fall into the class of ion-
sensitive ones.[1]
Mechanism
Gelation occurs by ionic interaction of polymer and divalent ions of tear fluid.When anionic
polymers come in contact with cationic ions,it converts to form gel.[11]
Fig.5 Mechanism of ion sensitive in situ gelling system.
b.Photo-polymerisation
A solution of monomers or reactive macromer and initiator can be injected into a tissue site
and to this site electromagnetic radiation is applied due to which the gel is formed.Acrylate or
similar polymerizable functional groups are typically used as the polymerizable groups on the
individual monomers and macromers because they rapidly undergo photo polymerization in
the presence of suitable photo initiator.Photopolymerizable systems when introduced to the
desired site via injection get photocured in situ with the help of fiber optic cables and then
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release the drug for prolonged period of time.[1]
b. Enzymatic cross-linking
This approach is still under investigation as natural enzymes are responsible for forming the
in-situ gel.But it is estimated that this method will be more advantageous than chemical and
photochemical approaches.For example,intelligent stimuli-responsive delivery systems using
hydro gels that can release insulin have been investigated.[1]
POLYMERS USED IN THE FORMULATION OF IN-SITU GELS
Definition
A polymer is a large molecule (macromolecule) composed of repeating structural units.These
subunits are connected by covalent chemical bonds.[13]
Ideal characteristics of polymers[14]
The polymers used for in-situ gelling systems should have following characteristics:
It should be biocompatible.
It should be capable of adherence to mucus.
It should have pseudo plastic behaviour.
It should be tolerable.
It should have good optical activity.
It should influence the tear behaviour.
The polymer should be capable of decreasing viscosity with increasing shear rate there by
offering lowered viscosity during blinking and stability of tear film during fixation.
The polymers used in in-situ gels can be explained in detail as follows
1.CARBOPOL
It is a pH sensitive polymer.It is also called as carbomer,acritamer,acrylic acid polymer,etc.[15]
Structure of Carbopol[11]
Fig.6 Structure of Carbopol
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Properties of Carbopol[11]
1) Carbomer is a high molecular weight, cross linked polyacrylic acid derivative and has
strongest mucoadhesive property.
2) It is a water soluble vinyl polymer.
3) In aqueous solution, it shows sol to gel transition, when the pH is raised above its pKa
value of about 5.5.
4) As the concentration of carbomer increases, its acidic nature may cause irritation to
eye.Addition of cellulose will reduce polymer concentration and will also improve gelling
property.
Table no.1: Various grades of carbopol[11]
GRADE CROSS-LINKING DENSITY
Carbopol 934 Lowest
Carbopol 940 Highest
Carbopol 981 Intermediate
Table no.2: Uses of Carbopol[15]
USE CONCENTRATION (%)
Gelling Agent 0.5-2.0
Emulsifying Agent 0.1-0.5
Suspending Agent 0.5-1.0
Mechanism
Mucoadhesive property is due to four mechanisms of interaction between mucin and poly
(acrylic acid)-electrostatic interaction,hydrogen bonding,hydrophobic interaction and
interdiffusion.[9]
Carbopol molecule is tightly coiled acidic molecule. Once dispersed in
water, carboxylic group of the molecule partially dissociates to form flexible coil. Being a pH
sensitive polymer, increase in solution pH results swelling of polymer. In acidic medium, it is
in collapsed state due to hydrogen bonding, as the pH increases, electrostatic repulsion occur
between the anionic groups, results gel swelling. The gelling effect is activated in two
stages:dispersion and hydration of carbopol, neutralizing the solution by addition of sodium
hydroxide,Triethanolamine, or potassium hydroxide.[11]
2.POLOXAMER
It is a temperature sensitive polymer.It is commercially called as Pluronic.®
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Structure of poloxamer
Fig.7 Structure of poloxamer
Properties of Poloxamer
1) It is a water soluble tri-block copolymer consisting of two polyethylene oxide(PEO) and
polypropylene oxide(PPO) core in an ABA configuration.
2) PPO is the hydrophobic central part which is surrounded on both sides by hydrophilic
PEO.
3) It has good thermal setting property and increased drug residence time.
4) It gives colourless,transparent gel.[11]
5) Concentrated aqueous solutions of Poloxamer form thermoreversible gels.[9]
Table no.3: Various grades of poloxamer[11]
POLOXAMER MOLECULAR WEIGHT
124 2200
188 8400
237 7959
338 14600
407 12600
Uses of Poloxamer
a) Gelling Agent.
b) Emulsifying Agent.
c) Solubilizing Agent.
Mechanism
At room temperature (25ºC), it behaves as viscous liquid and is transformed to transparent gel
when temperature increases (37ºC). At low temperature, it forms small micellar subunit in
solution and increase in temperature results increase in viscosity which leads to swelling to
form large micellar cross linked network.
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Fig.8 Gelling mechanism of Poloxamer
3.GELLAN GUM
It is an ion-sensitive polymer.It is also known as Gelrite®(trade name).
Structure of gellan gum
Fig.9 Structure of Gelrite
Properties of Gellan Gum
1) Gellan gum is a linear,anionic heteropolysaccharide secreted by the microbe
Sphingomonas elodea.[9,11]
2) The backbone of the polymer consists of glucose,glucoronic acid and rhamnose in the
molar ratio 2:1:1.These are linked together to give a tetrasaccharide repeat unit.
3) Gelrite is deacetylated gellan gum, obtained by treating gellan gum with alkali to remove
the acetyl group in the molecule.
4) Upon instillation, gelrite forms gel due to the presence of calcium ions.
5) The gelation involves the formation of double helical junction zones followed by
aggregation of double helical segment to form three dimensional networks by
complexaton with cations and hydrogen bonding with water.
6) It is widely used in ophthalmology because of its thixotropy,thermo plasticity and pseudo
plasticity.
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Uses of Gellan Gum
a) Thickening Agent.
b) Gelling Agent.
c) Stabilizing Agent.
Mechanism
Gellan gum produce a cation induced in situ gelation (Ca2+, Mg 2+, K+, Na+) due to the
cross linking between negatively charged helices and mono or divalent cations (Na+, Ca+,
Mg+). Divalent ions are superior in promoting gelation as compared to monovalent cations.
Gelation prolongs the residence time of drug at absorption site and bioavailability of the drug
is increased.
4.SODIUM ALGINATE
It is an ion-sensitive polymer.It is also known as algin,alginic acid,sodium
salt,E401,Kelcosol,Keltone,Protanal,sodium polymannuronate.[15]
Properties of Sodium Alginate[11]
1) Sodium alginate is a gum extracted from brown algae.
2) It is a salt of alginic acid.
3) It is a linear block polysaccharide consisting of two types of monomers-β-D-Mannuronic
acid and α-L-glucouronic acid residues joined by 1,4-glycosidic linkages.
4) It exhibits good mucoadhesive property due to presence of carboxylic group.
5) It is biodegradable and non-toxic.
6) It has high molecular weight of 20 to 600 kDa.[13]
Structure of Sodium Alginate
Fig.10 Structure of Sodium Alginate
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Uses of Sodium Alginate[15]
a) Thickening Agent.
b) Suspending Agent.
Mechanism[11]
The monomers of alginate (β-D-mannuronic acid (M) and α-L- glucuronic acid (G) are
arranged as M-M block or G-G block with alternating sequence (M-G) block. Upon
interaction of G block of polymer with calcium moieties, formation of homogenous gel takes
place.Mechanical strength and porosity of hydrogel depends on G: M ratio,type of cross
linker used and concentration of alginate solution.
5.CHITOSAN
Structure of Chitosan[11]
Fig.11 Structure of Chitosan
Properties of Chitosan
1) Chitosan is a cationic polysaccharide which consists of copolymers of glucosamine and
N-acetyl glucosamine,these are natural polymer obtained by deacetylation of chitin.[11]
2) Chitosan has mucoadhesive property due to electrostatic interactions between positively
charged amino group and negatively charged mucin.[11]
3) It is a polycationic polymer and also called as ophthalmic vehicle.[16]
4) It is biodegradable,biocompatible and non-toxic polymer.[16]
5) It exhibits pseudoplastic and viscoelastic behaviour.[16]
6) It has good antibacterial and bioadhesive property.[11,16]
7) It has ability to convert into hydrogel at ocular pH(pH 7.4).[17]
Mechanism
The mucoadhesive property is due to the formation of ionic interaction between the
positively charged amino groups of chitosan and negatively charged sialic acid residues of
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mucin.Because of its bioadhesive, hydrophilic, good spreading properties,it is used as
viscosifying agent in artificial tear formulations.
6.HYDROXYPROPYL METHYL CELLULOSE
It is a temperature sensitive polymer.It is also known as Hypromellose,Methocel,etc.[15]
Structure of HPMC[11]
Fig.12 Structure of HPMC
Properties of HPMC
1) It is a water soluble cellulose ether.[18]
2) The reasons for widespread acceptance of HPMC include-[19]
a) Solubility characteristics of the polymer in organic and aqueous solvent system.
b) Non-interference with drug availability.
c) Flexibility and absence of taste and odour.
d) Stability in the presence of heat,light,air or reasonable levels of moisture.
3) It is composed of glucan chain with repeating β-(1,4)-D-glucopyranose unit.[11]
4) It increases its viscosity when temperature increases.[11]
5) At low concentrations(1-10 wt.%) aqueous solutions of HPMC are liquid at low
temperature but gel upon heating.[20]
6) It shows phase transition between 75ºC and 90ºC.These phase transition temperatures can
be lowered by chemical or physical modifications.[20]
7) By reducing the hydroxyl propyl molar substitution of HPMC,its transition temperature
can be lowered to 40⁰C.’
Uses of HPMC[15]
a) Thickening Agent.
b) Suspending Agent.
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c) Stabilizing Agent.
Table no.4: Commercial grades of HPMC[20]
POLYMER GRADE VISCOSITY
(mPas) pH
Hydroxypropyl
Methyl cellulose Methocel
5.5-8.0 for a 1% w/v
aqueous solution
A4MP 4000
A15-LV 15
A15CP 1500
A4CP 400
Mechanism[20]
Gelation of HPMC solutions is primarily caused by the hydrophobic interaction between
molecules containing methoxy substitution. At low temperatures, the macromolecules are
hydrated, and there is little polymer– polymer interaction other than simple entanglement. As
the temperature is raised, the polymers gradually lose their water of hydration, which is
reflected by a decline in relative viscosity. Eventually, when sufficient but not complete
dehydration of the polymer occurs, polymer–polymer associations take place, and the system
approaches an infinite network structure, as reflected experimentally by a sharp rise in
relative viscosity. This sol–gel transformation has been exploited to design in situ gelling
systems. These systems exhibited low viscosity at 23 °C and formed soft gels at 37ºC.
Table no.5: List of Polymers used in in-situ gelling system[11]
POLYMER ORIGIN CHARGE SOLUBILITY MUCOADHESIVE
CAPACITY
Carbomer Synthetic Anionic Insoluble +++
Polyacrylic acid Natural Anionic Insoluble +++
Chitosan Natural Cationic Soluble ++
Xanthan Gum Natural Anionic Insoluble +
Methyl cellulose Natural Non-ionic Soluble +
Xyloglucan Natural Anionic Soluble +
Poloxamer Synthetic Non-ionic Soluble ++
Sodium Aginate Natural Anionic Soluble ++
HPMC Natural Non-ionic Soluble +
[Mucoadhesive Capacity: Excellent(+++),Good(++),Poor(+)]
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Table no.6: List of drugs used with their mechanism of gelation
DRUG USED MECHANISM
OF GELATION POLYMER USED REFERENCE
Brimonidine Tartrate Temperature
dependent
Poloxamer 407 &
HPMC E50LV [21]
Brimonidine Tartrate Thermosensitive Poloxamer 407 &
Chitosan [22]
Gatifloxacin pH triggered Carbopol 940
&HPMC K15M [23]
Gatifloxacin Ion-activated Sodium Alginate
&Methocel E50LV [26]
Lomefloxacin HCl pH induced
Carbopol 940,HPMC
E50LV & HPMC
E4M
[24]
Azithromycin Thermoreversible
Poloxamer
407,HPMC K100
Lvp &PVP K30
[25]
Ofloxacin Ion-activated Gellan gum [27]
Ketorolac
Tromethamine Ion-activated Gelrite
[28]
Naphazoline
Hydrochloride pH induced
Carbopol 940 &
HPMC K4M [29]
Antazoline Phosphate pH induced Carbopol 940 &
HPMC K4M [30]
Table no.7: Marketed Products of In situ Polymeric System[1,5,12,31]
PRODUCT NAME DRUG USED MFG.COMPANY
Timoptic-XE Timolol maleate Merck and Co.Inc.
Regel depot-technology Macromed
Cytoryn Interleukin-2(IL-2) Macromed
Azasite Azithromycin InSite Vision
Pilopine HS Pilocarpine hydrochloride Alcon Laboratories Inc.
AktenTM
Lidocaine hydrochloride Akten
Virgan Ganciclovir Spectrum Thea Pharmaceuticals
CONCLUSION
In-situ gelling systems have been proved advantageous over other conventional dosage
forms. These advantages include sustained and prolonged release of drug, good stability,
biocompatibility, ease of instillation, etc. Polymers used in in-situ gelling systems also play
an important role. Various natural, synthetic, semi synthetic polymers are being used by the
pharmaceutical researchers for controlled release of drug. These polymers are very useful in
the formulation of in-situ gel systems. Moreover,in situ gels have ease of commercialization
which adds advantage from industrial point of view.
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