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In situ is a Latin phrase which translated literally as

' In position In situ gel is drug delivery systems that are in sol form before administration in the body, but once administered, undergo gelation in situ, to form a gel Administration route for in situ gel oral, ocular, rectal, vaginal, injectable and intraperitoneal routes

Advantages of in situ forming polymeric delivery systems:

Ease of administration

Improved local bioavailability

Reduced dose concentration Reduced dosing frequency,

improved patient compliance and comfort.

Its production is less complex and thus lowers the

investment and manufacturing cost.

Formulation of gels depends on factors like

temperature modulation, pH change, presence of ions and ultra violet irradiation, from which the drug gets released in a sustained and controlled manner Various biodegradable polymers that are used for the formulation of in situ gels include gellan gum, alginic acid, xyloglucan, pectin, chitosan, poly(DL lactic acid), poly(DL-lactide-coglycolide) and poly- caprolactone.

Method of preparation of hydrogel

Several techniques have been reported for the

synthesis of hydrogels. They involves Copolymerization/crosslinking of comonomers using multifunctional co-monomer, which acts as crosslinking agent. The polymerization reaction is initiated by chemical initiator. The polymerization reaction can be carried out in bulk, in solution, or in suspension. The second method involves crosslinking of linear polymers by irradiation, or by chemical compounds . 6

The monomers used in the preparation of the ionic

polymer network contain an ionizable group, a group that can be ionized, or a group that can undergo a substitution reaction after the polymerization is completed. As a result, hydrogels synthesized contain weakly acidic groups like carboxylic acids, or a weakly basic group like substituted amines, or a strong acidic and basic group like sulfonic acids, and quaternary ammonium compounds. Some of the commonly used crosslinking agents include N, N ' methylene bisacrylamide, divinyl benzene, and ethylene glycol dimethacrylate.

1.Solution polymerization
1 Solution Polymerization/Crosslinking In

solution, co-polymerization/crosslinking reactions, and ionic or neutral monomers are mixed with the multifunctional crosslinking agent. The polymerization is initiated thermally, by UV-light, or by redox initiator system. The presence of solvent serves as heat sink, and minimizes temperature control problems. The prepared hydrogels need to be washed with distilled water to remove the unreacted monomers, crosslinking agent, and the initiator.

2. Suspension polymerization
This method is employed to prepare spherical

hydrogel microparticles with size range of 1 u.m to 1mm. In suspension polymerization, the monomer solution is dispersed in the non-solvent forming fine droplets, which are stabilized by the addition of stabilizer. The polymerization is initiated by thermal decomposition of free radicals. The prepared microparticles then washed to remove unreacted monomers, crosslinking agent, and initiator. Hydrogel microparticles of polyvinyl alcohol) and poly(hydroxy ethyl methacrylate) have been prepared by this method.

High energy radiation like gamma and electron beam, have

3. Polymerization by radiation

been used to prepare the hydrogels of unsaturated compounds. The irradiation of aqueous polymer solution results in the formation of radicals on the polymer chains. Also, radiolysis of water molecules results in the formation hydroxyl radicals, which also attack the polymer chains, resulting in the formation of macroradicals. Recombination of the macroradicals on different chains results in the formation of covalent bonds, and finally a crosslinked structure is formed . Examples of polymers crosslinked by radiation method include polyvinyl alcohol) , poly (ethylene glycol) , poly(acrylic acid) . The major advantage over chemical initiation is the production 10 of relatively pure, residue-free hydrogels.

4. Chemically crosslinked hydrogels

Polymers containing functional groups like -


OH, -COOH, -NH 2, are soluble in water. The presence of these functional groups on the polymer chain can be used to prepare hydrogels by forming covalent linkages between the polymer chains and complementary reactivity, such as aminecarboxylic acid, isocyanate-0H/NH2 or by Schiff base formation . Gluteraldehyde can be used as a crosslinking agent to prepare hydrogels of polymers containing -OH groups like polyvinyl alcohol) .

5.Physically crosslinked hydrogel

Most of the covalent crosslinking agents are

known to be toxic, even in small traces. A method to overcome this problem and to avoid a purification step, is to prepare hydrogels by reversible ionic crosslinking. Chitosan, a polycationic polymer can react with positively charged components, either ions or molecules, forming a network through ionic bridges between the polymeric chains.



Mechanisms used for triggering the in situ gel

formation of biomaterials Physiological stimuli (e.g., temperature and pH) Physical changes in biomaterials (e.g., solvent exchange and swelling) Chemical reactions (e.g. enzymatic, chemical and photo-initiated polymerization)

In situ formation based on physiological stimuli

A. Thermally trigged system

Temperature-sensitive hydrogels are

classified into Negatively thermosensitive Positively thermosensitive


Positively thermosensitive
A positive temperature sensitive hydrogel

has an upper critical solution temperature (UCST), such hydrogel contracts upon cooling below the UCST. Below this temp. solution to gel formation takes place. E.g. poly(acrylic acid) (PAA) polyacrylamide ( PAAm ) gelatin polysaccharides[carrageenan,gellan,amylose,agarose]

In the gelation mechanism of polysaccharides.

At high temperatures a random coil conformation is assumed. 2. With decreasing temperature, formation of double helices that act as knots is observed. 3. The aggregation of such helices forms the physical junctions of gels.



It can be prepared with naturally occurring

polymers. Most natural polymer aqueous solutions form a gel phase when their temperature is lowered. Classic examples of natural polymers exhibiting a solgel transition include gelatin and carrageenan. At elevated temperatures; these polymers adopt a random coil conformation in solution. Upon cooling, a continuous network is formed by partial helix formation.


Negatively thermosensitive
Negative temperature-sensitive

hydrogels have a lower critical solution temperature (LCST) and contract upon heating above the LCST. Above this temp. solution convert to gel form. E.g. methyl cellulose hydroxy propyl cellulose


1. Gradual desolvation of the polymer. 2. Increased micellar aggregation and 3. The increased entanglement of the polymeric network. Despite all the promising results obtained with thermo reversible gels, there remains an important drawback associated with their use; the risk of gelation before administration by increase in ambient temperature during packing or storage.


Methylcellulose solutions transform into

opaque gels between 40 and 50 C, whereas HPMC shows phase transition between 75 and 90C. These phase transition temperatures can be lowered by chemical or physical modifications. Eg: NaCl decreases the transition temperature of methylcellulose solutions to 3234C.


More recently, Jeong also developed novel


graft copolymers with thermo-gelling properties based on poly(ethylene glycol-g(DL-lactic acid-co-glycolic acid)) (PEG-gPLGA) and poly((DL-lactic acid-co-glycolic acid)-g-ethylene glycol) (PLGA-g-PEG). Aqueous solutions of these copolymers form soft gels at body temperature (37C) but flow freely at room temperature[25-30 C]. They are generally used for parentral purpose. Incase of implants, the duration of the PEG-gPLGA and PLGA-g-PEG gels might be tailored from 1 week to 2 months.


Phase transition temperature in aqeous solution LCST behaviour PNIPAM 3034 C 3234 C 37 C 3050 C 2085 C 2830 C UCST behaviour

poly(N,N-diethylacrylamide) Poly(methyl vinyl ether) Poly(N-vinylcaprolactam) PEO-b-PPO Poly(GVGVP)



25 C

A. Formulation & evaluation of sumatriptan

succinate nasal insitu gel using fulvic acid as novel permeation enhancer. IJPRD[octo-09] drug: sumatriptan succinate Material: fulvic acid ,pluronic PF127,carbopol974P preparation: By cold method


1. Gel strength determination A sample of 50g of the nasal gel was put in a 100 ml graduated cylinder and gelled in a thermostatically controlled water bath at 37C. A weight of 35 g was placed onto the gelled solution. The gel strength, which is an indication for the viscosity of the nasal gel at physiological temperature, was determined by the time in seconds required by the weight to penetrate 5 cm into the gel.


2. Gelation temperature: 2 ml drug soln. In test tube. Keep it in waterbath with increase in 1 C temp. Note down the temp. At which gel formed. 3. DSC study 4. Drug content 5. Mucoadhesive force 6. Viscosity determination 7. Invitro diffusion study



18% Pluronic F-127 gel formulation with 0.2%

carbopol 974P is a promising nasal drug delivery system for the antimigraine drug Sumatriptan succinate, which would enhance nasal residence time owing to increased viscosity and mucoadhesive characteristics. Finally from this study it was concluded that mucoadhesive nasal in situ gel drug delivery was very beneficial in case of BCS class III drugs like Sumatriptan succinate in presence of fulvic acid due to its permeation enhancingeffect.

Factor affecting thermo-reversible gel

A. Physicochemical properties of polymers


concentration of thermo-reversible polymer molecular weight, transition temperature hydration value polymer morphology crystal state polymorphism of polymers phase separation behavior of polymers. B. Biological factor


pH triggered systems
Depending upon the change in environment PH,

polymer may form solution to stiff gel preparation. E.g. poly ( acrylic acid) (PAA) ( Carbopol , carbomer ), cellulose acetate phthalate(CAP) latex, polymethacrilic acid(PMMA), polyethylene glycol (PEG), pseudolatexes


Polyvinylacetal diethylaminoacetate Solutions with a low viscosity at pH 4 Hydrogel at neutral pH condition

Cellulose acetate phthalate (CAP)

Solutions at pH 4.5 coagulation at pH 7.4 by the tear fluid


First preliminary investigations of pH sensitive

latexes for ophthalmic administration began in early 1980s and have been extensively studied by Boye. Cellulose acetate phthalate latex is a polymer with potentially useful properties for sustained drug delivery to the eye because latex is a free running solution at a PH of 4.4, which undergoes coagulation when the pH is raised by the tear fluid to pH 7.4. The pH change of about 2.8-3 units after instillation of the native formulation (pH 4.4) into the tear film leads to an almost instantaneous transformation of the highly fluid latex into viscous gel


The poly acrylic acid and its lightly cross-

linked commercial forms (Polycarbophil and Carbopol),also shows pH induced phase transition as the pH is raised about 5.5. The manufacturer states that Carbopol 934 gel has the lowest cross-linking density, while Carbopol 981 intermediate and Carbopol 940 have the highest, higher the cross linking & stiff gel formed.


The amount of PAA required to form stiff gel

upon instillation in the eye is not easily neutralized by the buffering action of tear fluid and as the concentration of Carbopol increases in the vehicle, its acidic nature may cause stimulation to the eye tissues. In order to reduce the total polymer content and improve the gelling properties, an ocular drug delivery system based on a combination of Carbopol and a suitable viscosity enhancing polymer Eg: HPMC or MC allows a reduction in the PAA concentration without comprising the in situ gelling properties.

The polymers with a large number of ionizable groups

are known as poly-electrolytes. All pH-sensitive polymers contain pendant acidic or basic groups that either accept or release protons in response to changes in environmental pH. . Swelling of hydrogel increases as the external pH, increases in the case of weakly acidic (anionic) groups, to form gel & viceversa. Some of examples of that are delivered by pH sensitive method include ciprofloxacin, Indomethacin, Gatifloxacin.


PH dependent approach:
A. Formulation ,evaluation & optimization of

insitu gel of ranitidine Hcl. IJPS & Nanotechnology Material: ranitidine, sodium alginate, HPMC K100, CACO3



In situ formation based on physical mechanism

A. Swelling : glycerol mono- oleate which is polar lipid that swells in water to form lyotropic liquid crystalline phase structures & finally gel. It has some Bioadhesive properties and can be degraded invivo by enzymatic action.


B. Diffusion :
This method involves the diffusion of solvent

from polymer solution into surrounding tissue and results in precipitation or solidification of polymer matrix. N-methyl pyrrolidone (NMP) has been shown to be useful solvent for such system .


In situ formation based on chemical reactions

Following chemical reaction cause gelation :

Enzymatic cross-linking,
Ionic crosslinking, Photo-initiated processes


Ionic crosslinking
K- carrageenan forms rigid, brittle


gels in presence of K + . I- carrageenan forms soft, elastic gels in presence of Ca 2+ . Gellan gum ( Gelrite ) undergoes in situ gelling in the presence of monoand divalent cations , including Ca 2+ , Mg 2+ , K + and Na + . Alginic acid undergoes gelation in presence of divalent/polyvalent cations .

gellan gum has the tendency of gelation

which is cations induced . This gelation involves the formation of double helical junction zones followed by aggregation of the double helical segments to form a threedimensional network by complexation with cations and hydrogen bonding with water . The formulation consisted of gellan solution with calcium chloride and sodium citrate complex.
In situ gelling gellan formulation as vehicle for

oral delivery of theophylline is reported.


Calcium ions in the complexed form may be included

in the formulation for the induction of pectin gelation. Sodium citrate may be added to the pectin solution to form a complex with most of calcium ions added in the formulation. By this means, the formulation may be maintained in a fluid state (sol), until the breakdown of the complex in the acidic environment of the stomach, where release of calcium ions causes gelation to occur. The quantities of calcium and citrate ions may be optimized to maintain the fluidity of the formulation before administration and resulting in gelation, when the formulation is administered in stomach.


A. Formulation & evaluation of insitu gel of

clotrimazole for oral candidiasis.


Drug :clotrimazole Polymer: gellan gum[0.1-0.75%],HPMC E15LV[0.1%], 0.17% sodium citrate, CACL2[0.05%]


Drug solution containing calcium ion in

complex form. But when come in contact with membrane fluid release calcium ion to form gelling of gelln gum. 0.05%of cacl2 & 0.17% sodium citrate considered to be best to have optimum release of calcium ion.


Enzymatic cross-linking
Cationic pH-sensitive polymers

containing immobilized insulin and glucose oxidase can swell in response to blood glucose level, releasing the entrapped insulin in a pulsatile fashion. Adjusting the amount of enzyme also provides a convenient mechanism for controlling the rate of gel formation, which allows the mixtures to be injected before gel formation

A solution of monomers or reactive macromer and initiator

can be injected into a tissue site and the application of electromagnetic radiation used to form gel . long wavelength ultraviolet and visible wavelengths are used. . Initiator:- [ a] 2,2 dimethoxy-2-pheny acetophenone in ultraviolet light systems [b] ethyleosin in visible light systems. Short wavelength ultraviolet is not used because it has limited penetration of tissue and biologically harmful


Classification of In situ polymeric systems


Pectin, xyloglucan and gellan gum


are used for in situ forming oral drug delivery systems. An orally administered in situ gelling pectin formulation for the sustained delivery of paracetamol has been reported. Main advantage of using pectin for these formulations is that it is water soluble, so organic solvents are not necessary in the formulation

In situ gelling gellan formulation as vehicle

for oral delivery of theophylline is reported. The formulation consisted of gellan solution with calcium chloride and sodium citrate complex. When administered orally, the calcium ions are released in acidic environment of stomach leading to gelation of gellan thus forming a gel in situ


Ocular- delivery
Polymer used :-

Gellan gum, alginic acid and xyloglucan Drug used for Ocular in situ drug delivery:Antimicrobial agents, anti inflammatory agents and autonomic drugs used to relieve intraocular tension in glaucoma

Conventional delivery systems often

result in poor bioavailability and therapeutic response because high tear fluids turn over and dynamics cause rapid elimination of the drug from the eye . So, to overcome bioavailability problems, ophthalmic in situ gels were developed. Drug release from these in situ gels is prolonged due to longer pre-corneal contact times of the viscous gels compared with conventional eye drops.

Nasal -drug delivery system:

In-situ gel was found to inhibit the increase in

nasal symptoms in treatment of allergic rhinitis as compared to marketed formulation. for nasal delivery of insulin- The formulation was in solution form at room temperature that transformed to a gel form when kept at 37 C. Nasal in situ drug delivery system is suitable for protein and peptide drug delivery & brain targetted disease through nasal route.


Rectal and vaginal delivery:

xyloglucan based thermo reversible gels used

for rectal drug delivery of indomethacin.

prolonged release vaginal gel incorporating

clotrimazole - - cyclodextrin complex was formulated for the treatment of vaginitis

They observe that in situ gel has broad drug


absorption peak and a longer drug residence time as compared to commercial preparation.

Injectable-Drug Delivery Systems:

A novel, injectable, thermosensitive in

situ gelling hydrogel was developed for tumor treatment. This hydrogel consisted of drug loaded chitosan solution neutralized with glycerophosphate


Polymers used in insitu gels

A polymer used to prepare in situ gels should

have following charterstics: 1. It should be biocompatible. 2. It should be capable of adherence to mucus. 3. It should have pseudoplastic behaviour. 4. It should have good tolerance and optical clarity. 5. . It should influence the tear behaviour.


Pectins are a family of polysaccharides, in which the

polymer backbone mainly comprises -(1-4)-Dgalacturonicacid residues.


methoxypectins readily form gels in aqueous

solution in the presence of free calcium ions, which crosslink the galacturonic acid chains. Although the gelation of pectin will occur in the presence of H + ions, a source of divalent ions, generally calcium ions is required to produce the gels that are suitable as vehicles for drug delivery.

The main advantage of using pectin for these formulations is that it is water soluble, so organic solvents are not necessary in the formulation. Divalent cations present in the stomach, carry out the transition of pectin to gel state when it is administered orally. Calcium ions in the complexed form may be included in the formulation for the induction of pectin gelation.


Sodium citrate may be added to the pectin solution to form a complex with most of calcium ions added in the formulation. By this means, the formulation may be maintained in a fluid state (sol), until the breakdown of the complex in the acidic environment of the stomach, where release of calcium ions causes gelation to occur. The quantities of calcium and citrate ions may be optimized to maintain the fluidity of the formulation before administration and resulting in gelation, when the formulation is administered in stomach. The potential of an orally administered in situ gelling pectin formulation for the sustained delivery of Paracetamol has been reported. 63

Xyloglucan is a polysaccharide derived from

tamarind seeds and is composed of a (1-4)--Dglucan backbone chain, which has (1-6)--D xylose branches that are partially substituted by (1-2)--Dgalactoxylose. When xyloglucan is partially degraded by galactosidase, the resultant product exhibits thermally reversible gelation by the lateral stacking of the rod like chains. The sol-gel transition temperature varies with the degree of galactose elimination.

It forms thermally reversible gels on warming

to body temperature. Its potential application in oral delivery exploits the proposed slow gelation time (several minutes) that would allow in-situ gelation in the stomach following the oral administration of chilled xyloglucan solution. Xyloglucan gels have potentially been used for oral, intraperitoneal, ocular and rectal drug delivery.

Gellan gum (commercially available as Gelrite


TM or Kelcogel TM ) is an anionic deacetylated exo-cellular polysaccharide secreted by Pseudomonas elodea with tetrasaccharide repeating unit of one -Lrhamnose, one -D-glucuronic acid and two -D-glucuronic acid residues. Chemical structure of the polysaccharide has a tetrasaccharide repeat unit consisting of two glucose (Glc) residues, one glucuronic acid (GlcA) residue, and one rhamnose (Rha) residue. These are linked together to give a tetrasaccharide repeat unit.

It has the tendency of gelation which is

temperature dependent or cations induced . This gelation involves the formation of double helical junction zones followed by aggregation of the double helical segments to form a threedimensional network by complexation with cations and hydrogen bonding with water . The formulation consisted of gellan solution with calcium chloride and sodium citrate complex.
In situ gelling gellan formulation as vehicle for

oral delivery of theophylline is reported.

Effect of Mg2 and Ca2 on gel hardness has been shown in following graph.


Alginic acid is a linear block copolymer

polysaccharide consisting of -D-mannuronic acid and -L-glucuronic acid residues joined by 1,4glycosidic linkages . The proportion of each block and the arrangement of blocks along the molecule vary depending on the algal source. Dilute aqueous solutions of alginates form firm gels on addition of di and trivalent metal ions by a crosslinking process involving consecutive glucuronic residues in the -Lglucuronic acid blocks of the alginate chain.

Alginic acid can be chosen as a vehicle for

ophthalmic formulations, since it exhibits favorable biological properties such as biodegradability and non toxicity. A prolonged pre-corneal residence of formulations containing alginic acid was looked for, not only based on its ability to gel in the eye, but also because of its mucoadhesive properties.


Xanthan gum
Xanthan gum is a high molecular weight extra cellular

polysaccharide produced by the fermentation of the gramnegative bacterium Xanthomonas campestris. The primary structure of this naturally produced cellulose derivative contains a cellulosic backbone (-D-glucose residues) and a trisaccharide side chain of -D-mannose-D-glucuronicacid--D-mannose attached with alternate glucose residues of the main chain. The anionic character of this polymer is due to the presence of both glucuronic acid and pyruvic acid groups in the side chain.


Chitosan is a biodegradable, thermosensitive, polycationic

polymer obtained by alkaline deacetylation of chitin, a natural component of shrimp and crab shell. Chitosan is a biocompatible PH dependent cationic polymer, which remains dissolved in aqueous solutions up to a pH of 6.2. Neutralization of chitosan aqueous solution to a pH exceeding 6.2 leads to the formation of a hydrated gel like precipitate. It forms gel without any chemical modification or cross linking by addition of polyol salts bearing a single anionic head such as glycerol, sorbitol, fructose or glucose phosphate salts to chitosan aqueous solution.

Carbopol is a well known pH dependent polymer,

which stays in solution form at acidic pH but forms a low viscosity gel at alkaline pH.
HPMC is used in combination with carbopol to impart

the viscosity to carbopol solution, while reducing the acidity of the solution.
Based on this concept, the formulation and evaluation

of an ophthalmic delivery system for indomethacin for the treatment of uveitis was carried out.

Poloxamers or pluronic (marketed by BASF

Corporation) are the series of commercially available di functional tri block copolymers of non-ionic nature. They comprise of a central block of relatively hydrophobic polypropylene oxide surrounded on both sides by the blocks of relatively hydrophilic poly ethylene oxide. Due to the PEO/PPO ration of 2:1, when these molecules are immersed into the aqueous solvents, they form micellar structures above critical micellar concentration. They are regarded as PEO-PPO-PEO copolymers.

Chemically they are Oxirane, methyl-, polymer with oxirane

or -Hydro-- hydroxypoly(oxyethylene),a poly(oxypropylene), poly(oxyethylene) a block copolymer. The pluronic triblock copolymers are available in various grades differing in molecular weights and physical forms. Depending upon the physical designation for the grades are assigned, as F for flakes, P for paste, L for liquid. They are triblock copolymers consisting of poly(oxyethylene) and poly(oxypropylene) units that undergo changes in solubility with change in environment temperature. Pluronics or Poloxamers also undergo in situ gelation by temperature change.


Pluronic F 127 a 25-40% aqueous solution of this

material will gel at about body temperature, and drug release from such a gel occurs over a period of up to one week.
Pluronic F-127 was used as an in situ gel forming

polymer together with mucoadhesive polymers such as Carbopol 934 and hydroxylpropyl methylcellulose to ensure long residence time at the application site.
Controlled release of drug was achieved in-vitro

indicating antimycotic efficacy of developed formulation for a longer period of time.


Novel Synthetic polymers are popular choice mainly

for parenteral preparations.

The trend in drug delivery technology has been

towards biodegradable polymers, requiring no follow up surgical removal, once the drug supply is depleted.
Aliphatic polyesters such as poly (lactic acid), poly

(glycolic acid), poly (lactide- coglycolide), poly (decalactone), poly -caprolactone have been the subject of the most extensive recent investigations.

Jeong and co-workers described different

thermosensitive, biodegradable hydrogels based on poly(lactic acid). Block copolymer solutions of PEO and poly(Llactic acid) were shown to be in the sol state at 45 C, and in the gel state at body temperature . Demerit: However, the need to heat the solution limits the nature of the drugs that can be incorporated in this delivery system, and makes the injection procedure not practical.

Later, PEO-b-(D,L-lactic acid-co-glycolic acid)-b-PEO (PEOPLGA-PEO) triblock copolymer solutions were found to form, at room temperature, a free-flowing sol that became a transparent gel at 37 C. PEO-PLGA-PEO exhibited a critical gel concentration of approximately 16 wt%. PEO-PLGA-PEO polymers are amphiphilic and yield micelles in aqueous environments with the hydrophilic PEO occupying the outer shell region, and the hydrophobic constituting the inner core


It was shown that the gels formed via a

micellar aggregation mechanism. above 30 C, sudden increase in polymer polymer attraction . Other studies established that micelle micelle clusters were formed through hydrophobic interactions between core phases. Micelle formation was indeed confirmed by 13C-NMR and dye solubilization studies.

The more hydrophobic the polymer, the lower


the temperature and polymer concentration required to achieve the desired liquid crystalline structure . As opposed to poloxamers, PEO-PLGA-PEO gels do not erode rapidly & based on miscelle formation. Furthermore, due to their PLGA segments, they can be hydrolyzed in vivo. Demerit:- Since the transition temperature of the triblock copolymers is quite sensitive to PEO length, it is difficult to modify polymer structure and still maintain gelation temperature around 37 C.

To overcome the molecular weight limitation


developed graft copolymers based on PEO and PLGA. As with the PEO-PLGA-PEO system, PEO-gPLGA and PLGA-g-PEO micellized in water . The critical gel concentration of both polymers were 22 wt%. In vivo, the PLGA-g-PEO depot persisted for about 3 months, whereas PEO-g-PLGA disappeared within a week. By mixing two polymers of PEO-g-PLGA and PLGA-g-PEO, the duration of depot could be adjusted between 1 week and 3 months.

Low molecular weight PLGA-PEO-PLGA

copolymers also exhibit reverse thermal gelation properties at concentrations between 10 and 30 wt% .
In vitro release experiments showed

sustained paclitaxel release over 50 days. This was in sharp contrast to the complete release of paclitaxel from poloxamer 407 hydrogel within 1 day.


Timoptic -XE

It is a timolol maleate ophthalmic gel

formulation. Dosage strengths 0.25% and 0.5% in market . (Each ml of Timoptic -XE 0.25% contains 2.5 mg of timolol (3.4 mg of timolol maleate ). pH of solution is approximately 7.0 Inactive ingredients include gellan gum, tromethamine , mannitol , and water for injection and the preservative used is benzododecinium bromide 0.012%.

Regel is one of the Macromed's proprietary

drug delivery system and based on triblock copolymer, composed of poly ( lactide -coglycolide ), poly (ethylene glycol), poly( lactide co- glycolide ). It is a thermally reversible gelling polymers developed for parenteral delivery that offers a range of gelation temperature, degradation rates and release characteristics as a function of molecular weight, degree of hydrophobicity and polymer concentration.

Oncogel is a frozen formulation of paclitaxel in

Regel. It is a free flowing liquid below room temperature which upon injection forms a gel in-situ in response to body temperature. hGHD-1 is a novel injectable depot formulation of human growth hormone (hGH) utilizing Macromed's Regel drug delivery system for treatment of patients with hGHdeficiency



1) Viscosity and rheology Measured using Brookfield rheometer or some

other type of viscometers such as Ostwald's viscometer. The viscosity of these formulations should be such that no difficulties are arised during their administration by the patient, especially during parenteral and ocular administration 2) Clarity The clarity of formulated solutions determined by visual inspection under black and white 87 background.

3) Texture analysis Firmness, consistency and

cohesiveness of formulation are assessed using texture analyzer which mainly indicates the syringeability of sol so the formulation can be easily administered in-vivo. Higher values of adhesiveness of gels are needed to maintain an intimate contact with surfaces like tissues

4) Determination of mucoadhesive Force:

Mucoadhesive force was the minimum weight

required to detach two vials.


5) Gel Sol-Gel transition temperature

& gelling time

sol-gel transition temperature may be

defined as that temperature at which the phase transition from sol meniscus to gel meniscus is occurred. Gel formation is indicated by a lack of movement of meniscus on tilting the tube Gelling time is the time for first detection of gelation.

6) Gel-Strength
This parameter can be evaluated using

a rheometer . Method: The changes in the load on the probe can be measured as a function of depth of immersion of the probe below the gel surface.


7) Thermogravimetric analysis

can be conducted for in situ forming

polymeric systems to quantitate the percentage of water in hydrogel. Differential scanning calorimetry is used to observe if there are any changes in thermograms as compared with the pure ingredients used thus indicating the interactions .


8) In-vitro drug release studies

The drug release studies are carried out by

using the plastic dialysis cell which is made up of two half cells, donor compartment and a receptor compartment . Both half cells are separated with the help of cellulose membrane. Sol form of formulation is placed in donor compartment. The assembled cell is then shaken horizontally in an incubator. The total volume of the receptor solution can be removed at intervals and replaced with the fresh media.



Polymer used

Route of administration



Gellan gum


Four five fold increase of bioavailability in rats and three fold in rabbits as compared to comercial oral formulation Sustained delivery of anti cancer drug for a long period app. 100 hr.


Human serum albumin and tartric acid derivative


Paracetamol and Ambroxol Metoclopramide hydrochloride



Sustained oral delivery

Poloxamer 407 and polyethylene glycol


Ease of administration, accuracy of dosing, prolonged nasal residence and improved drug bioavailability Formulation having sustained drug action for 12 hours.

Cinnarizine 94

4% of sodium alginate with 0.5% of calcium carbonate


Drug Sumatriptan

Polymer used Pluronic F127 (PF127) and Carbopol 934P Carbopol and Chitosan

Route of administration Nasal

Results prolonging nasal residence time and increase nasal absorption Therapeutically efficacious and showed a diffusion controlled type of release behaviour over 24 h periods.

Timolol Maleate


clarithromycin and metronidazole benzoate

Itraconazole (1%w/w). Salbutamol Sulphate

Sodium alginate and CaCO 3


Sustained oral delivery

Polaxamer with carbopol 934 carbopol 934 and HPMC

oral topical gels ( mucoadhesive buccal gel) nasal

increase in Buccal residence time and patient comfort sustained release and higher bioavailability