In-situ Ophthalmic Gel Ppt

1Kamal Singh Rathore*, 2Nema R.K., *1BN Girls College of Pharmacy, UdaipurRaj.313002 2Rishiraj College of Pharmacy, Indore-M.P. [email protected] +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 METABOLISM

PRECORNEAL AREA

CORNEAL ABSORPTION CONJUNCTIVAL ABSORPTION

DRINAGE

INDUCED LACRIMATION

NORMAL TEAR 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 culde-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) Gellan Gum (Balasubramaniam Et Al., 2003)  Indomethacine In-situ Gelling System (Sultana et al., 2006a)  Pefloxacin mesylate In-situ Gelling System Gellan Gum In-situ Gelling System Alginate (Cohen Et Al., 1997)  Pilocarpine In-situ Gelling System Alginate (Demailly Et Al., 2001)  Carteolol In-situ Gelling System Alginate/HPMC (Liu Et Al., 2006)  Gatifloxacin In-situ Gelling System Carbopol® 940/HPMC (Srividya Et Al., 2001)  Ofloxacin Poloxamer/Hyaluronic Acid (Cho Et Al., 2003)  Ciprofloxacin In-situ Gelling System In-situ Gelling System Pluronic F127, MC, HPMC (Desai & Blanchard, 1998)  Pilocarpine In-situ Gelling System Pluronic F127/Carbopol (Lin & Sung, 2000)  Pilocarpine Pluronic F127, Xyloglucan (Miyazaki Et Al., 2001)  Pilocarpine In-situ Gelling System in-situ gelling system Pluronic F127, CMC, HPMC (El-Kamel, 2002)  Timolol

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 sustainedrelease 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

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