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A Review On Topical Ophthalmic Drug Delivery Systems

1K.S.Rathore*, 2R.K.Nema, 3S.S.Sisodia, 3M.S.Ranawat

1B. N. Girls College of Pharmacy, Udaipur

2Rishiraj College of Pharmacy, Indore

3B.N. College of Pharmacy, Udaipur

Eye is unique and very precious organ. It is considered as window of the soul. We can enjoy and viewed the whole world only with this organ. There are many eye ailments which affect this organ and one can loss the eye sight also. Therefore many ophthalmic drug delivery systems are available. These are classified as conventional and newer drug delivery systems.Most commonly available ophthalmic preparations are eye drops and ointments. But these preparations when in­stilled into the cul-de-sac are rapidly drained away from the ocular cavity due to tear flow and lacrimal nasal drainage. Only a small amount is available for its therapeutic effect resulting in frequent dosing1. Thus inefficient drug delivery into the eye occurs due to rapid tear turn over, lacrimal. drainage and drug dilution by tears2.

Topical administration for ocular therapeutics is ideal because of smaller doses required compared to the sys­temic use, its rapid onset of action and freedom from sys­temic toxicity Topically applied ocular drugs have to reach the inner parts of the eye and transcorneal penetration is believed to be the major route for drug absorption. Corneal absorption is much slower process than elimination. For many drugs K loss (First order elimination rate) is approxi­mately 0.5-0.7/min and K absorption (First order absorp­tion rate) is about 0.001/min. The sum of these two rate constants control the fraction of the applied dose absorbed into the eye3. So the ocular bioavailability can be increased by decreasing K Ioss or by increasing K absorption. The former can be achieved by modifying the ocular dosage forms and the latter by formulating ocular dosage forms containing lipophilic prodrugs or by adding penetration enhancers. Therefore to optimize topical ocular drug deliv­ery system prolonged contact time with the corneal surface and better penetration through cornea is necessary4.

A considerable amount of effort has been made in ophthalmic drug delivery since 1970's. The two main ap­proqches attempted are improvement in bioavailability and controlled release drug delivery.

ENHANCEMENT IN BIOAVAILABILITY

            Topical bioavailability can be improved by maximizing precorneal drug absorption and minimizing precorneal drug loss.

1.  Viscosity improver:

In order to prolong precorneal residence time and to improve bioavailability attempts were made to increase the viscosity of the formulation. The viscosity enhancers used were hydrophilic polymers such as cellulose, polyalcohol and polyacrylic acid. Sodium carboxy methyl cellulose is one of the most important mucoadhesion polymers having mono adhosive strength5. The effects of polyacrylic acid and polyacrylamide based hydrogels are tested on miotic
re­sponse of pilocarpine. Carbomer were used in liquid and semisolid formulations as suspending or viscosity increas­ing agents. Formulations including creams, gels and oint­ments were used as ophthalmic products6. Polycarbophil is water insoluble cross linked polyacrylic acid helps in the retention of the drug delivery system in the eye7 due to the formation of hydrogel bonds and mucoadhesive strength. Hyaluronic acid offers a biocompatible and biodegradable matrix for fabrication of ocular sustained release dosage form- Dosage forms based on the benzyl esters of hyalu­ronic acid were used for ophthalmic sustained release of methyl prednisolone. Films and microspheres were also prepared from hyaluronic acid. Polysaccharide such as xanthan gum was found to increase the viscosity8. Today, hydrophilic polymers continue to be used in formulation of ophthatmic products Outs the" lunotions are mere for patient comfort and for bioadhesion rather than viscosity en­hancement. Viscosity vehicles increases the contact time and no marked sustaining effect is seen.

2.    Gels :

      Gel formation is an extreme case of viscosity enhance­ment through the use of viscosity enhancers. So the dosing frequency can be decreased to once a day9. Cellulose ac­etate phthalate dispersion constituted a micro-reservoir system of high viscosity. Poloxamer 407 is used as an oph­thalmic vehicle for pilocarpine delivery and found that the gel formation enhances the activity of pilocarpine10. Timolol maleate form thermogelling drug delivery system composed of cellulose ether ethylhydroxylethylcellulose11. The effect of flurbiprofen a non steroidal anti inflammatory, formulated in carbopol 940 and pluronic F 127 hydrogels were com­pared in ocular hypertension. Gelrite is a polysaccharide (gellen gum), which forms a clear gel in the presence of mono or divalent cation. The high viscosity of the gel, how­ever, results in blurring of vision and malted eyelids which substantially reduce patient acceptability. Sterilization is another drawback for large-scale production,

3.    Penetration enhancers:

      They act by increasing corneal uptake by modifying the integrity of comeal epithelium. Chelating agents, pre­servatives, surfactants and bile salts were studied as pos­sible penetration enhances. But the effort was diminished due to the local toxicity associated with enhancers12. Pen­etration enhancers have also been reported to reduce the drop size of conventional ophthalmic solutions especially if they do not elicit local irritation.

4.    Prodrugs:

      Prodrugs enhance comeal drug permeability through modification of the hydrophilic or lipophilicity of the drug13. The method includes modification of chemical structure of the drug molecule, thus making it selective, site specific and a safe ocular drug delivery system. Drugs with increased penetrability through prodrug formulations are-epinehrine13, phenylephrine, timolol, pilocarpine14 and albuterol.

5.    Cyclodextrins:

      Cyclodextrins act as carriers by keeping the hydropho­bic drug molecules in solution and delivering them to the surface of the biological membrane, where the relatively lipophilic membrane has a much lower affinity for the hy­drophilic eyclodextrin molecules WO therefore they remain in the aqueous vehicle system. Optimum bioavailability can be achieved when just enough cyclodextrin (

6.    Bioadhesive polymers:

      The bioadhesive polymers16 adhere to the mucin coat covering the conjunctiva and the comeal surfaces of the eye, thus prolonging the residence time of a drug in the conjunctival sac. These polymers can be neutral, synthetic or semi synthetic. Polyacrylic acid, polycarbophil and hy­aluronic acid are synthetic polymers commonly used. Chitosan is a bioadhesive vehicle suitable for ophthalmic formulation since it exhibits general biological properties such as biodegradability, nontoxicity and biocompatibility. Due its positive charge at neutral pH and ionic interaction with the negative charges of sialic acid occurs. Xanthan and carrageenan are also described as bioadhesive polysaccharides17.

ENHANCEMENT  IN CONTROLLED DRUG-DELIVERY

      It is realized that the preferred system of ophthalmic delivery would provide improved bioavailability, site-spe­cific delivery and with continuous drug release. So achieve­ments have been made in the following areas:

1.    In situ forming gels:

      The progress has been made in gel technology lip the development of droppiable gel. They are liquid uponjnstil­lation and undergo phase transition in the ocular cul-de-sac to form visco-elastic gel and this provides a response to environmental changes18. Three methods have been employed to cause phase transition in the eye surface. These are change in pH, change in temperature and ion activa­tion.

1.  pH:

      In this method gelling of the solution is triggered by a change in the pH. CAP latex cross linked polyacrylic acid and derivatives such as carbomers are used. They are low viscosity polymeric dispersion in water which undergoes spontaneous coagulation and gelation after instillafion in the conjunctival cul-de-sac19.

3.    Temperature:

      In this method gelling of the solution is triggered by change in the temperature. Sustained drug delivery can be achieved by the use of a polymer that changes from solu­tion to gel at the temperature of the eye. But disadvantage of this is characterized by high polymer concentration (25% Poloxamers) 20. Methyl cellulose and smart hydrogels are other examples.

4.    Ionic strength:

      In this method gelling of the solution Instilled Is trig­gered by change In the Ionic strength. Example Is Gelrite. Gelrite is a polysaccharide, low acetyl gellan gum, which forms a clear gel in the presence of mono or divalent cat­ions. The concentration of sodium in human tears is 2.6 g/l is particularly suitable to cause gelation of the material when topically installed into the conjunctival sac.

5.    Oil in water emulsions:

      Phospholipids and pluronics were used as the emulsi­fiers. Antioxidants were added to improve their shelf-life. The intra-ocular pressure reducing effect of a single, topi­cally administered dose of a pilocarpine emulsion lasted for 29 h in rabbits compared to generic pilocarpine solution which lasted only for 5 h21. Oil in water emulsion is useful for delivery of Water insoluble drugs, which is solubilised in the internal oil phase.

6.    Colloidal part Iles:

      The potential use of polymeric colloidal particles as ophthalmic drug delivery systems started in late 1970's.The first two systems studied in this area were pilocarpine cellulose acetate hydrogen phthalate latex systems and piloplex. But both the system could not enter commercial development because of various issues, like local toxicity, non-biodegradable polymer and large scale sterilization.

7.    Liposomes :

      The use of liposomes as a topically administered ocu­lar drug delivery system began in the early stage of re­search into ophthalmic drug delivery. But the results were favorable for lipophilic drugs and not for-hydrophilic drugs. It was concluded that liposomes must be suitable for ocular drug delivery, provided, they had an affinity for, and were able to bind to, ocular surfaces, and release contents at optimal rates22. Positively charged liposomes have a greater affinity, to increase both precorneal drug retention and drug bioavailability .The addition of stearylamine to a liposomal preparation enhanced the corneal absorption of dexamethyl valerate. The corneal epithelium is thinly coated with nega­tively charged mucin to which the positive surface charge of the liposome may absorb more strongly. Coating with bioadhesive polymers to liposomes, prolong the precomea retention of liposomes. Carbopol 1342-coated pilocarpine23 containing liposomes were shown to produce a longer du­ration of action. Liposomal preparation of acetazolamide24, hydrocorti­sone25 and tropicamide26 has been reported. Coating the lipueme with bioadhesive polymat Ilka carbopal increased the corneal retention followed by sustained action Cyclosporin applied topically to the eye in the olive oil crops in a liposome encapsulated form and in a cellophane shield showed slow releasing property.

8.    Nanoparticles:

      Nanoparticles provide sustained release-and pro­longed therapeutic activity when retained in the cul-de-sac after topical administration and the entrapped drug must be released from the particles at an appropriate rate. To enhance particle retention, it is desirable to fabricate the particles with bioadhesive materials. Biodegradation is also a highly desirable property for the fabrication of nanoparticles. Most commonly used polymers are venous poly (alkyl cyanoacrylates), poly S-caprolactone and polylactic-co-glycolic acid, which undergo hydrolysis in tears. Coating of nanoparticles with bioadhesive polymers improves the bioavailability. Chitosan coated nanocapsules improve the bioavailability27. Nanoparticles as an oph­thalmic drug delivery have been demonstrated for both hydrophilic and hydrophobic drugs28-29.

9.    Miarcipartlauldles:

      They are drug containing, micron sized polymeric par­ticles suspended in a liquid medium. Drugs can be physi­cally dispersed in the polymer backbone30. The drug is re­leased in cul-de-sac through diffusion, chemical reaction, and polymer degradation and micro particles are larger than nanoparticles. Acyclovir loaded chitosan microspheres31 and Pilocarpine-loaded albumin or gelatin microspheres32 are available. Microparticulate technology has the advantage of better patient acceptability, since they can be topically administered as an eye drop33. But the manufacture and control of large scale manufacturing of sterile micro particulates is very challenging and expensive.

10. Inserts:

      Solid inserts were introduced into the market 50 years ago. The first solid insert was described in 1948 in British Pharmacopoeia. It was an atropine containing gelatin wa­fer and in 1980's numerous systems were developed using various polymora and different drug release principles for controlled drug release.

      Insoluble inserts are polymeric systems into which the drug is incorporated as a solution or dispersion21. Oph­thalmic inserts (ocuserts) have been reported using algi­nate salts, PVP, modified collagen and HPC, Ocufit is a silicone elastomer based matrix that allows for the con­trolled release of an active ingredient over, a period of at least 2 weeks22. Osmotically controlled inserts  have also been described, where release is by diffusion and osmoti­cally controlled4.

      Soluble inserts consists of all monolytic polymeric de­vices that at the end of their release, the device dissolve or erode. Soluble ophthalmic drug inserts is a soluble copoly­mer of acrylarnide, N-vinyl pyrrolidone and ethyl acrylate. It is a sterile thin film or wafer of oval shape. The system soften in 10-15 sec after introduction in to the upper conjuctivall sac, gradually dissolves within 1 h, while releasing the drug. A soluble insert containing gentamycin sulphate and dex­amethasone phosphate has been developed Pilocarpine Insert for glaucoma is also reported. But these systems have the drawback that that blur vision while the polymer is dissolving. Water soluble bioadhesive component in its formulation has been developed to decrease the risk of expulsion and ensure prolonged residence in the eye, com­bined with controlled drug release. They are bioadhesive ophthalmic drug inserts. A system based on gentamycin obtained by extrusion of a mixture of polymers, showing a release timer of about 72 h has been reported. Due to difficulty with self-insertion, foreign body sensation, only few insert products are listed and pharmaceutical manu­facturers are not actively developing inserts for commer­cialization.

11. Implantable systems:

      The poly lactic acid and its copolymers with glycolic acid have been used extensively as implants. An ocular implant for delivering ganciclovir for the treatment of cy­tomegalovirus has also been developed24. This delivers drug directly to the retina for over 5 months. These systems are less popular as they require minor surgery.

12. Minidisc:

      Minidisc is a controlled release monolithic matrix type device consisting of a contoured disc with a convex front and a concave back surface26. The principle component is A (1) bis (4-methacryloxybutyl)-polydimethyI siloxane. They can be made hydrophilic and hydrophobic to permit ex­tended release of bath water soluble and water insoluble drugs.

13. Soft contact lenses:

      The most widely used Material is poly-2-hydrosyethylmethacrylate. Its copolymers with PVP are used both to correct eyesight and hold and deliver drugs. Con­trolled release can be obtained by binding the active ingre­dient via biodegradable covalent linkages31.

14. Niosomes:

      Niosomes are reported as successful ophthalmic carriers. Discoidal niosomes dscomes of timolol maleate have been reported to be promising systems for the con­trolled ocular administration of water soluble drugs20. The disc shape provides for a better fit in the cul-de-sac of the eye and then large size may prevent release their drainage into the systemic pool.

15. Pharmacosomes:

      They are the vesicles formed by the amphiphilic drugs. Any drug possessing a free carboxyl group or an active hydrogen atom (-OH, -NH2) can be esterifies to the hydroxyl group of a lipid molecule, thus generating an amphiphilic prodrug. These are converted to pharmacosomes on dilution with water. They show greater stability, facilitated transport across the cornea and a con­trolled release profile16.

16. Collagen shields:

      They are manufactured from porcine scleral tissue, which bears a collagen composition similar to that of hu­man cornea. They are hydrated before being placed on the eye and the drug is loaded with the collagen shield simply by soaking it in the drug solution. They provide a layer of collagen solution that lubricates the eye. Collagen shields presoaked in tobramycin were used to treat Pseudomonas aeruginosa infected cornea excoriation28. But shield are not fully transparent and thus reduce visual activity. But they are appropriate delivery systems for both hydrophilic and hydrophobic drugs with poor penetration properties.

RECENT ADVANCES

      New ophthalmic delivery system includes ocular in­serts, collagen shields, ocular films, disposable contact lens and other Novel drug delivery systems like hiosomes20 and nanoparticles29. Newer trend is a combination of drug de­livery technologies for improving the therapeutic response of a non efficacious drug. This can give a superior dosage forms for topical ophthalmic application.

SUMMARY

      Among these drug delivery systems, only few products have been, commercialized. An ideal system should have effective drug concentration at the target tissue for a tended period of time with minimum systemic effect. Patient acceptance is very important for the design of any comfort­able ophthalmic drug delivery system. Major Improvements are required in each system like improvement in sustained drug release, large scale manufacturing and stability. Com­bination of drug delivery systems could open a new direc­tive for improving the therapeutic response of a non-effica­cious system. They can overcome the limitations and com­bine the advantages of different systems.

REFERENCES

1.  Aggarwal, D. and Kaur, I.P. Int. J. Pharm., 2005, 290, 155.

2.  Bharath, C. and Hiremath. S-R., Pharmazie, 1999, 51, 55.

3.  Calvo, P., Vila-Jato, L. and Alanso, M.J.. Int. J. Pharm., 1997 153, 41.

4.  Daragour, S., U.S Patent No. 147, 647, 1992.

5.  Davios, Davies Clin, Exp, Pharmasol. Physiol., 90W. 27, 558,

6.  Deshpande S.G. and Shirolkar, S., J. Pharm. Pharmacol., 1989, 41,197.

7.  Durrani, A.M., Farr, S.J. and Kellaway. I.W.. J. Pharm. Pharmacol., 1995, 47, 581.

8.  Gazayerly, E.L., Omaima. N. and Hikal. A H . Int. J. Pharm. 1997. 158,121.

9.  Hui. H.W. and Robinson, J.R., Int. J. Pharm., 1985. 26, 203.

10.  Kamal S.Rathore, Dr. R.K.Nema, "Glaucoma: a review" published on-line at www.earticlesonline.com (Jan4, 2009).

11.  Kaur, I.P. and Smitha. R., Drug Develop. Ind. Pharm., 2002 28. 353.

12.   Keistea, J.C., Cooper, E.R., Missel, P.J., Long, J.C. and Hager, D.F. J. Pharm. Sci, 1991, 80, 50.

13.  Khopade, A.J. and Jain, N.K., Pharmazie, 19%. 50, 812.

14.   Kumar, S., Haglund, B.O. and Himmelstein, K.J., J. Ocul. Pharmcol., 1994,10,47.

15.   Kurz, D. and Ciullla, T.A., Ophthalmic Clin. North. Amer.. 2002,15.405.

16.  Latorre F. and Nicolal, A.P., Drugs Exp, Clin, Res.. 1998, 24, 153.

17.  Lee, V.H.L. and Robinson, J.R., J. Ocul. Pharmacol., 1986, 2, 67.

18.   Lin. H.R. and Sung. K.C., J. Contol. release, 2000, 69, 379.

19.   lnduPal. K. and Meenakshi, K., Drug Develop. Ind. Pharm., 2002, 473.

20.  Marshall. W.S. and Klyee, S.D., J. Membrane Biol., 1983, 73, 275.

21.  Meseuger, G., Gumy, R., Buri, P., Rozier, A. and Plazonnet, B., Int. J. Pharm., 1993, 95, 229.

22.  Middleton, D.L, Leung, S.H.S. and Robinson, J.R., In; Lenaerts,V and Gummy, R., Eds., Bioadhesive Drug Delivery Systems, CRC Press, Boca Raton., 1990. 203.

23.  Monem, A.S, Ali, FM. and Ismail. M W . Int. J. Pherm., 2000 198, 20.

24.  Nagarsenker, M.S., Londhe, VY. and Nadkarni. G D. Int. J. Pharm., 1999, 190, 63.

25.  Rathore K.S., Nema R.K., "Management of Glaucoma: a review" International Journal of Pharm Tech Research, Vol.1, No.3, pp, July-Sept. 2009.

26.   Rathore K.S., nema R.K., "An Insight into Ophthalmic Drug Delivery System", published online at www.ijpsdr.com. June-Aug.2009 issue

27.  Rathore K.S., Nema R.K., "Review on Ocular inserts" International Journal of Pharm tech Research, Vol.1, No.2, pp 164-169, April-June 2009.

28.  Rathore K.S., Nema R.K., "Formulation and evaluation of ophthalmic films for timolol maleate" planta indica, vol.no.4, October-December, 2008, p49-50.

29.  Simamora, P., Nadkarni, S.R., Lee, Y.C. and Yalkowsky, S.H., Int. J. Pharm., 1998, 170, 209.

30.  Urtti, A., RouhWnen, H., Kaila, T. and Saano. V., Pharm. Res., 1994.11,1278.

31.  Wei, G., Xu, H., Ding, PT, U. S.M. and Zheng. J.M., J. Control. Release, 2002, 83, 65.

32.   Yasmin. S. and Asgar. A.. Pharma Times, 1998. 13.

33.  Zimmer, A.K., Chetoni, R. Saettone, M.P. Zerbe, H. and Kreuter, J., J. Control. Release, 1995. 33, 31.

 

About the Author

Kamal Singh Rathore, reader, BN Girls College of Pharmacy, Udaipur *E-mail: kamalsrathore@yahoo.com;kamalsrathore@gmail.com Mobile: +919828325713

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Hot Wheels Delivery Vehicles Wave 10 Case $47.99 Special delivery into your collection! Classic rides of the past! Great for Hot Wheels collectors! This 996N case contains the following, 12 assorted die-cast vehicles (subject to change): 1x Volkswagen Deluxe Station Wagon 1x 8 Crate 2x 1949 Ford C.O.E. 2x 1969 Custom Volkswagen Variant 1x Double Demon Delivery 1x Ice Cream Truck 1x 1972 Ford Ranchero 1x 1929 Ford Pickup 2x 1977 Custom Dodge Van Collectors asked. Hot Wheels responded. These castings of our most popular delivery cars are sure to be a fan favorite. Choose from 34 cars in 1:64 scale with real-world auto parts branding and opening features. Fill your "garage" with all of them! Not for use with some Hot Wheels sets.

(Pack of 4) 4330-08 - Liquid Scale Dissolver, 4330-08 Scale Dislv 1Gal, Liq Scale Disolv 1Gal $88.86 (Pack of 4) [CAL433008] Truck Delivery HAZMAT 6.5L x 6.5W x 13H 9.88 LB 0.32 Cubes

Gemini and Agena Model 1/48 Scale $729.95 Gemini and Agena Model 1/48 Scale This custom model is a 1/48 scale of the Gemini Spacecraft and Agena target vehicle.The Agena target vehicle was a spacecraft used by NASA during its Gemini program to develop and practice orbital space rendezvous and docking techniques in preparation for the Apollo program lunar missions.Each ATV consisted of an Agena spacecraft built by Lockheed and a docking adapter built by McDonnell. The Agena was launched from Cape Canaveral Air Force Station Launch Complex 14 on top of an Atlas booster built by the Convair division of General Dynamics. The Agena first burn would occur shortly after shroud jettison and separation from the Atlas over the Atlantic Ocean. Over Ascension Island, a second burn would boost the Agena into a low circular orbit. Please allow 3 to 4 months from the time of order to delivery, as these models are custom made upon ordering. No discounts will apply to this model and all sales final

Herpa 500 Scale HE518925 British Airways A320 1500 $39 With the commissioning of the GEUYL July 2011 Airbus the delivery of its 100th. Aircraft: Airbus A320. Airline: British Airways. Registration: No. Scale: 1:500.

Extra Wide Talking Scale $49.99 A full 15" wide, the tempered glass base has a 550 lb. capacity. This multi-feature "smart" device has tap-on and auto-off capability, a large LCD display, plus a voice function to tell weight. Measures weight in pounds or kilograms. Great for anyone who is visually impaired. Requires one 9V battery (not included). Instructions enclosed. Import. Express delivery not available.

Scaling up Health Service Delivery $30 This book considers the topic of scaling up from a particular vantage point. The focus is on ways to increase the impact of health service innovations that have been tested in pilot or experimental projects so as to benefit more people and to foster policy and programme development on a lasting, sustainable basis. The book addresses a major failure in the global health and development field: namely, the failure to expand the many successful small-scale pilot or demonstration projects that have been organized around the world so as to benefit larger populations than those initially served. It presents a conceptual framework for thinking about scaling up as well as case-studies from Africa, Asia and Latin America where the potential for expansion was a concern from the very inception of pilot or experimental projects. The case-studies discuss family planning and related reproductive health service interventions as well as other innovations in primary health care. The case-studies presented in this book share a series of common values. They emphasize the imperative to build capacity within the public sector institutions to meet the health needs to the disadvantaged. They highlight the necessity of building a strong sense of both local and national ownership in the identification of priority health needs, the development and testing of local solutions, and the formulation of context-specific strategies for expanding small-scale successes. The book build s upon nearly 15 years of experience with the development and testing, in more than 25 countries around the world, of the Strategic Approach to Strengthening Reproductive Health Policies and Programmes.