Lens Pen Silicon

Lens Pen Silicon

A review of systems topical ophthalmic drug delivery

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

1B. N. Girls College of Pharmacy, Udaipur

2Rishiraj Faculty of Pharmacy, Indore

3B.N. Faculty of Pharmacy, Udaipur

Eye is unique and precious organ. It is considered the window to the soul. We can enjoy and see the world only with this body. There are many eye diseases that affect the body and can be lost eye sight too. Therefore many of the systems for ophthalmic drug delivery are available. These are classified as ophthalmic preparations conventional and new drug delivery systems.Most commonly available are the drops and ointments. However, these preparations when instilled into the alley end quickly consumed outside the eye socket due to rupture of nasal flow and tear flow. Only a small amount is available for therapeutic effect resulting in frequent dosing1. So ineffective drug administration in the eye occurs due to rapid break back, tear. drainage and dilution of drugs by tears2.

Topical administration for ocular therapeutics is ideal due to lower dose requirements compared with the systemic use, the beginning rapid action and lack of systemic toxicity of topical ocular drugs must penetrate into the eye and the penetration is transcorneal believed to be the main route for drug absorption. absorption of the cornea is a much slower process than elimination. For many drugs loss K (first-order elimination rate) is about 0.5-0.7/min and K absorption (first-order absorption rate) is approximately 0.001/min. The sum of these two rate constants control the fraction of absorbed dose in the application eye3. So the ocular bioavailability can be increased by decreasing K IOSS, or by increasing the uptake of K. The first can be achieved by changing the ocular dosage forms and the second through the formulation of dosage forms containing eye lipophilic prodrugs or adding penetration enhancers. Therefore, to optimize the administration of topical ocular drug contact time Prolonged surface of the cornea and better penetration through the cornea is necessary4.

A considerable amount of effort has been made in the administration ophthalmic drugs since 1970. The two main approqches attempts are improved bioavailability and controlled release delivery of drugs.


topical bioavailability can be improved by maximizing precorneal drug absorption and minimize loss precorneal drug.

1. Improver Viscosity:

In order to prolong the precorneal residence time and improve the bioavailability of attempts were made to increase the viscosity of the formulation. The viscosity enhancers are used hydrophilic polymers such as cellulose, and polyacrylic acid polyol. sodium carboxymethyl cellulose is one of the most important polymers having mono adhosive strength5 mucoadhesion. The effects of polyacrylic acid and polyacrylamide based hydrogels are tested in miotic
pilocarpine response. Carbomer were used in liquid and semisolid formulations as suspending or increased viscosity agents. Formulations including creams, eye gels and ointments were used as products6. Polycarbophil, a water insoluble cross-linked polyacrylic acid assistance in maintaining the drug delivery system due to the bonding strength of hydrogel and mucoadhesive eye7. Hyaluronic acid provides a biocompatible matrix and biodegradable materials for the manufacture of dosage forms of ocular sustained release dosage form-based hyaluronic acid esters used benzyl for sustained release of methyl prednisolone ophthalmic. Films and microspheres were prepared from hyaluronic acid. Polysaccharide such as xanthan gum was found to increase viscosity8. Today, hydrophilic polymers are also used in product formulation ophthatmic Departures "are simple lunotions for patient comfort and instead of improving bioadhesion viscosity. vehicles viscosity increases the contact time and not hold marked effect is seen.

2. Gels:

gel formation is an extreme case of viscosity improvement through the use of viscosity enhancers. So the frequency of dosing can be reduced to once a day9. Cellulose acetate phthalate dispersion is a system of micro-reserves of high viscosity. Poloxamer 407 is used as an ophthalmic vehicle for delivery of pilocarpine and found that the formation of gel increases the activity of pilocarpine10. form timolol maleate drug delivery system thermogelling ether compound ethylhydroxylethylcellulose11 cellulose. The effect of flurbiprofen an anti inflammatory drugs, formulated in carbopol 940 and F 127 pluronic hydrogels were compared in hypertension eye. Gelrite is a polysaccharide (Gellen gum), which forms a transparent gel in the presence of mono or divalent cations. The high viscosity of the gel, however, is of blurred vision and eyelid milkshake that substantially reduce patient acceptability. Sterilization is another drawback for large-scale production,

3. Penetration enhancers:

Work by increasing the absorption of the cornea by changing the integrity of the epithelium corneal. Chelating agents, preservatives, surfactants and bile salts were studied as possible penetration improvement. But the effort was reduced due to toxicity associated local with enhancers12. penetration enhancers have also been reported to reduce the size of conventional eye drop solutions especially if they cause irritation local.

4. Prodrugs:

Prodrugs improve corneal drug permeability through modification of the hydrophilic or lipophilic of the drug13. The method includes modifying the chemical structure of the drug molecule, which makes is selective and site-specific secure system of ocular drug delivery. Drugs with greater penetration through prodrug formulations are, epinehrine13, phenylephrine, timolol, pilocarpine14 and salbutamol.

5. Cyclodextrins:

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

6. Bioadhesive polymers:

The bioadhesive polymers16 adhere to the mucin layer covering the conjunctiva and cornea of the eye surface, which prolonged residence time of a drug in the conjunctival sac. These polymers may be neutral, synthetic or semisynthetic. Polyacrylic acid, acid hyaluronic polycarbophil are commonly used synthetic polymers. Chitosan is a bioadhesive vehicle for ophthalmic formulation, since it presents general biological properties such as biodegradability, and biocompatibility nontoxicity. Due to its positive charge at neutral pH and ionic interaction with negative charges sialic acid is produced. Xanthan and carrageenan are also described as bioadhesive polysaccharides17.


He realized that the ophthalmic delivery system of choice to improve the bioavailability, site-specific delivery and release Continued drug. So the achievements have been made in the following areas:

1. In situ gel formation:

Progress has been made on the lip gel technology for the development of droppiable gel. Uponjnstillation are fluid and subject to the phase transition in the background eye-de-sac to form visco-elastic gel, which provides a response to environmental changes18. Three methods have been used to cause the phase transition on the surface the eye. These are the change in pH, temperature change and activation of ions.

1. PH:

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

3. Temperature:

In this method the solution gelation triggered by the change in temperature. sustained drug delivery can be achieved by using a polymer changing solution to gel at the temperature of the eye. But downside of this is characterized by high polymer concentration (25% poloxamers) 20. methyl cellulose hydrogels Smart are other examples.

4. Ionic strength:

In this method of gelation of the solution is instilled active by the change in the ionic strength. The example is Gelrite. Gelrite is a polysaccharide, low-acetyl gellan gum, which forms a transparent gel in the presence of mono or divalent cations. The sodium concentration in human tears is 2.6 g / l is particularly suited to cause gelation of the material when topically installed in conjunctival sac.

5. Oil in water emulsions:

Phospholipids and pluronics were used as emulsifiers. Antioxidants were added to improve their life. Intraocular pressure which reduces the effect of a single dose, administered topically with an emulsion of pilocarpine lasted for 29 h in rabbits compared with pilocarpine generic solution that only lasted 5 h21. oil in water emulsion is useful to deliver water insoluble drugs, which is solubilized in the internal oil phase.

6. Colloidal part Iles:

The potential use of polymeric colloidal particles as delivery systems for ophthalmic drugs began in late 1970. The first two systems studied in this field of hydrogen phthalate cellulose acetate latex pilocarpine piloplex systems. But both the system could not enter the commercial development due to various issues, as the local toxicity, the polymer is not biodegradable and large-scale sterilization.

7. Liposomes:

The use of liposomes system as a topical ocular drug delivery began in the early stages of research on ophthalmic drug delivery. But the results were favorable for lipophilic drugs and hydrophilic non-for-drugs. It was concluded that the liposomes should be suitable for drug delivery eye, always had an affinity for, and were capable of binding to the ocular surfaces, and the optimum content of rates22 release. positively charged liposomes have a greater affinity to increase both the precorneal drug retention and bioavailability of drugs. The addition of stearylamine to an intensification of the liposomal preparation absorption of the cornea dexamethyl valerate. The corneal epithelium is thin coated negatively charged mucin to which the positive surface charge of liposomes can be absorbed harder. Bioadhesive polymer coating to liposomes, to prolong the retention of liposomes precomea. Carbopol 1342-coated liposomes containing pilocarpine23 shown to produce a longer duration of action. acetazolamide24 liposomal preparation, hydrocortisone25 tropicamide26 and has been reported. Coating with POLYMAT lipueme Ilka carbopal bioadhesive greater retention of the cornea followed by a sustained action cyclosporine topically applied eye on oil crops Olive in an encapsulated form in liposomes and in a cellophane shield showed slow release of the property.

8. Nanoparticles:

Nanoparticles provide a sustained release and prolonged therapeutic activity to be retained in the dead-end after topical administration and the drug must be released trapped particles in a rate case. To improve the retention of particles, is suitable for the manufacture of particulate materials bioadhesive. Biodegradation is also a very desirable property for the manufacture of nanoparticles. Most commonly used are intravenous polymers poly (cyanoacrylates alkyl), poly-S caprolactone and polylactic acid-co-glycolic undergoing hydrolysis in tears. Coating of nanoparticles with bioadhesive polymers improving bioavailability. chitosan-coated nanocapsules bioavailability27 improve. Nanoparticles as ophthalmic drug delivery has been shown both hydrophilic and hydrophobic drugs28-29.

9. Miarcipartlauldles:

Are drugs that contain micron-sized polymer particles suspended in a liquid medium. Drugs can be physically dispersed in the polymer backbone30. The drug is released in dead output through diffusion, chemical reaction, and degradation of the polymer and micro particles are larger than the nanoparticles. Aciclovir loaded microspheres31 chitosan and pilocarpine-loaded albumin or gelatin microspheres32 available. microparticle technology has the advantage of greater acceptance by patient, because they may be administered topically as an eye drop33. However, the manufacture and control of large-scale manufacture of sterile micro particles is very difficult and expensive.

10. Insert:

Solid inserts were introduced into the market 50 years ago. Insertion solid was first described in 1948 in British Pharmacopoeia. It was a wafer that contains gelatin and atropine in 1980 of numerous systems were developed using various and different polymora early drug release from controlled release of drugs.

inserts are insoluble polymeric systems in which the drug is incorporated as a solution or dispersion21. Ophthalmic inserts (ocuserts) have been reported with alginate salts, PVP, as amended by collagen and HPC, Ocufit is a silicone based elastomer matrix which allows the controlled release of active ingredient over a period of at least 2 weeks22. Osmotically controlled insertions have also been described, where the release is by diffusion and osmosis controlled4.

Soluble inserted monolytic consists of all polymer devices by the end of their release, the device dissolve or erode. Soluble ophthalmic drug inserts a acrylarnide soluble copolymer, N-vinyl pyrrolidone and ethyl acrylate. It is a sterile thin film or sheet oval. The softening system in 10-15 seconds after the introduction into the sack top conjuctivall gradually dissolves in 1 h, while the release of drug. A soluble insert containing gentamicin sulfate and dexamethasone phosphate was developed for glaucoma Insert pilocarpine has also been reported. But these systems have the disadvantage that they blur vision, while the polymer is dissolved. water-soluble component bioadhesive formulation has been developed to reduce risk of expulsion and ensure long-term residence in the eye, combined with controlled release of drugs. Bioadhesive ophthalmic drug inserts. A system based in gentamicin obtained by extrusion of a polymer blend, which shows a timer for the release of about 72 h has been reported. Because of the difficulty with auto-insertion, foreign body sensation, only a few products listed and pharmaceutical insertion manufacturers are actively developing inserts for marketing.

11. implantable systems:

The poly lactic acid and its copolymers with glycolic acid have been widely used as implants. An ocular implant for delivery of ganciclovir to treat cytomegalovirus has been developed24. The delivery of drugs directly to the retina for more than 5 months. These systems are less popular because they require minor surgery.

12. Minidisc:

Minidisc is a monolithic controlled release device type matrix, which consists of a contoured disk with a convex and concave face a new surface26. The main component is A (1) bis (4-methacryloxybutyl)-siloxane polydimethyI. Can be made hydrophilic and hydrophobic extension of the permit release of water from the tub and soluble water-insoluble drugs.

13. Soft contact lenses:

The material used is poly-2-hydrosyethylmethacrylate. Their copolymers with PVP are used for vision correction and to sustain and administer medication. Controlled release can be obtained by binding to the active through covalent linkages31 biodegradable.

14. Niosomes:

Niosomes success are reported as ophthalmic carriers. niosomes discoidal dscomes timolol maleate has been reported that promising systems for the controlled administration of water soluble drugs20 eye. The form provides better disk adjustment in the eye fundus and then large can prevent the release of their watersheds in the systemic pool.

15. Pharmacosomes:

Vesicles are formed by amphiphilic drugs. Any drug that has a free carboxyl group or an active hydrogen atom (-OH,-NH2) can be esterified to the hydroxyl group of a lipid molecule, thus generating a amphiphilic prodrug. These become pharmacosomes diluting with water. Them show greater stability, facilitated transport across the cornea and a controlled release profile16.

16. Collagen shields:

They are made from porcine scleral tissue, which has a composition similar to that of collagen in the human cornea. They are hydrated before being placed in the eye and drugs are loaded with collagen shield simply by soaking it in the drug solution. Provide a layer of collagen solution that lubricates the eye. collagen shields presoaked in tobramycin is used to treat Pseudomonas aeruginosa excoriation28 infected cornea. But the arms are not fully transparent, thereby reducing visual activity. But are adequate systems of delivery of drugs, both hydrophilic and hydrophobic with poor penetration properties.


New ophthalmic delivery system includes ocular inserts, collagen shields, ocular films, disposable contact lenses and other new delivery systems hiosomes20 and controlled as nanoparticles29. more recent trend is a combination of drug delivery technologies to improve the therapeutic response of an effective drug not. This can give a higher dosage form for topical ophthalmic application.


These drug delivery systems, only a few products have been marketed. An ideal system must have effective drug concentration in the target tissue for a period of time tended with minimal systemic effects. patient acceptance is very important for the design of any convenient system management ophthalmic drugs. Major improvements are required in each system, as the sustained improvement in drug delivery, manufacturing scale and stability. The combination of drug delivery systems could open a new directive to improve the therapeutic response of a non-effective system. They can overcome the limitations and combine the advantages of different systems.


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

2. Bharath, C. and Hiremath. SR., Pharmazie, 1999, 51, 55.

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

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

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

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

7. Durrani AM, Farr, SJ and Kellaway. IW. J. Pharm. Pharmacol., 1995, 47, 581.

8. Gazayerly, EL, Omaima. N. and Hikal. AH. J. Int Pharm. 1997. 158,121.

9. Hui. HW and Robinson, JR, Int J. Pharm., 1985. 26, 203.

10. Kamal S. Rathore, Dr. RKNema, "Glaucoma: A Review", published online in www.earticlesonline.com (Jan4 , 2009).

11. Kaur, IP and Smith. R. Developing drugs. Ind. Pharm., 2002 28. 353.

12. Keistea, JC, Cooper ER, Missel, PJ, Long, JC and Hager, DF J. Pharm. Sci, 1991, 80, 50.

13. Khopade, AJ and Jain, NK Pharmazie, 19%. 50, 812.

14. Kumar, S., Haglund, BO and Himmelstein, KJ, J. Hidden. Pharmcol., 1994,10,47.

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

16. F. Latorre and Nicolai, AP, Exp Drug Clin, Res .. 1998, 24, 153.

17. Lee, VHL and Robinson, JR, J. Hidden. Pharmacol., 1986, 2, 67.

18. Lin. Human resources and Sung. KC, J. Contol. release 2000, 69, 379.

19. LnduPal. K. and Meenakshi, K., Drug Development. Ind. Pharm., 2002, 473.

20. Marshall. WAS and Klyee, SD, 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, DL, Leung, SHS and Robinson, JR, En, Lenaerts, V and Gummy, R., eds., Bioadhesive Drug Delivery Systems, CRC Press, Boca Raton., 1990. 203.

23. Monem AS, Ali FM. and Ismail. MW. Pherma J. Int., 2000 198, 20.

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

25. Rathore KS, Nema RK, Management of Glaucoma: a review "International Journal of Research Pharm Tech, Vol 1, No. 3, pp, July-September 2009.

26. Rathore KS, RK Nema, "an idea Ophthalmic Drug Delivery System," published online in www.ijpsdr.com. June-Aug.2009 issue

27. Rathore KS, Nema RK, "Eye Exam inserted into" International Journal of Pharm Tech Research, Vol 1, No. 2, pp 164-169, April-June 2009.

28. Rathore KS, Nema RK, "The formulation and evaluation of timolol maleate ophthalmic movies" Indica plant, vol.no.4, October-December 2008, p. 49-50.

29. Simamora, P., Nadkarni, SR, Lee, YC and Yalkowsky, SH, Int J. Pharm., 1998, 170, 209.

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

31. Wei, G., Xu, H., Ding, PT, USM and Zheng. JM, J. Control. Release, 2002, 83, 65.

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

33. Zimmer, AK, Chetoni, R. Saettone, MP 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

Lec 35 | MIT 3.091 Introduction to Solid State Chemistry