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A review of drug delivery systems topical ophthalmic
* 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 valuable body. It is considered the window of the soul. We can appreciate and see the world only with this body. There are many diseases eye that affect the body and can be lost sight of the eyes too. Therefore, many systems ophthalmic drug delivery are available. These are classified as conventional ophthalmic preparations and new systems.Most administration of drugs commonly available are the drops and ointments. But such preparations when they are injected into the alley end quickly consumed outside the orbit of the eye due to rupture of the flow nose and tears flowing. Only a small amount is available for a therapeutic effect resulting dosing1 frequent. Thus, the administration of medicines ineffective in the eye is due to the rapid break back, tearing. drainage and dilution of drugs by tears2.
Administration Topical ocular therapeutics is ideal because of the lower dose requirements compared with the systemic use, the early rapid action and the absence systemic toxicity of topically applied ocular drugs must enter the eye and the penetration is believed to be transcorneal the major route of drug absorption. absorption of the cornea is a much slower process than disposal. For many drugs loss K (elimination rate of the first order) is about 0.5-0.7/min and K absorption (absorption rate of the first order) is about 0.001/min. The sum of these rate constants control the fraction of absorbed dose in the application eye3. Thus, ocular bioavailability can be increased by decreasing K Iossa, or by increasing the uptake of K. The first can be obtained by changing the dosage form and the second eye to formulation of dosage forms containing lipophilic prodrugs eye or the addition of penetration enhancers. Therefore, to optimize the administration topical medications time prolonged eye contact surface of the cornea and better penetration through the cornea is necessary4.
A considerable effort has been made in administering ophthalmic drugs since 1970. The two main attempts approqches improved bioavailability and controlled release delivery of drugs.
Improving bioavailability
topical bioavailability can be improved by optimizing the absorption of drugs and minimizing precorneal precorneal drug loss.
1. Improver Viscosity:
To prolong the precorneal residence time and improve the bioavailability attempts were made to increase the viscosity of the formulation. The viscosity enhancers are used hydrophilic polymers such as cellulose, and acid polyacrylic polyol. carboxymethylcellulose sodium is one of the polymers with the largest single accession strength5 mucoadhesive. The effects of polyacrylic acid polyacrylamide hydrogel core are tested in miotic
pilocarpine response. Carbomer were used in liquid and semi-solid suspension or agents increasing the viscosity. cream formulations, including gels and ointments eyes were used as products6. Polycarbophil, an insoluble in water using crosslinked polyacrylic acid to maintain the system of drug delivery because of the binding strength of hydrogel and mucoadhesive eye7. Hyaluronic acid provides a biocompatible matrix and biodegradable materials for the manufacture of sustained release dosage forms of the eye dosage form of esters of hyaluronic acid benzyl used a sustained release of Ophthalmology methylprednisolone. 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 the formulation of the product starts ophthatmic "lunotions are simple for the patient comfort and instead of improve viscosity bioadhesion. viscosity of vehicles increases the contact time and not have marked effect is observed.
2. Gels:
gel formation is an extreme case of improving the viscosity by the use of viscosity enhancers. Thus dosing frequency 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 a vehicle for ophthalmic delivery of pilocarpine and found that the gel formation increases the activity of pilocarpine10. timolol maleate system of drug distribution thermogelling ethylhydroxylethylcellulose11 cellulose ether compound. Effect drug anti-inflammatory effect of flurbiprofen, formulated in carbopol 940 and F 127 pluronic hydrogels were compared in hypertensive eyes. 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 impaired vision and eyelid milkshake that significantly reduce the acceptability of the patient. Sterilization is another disadvantage for the large-scale
3. penetration enhancers:
Work by increasing the absorption of the cornea by changing the integrity of the epithelium cornea. Chelating agents, preservatives, surfactants and bile salts have been studied as improved penetration possible. But the effort has been reduced because of toxicity associated with local enhancers12. penetration enhancers have also been reported to reduce the size of conventional eye drop solutions especially if they cause local irritation.
4. Prodrugs:
Prodrugs to improve drug permeability of the cornea by a modification of the hydrophilic or lipophilic the drug13. The method involves modifying the structure chemical molecule drugs, which in fact is selective and site-specific secure ocular drug delivery. Drugs with greater penetration of the formulations are prodrug epinehrine13, phenylephrine, timolol, pilocarpine14 and salbutamol.
5. Cyclodextrins:
Act cyclodextrins as carriers for keeping the solution hydrophobic drug molecules and deliver them to the surface of the biological membrane, where the relatively lipophilic membrane has a much lower affinity for hydrophilic molecules eyclodextrin WO therefore remain in the aqueous vehicle system. optimal bioavailability can be achieved when sufficient cyclodextrin (
6. Bioadhesive polymers:
The bioadhesive polymers16 adhere to the mucin layer covering the conjunctiva and cornea of the eye's surface, which long residence time of a drug in the conjunctival sac. These polymers may be neutral, synthetic or semisynthetic. polyacrylic acid, polycarbophil acid hyaluronic are commonly used synthetic polymers. Chitosan is a vehicle for the formulation of bioadhesive ophthalmic, because it presents general biological properties such as biodegradability and biocompatibility non-toxicity. Because of its positive charge at neutral pH and ionic interaction with negative charges of sialic acid is produced. Xanthan and carrageenan are also described as bioadhesive polysaccharides17.
IMPROVEMENT OF THE RULES OF DRUG DELIVERY
He realized that the ophthalmic delivery system of choice for improving the bioavailability, site-specific delivery and release drugs Suite. Thus, progress has been made in the following areas:
1. In situ gel formation:
Progress has been made on the technology gel lip Development of freezing droppiable. They undergo a phase transition liquid uponjnstillation background eye-de-sac to form a viscoelastic gel, which responds changes18 the environment. Three methods have been used to induce the phase transition at the surface of the eye. This is the change in pH, variations in temperature and the 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 dispersion of polymer low viscosity of water undergoes spontaneous coagulation instillafion after gelation in the conjunctiva cul-de-sac19.
3. Temperature:
In this method, the solution gelation triggered by temperature change. sustained drug delivery can be obtained using a polymer gel solution to change the temperature of the eye. But this decline is characterized by the concentration of high polymers (Poloxamers 25%) 20. Smart methylcellulose hydrogels are other examples.
4. The ionic strength:
In this gelation method of solution is instilled into force by varying the ionic strength. The example is Gelrite. Gelrite is a polysaccharide, gellan gum acetyl low, which forms a transparent gel in the presence of mono or divalent cations. The concentration of sodium in human tears is 2.6 g / L is particularly suitable because of gelation of the material when installed in topical conjunctival sac.
5. Oil in water emulsions:
Phospholipids and PLURONICS were used as emulsifiers. Antioxidants were added to improve their lives. Intraocular pressure which reduces the effect of a single dose, administered topically with an emulsion of pilocarpine lasted 29 h in rabbits compared to the generic solution pilocarpine, which lasted 5 h21. oil in water emulsion is useful to carry water insoluble drugs, which is dissolved in internal oil phase.
6. Colloidal Islands Party:
The potential use of polymer colloidal particles that systems ophthalmic drug delivery began in late 1970. The first two systems studied in the field of hydrogen cellulose acetate phthalate latex systems piloplex pilocarpine. But as the system could not enter commercial development due to various issues which local toxicity, the polymer is not biodegradable and large-scale sterilization.
7. Liposomes:
The use of liposomes as a delivery system for topical ocular drug began in the early stages of research on drug delivery Ophthalmic. But the results have been favorable for lipophilic drugs and hydrophilic non-drug cons. It was concluded that the liposomes should be suitable for drug delivery eye, has always had an affinity for, and were capable of binding to the ocular surface, and the optimum content rates22 statement. positively charged liposomes have a greater affinity, increase both the conservation of drugs and drug bioavailability precorneal. The addition of stearylamine in a liposomal preparation increased the absorption of the cornea dexamethyl valerate. Epithelium of the cornea is a thin coating of negatively charged mucin which the positive surface charge of liposomes can absorb more force. bioadhesive polymer coating to liposomes, to prolong the retention of liposomes precoma. 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 carbopal lipueme more bioadhesive POLYMAT retention Ilka of the cornea followed by a sustained application of topical cyclosporine eye on crops in an olive oil encapsulated in liposomes and shield cellophane showed slow release of the property.
8. Nanoparticles:
The nanoparticles provide a sustained release and prolonged therapeutic activity to preserve the deadlock after drug administration topical medication should be released from particles trapped in a rate case. To improve the retention of particles, is suitable for the manufacture of particles bioadhesive materials. Biodegradation is also a very desirable property for the manufacture of nanoparticles. The most commonly used are venous cyanoacrylate polymer poly (alkyl), poly-caprolactone S and polylactic acid hydrolysis-co-glycolic being in tears. Coating of polymeric nanoparticles bioadhesive improves bioavailability. chitosan-coated nanocapsules bioavailability27 improve. Nanoparticles as drug delivery ophthalmic It has been shown to be both hydrophilic and hydrophobic drugs28-29.
9. Miarcipartlauldles:
Drugs containing micron size polymer particles suspended in a liquid medium. Medications may be physically dispersed in the polymer backbone30. The drug is released deadlock through dissemination of chemical reaction, and degradation of the polymer and micro-particles are larger than the nanoparticles. Aciclovir microspheres31 chitosan loaded and loaded albumin or gelatin pilocarpine microspheres32 available. microparticle technology has the advantage greater acceptance by the patient, because they can be administered topically to one eye drop33. However, manufacturing and testing of large-scale production of sterile micro particles is very difficult and expensive.
10. Insert:
inserts solids were introduced on the market 50 years ago. Inserting solid was first described in 1948 in the British Pharmacopoeia. He a booklet that contains gelatin and atropine in 1980, many systems have been developed using different principles and polymorphism drug release controlled release of different drugs.
inserts are insoluble polymer systems incorporating the drugs as a solution or dispersion21. Ophthalmic inserts (ocuserts) have been reported with salts of alginate, PVP, collagen and modified by HPC OCUFA is an elastomer silicone matrix which allows controlled release of an active ingredient for a period of at least two weeks22. Inserts also osmotically controlled have been described, where the rejection by diffusion and osmosis controlled4.
Soluble inserts consists of all devices polymers monolytic end of its release, the device will dissolve or erode. Soluble ophthalmic drug inserts a acrylarnide copolymer soluble N-vinyl pyrrolidone and ethyl acrylate. It is a thin film or foil oval sterile. Installation softening in 10-15 seconds after the establishment in the bag top conjuctivall gradually dissolved to 1 pm, while the release of the drug. An insert containing soluble gentamicin sulfate and dexamethasone phosphate was developed for glaucoma pilocarpine also insert were reported. But these systems the disadvantage that they blur vision, while the polymer is dissolved. Bioadhesive formulation soluble in water has been developed to reduce the risk of deportation and ensure long-term residence in the eye, combined with controlled release drugs. bioadhesive drug is inserted eyes. A system based on gentamicin obtained by extruding a mixture of polymers, which shows a timer for the release of about 72 h have been reported. Because of the difficulty with self-insertion, foreign body sensation, only integration products and some pharmaceutical manufacturers are mentioned are not actively developing their insertions on the market.
11. implantable systems:
Poly lactic acid and its copolymers with glycolic acid have been widely used as implants. An ocular implant for delivery of ganciclovir in the treatment of cytomegalovirus has also been developed24. The delivery of drugs directly to the retina for over five months. These systems are less popular because they require minor surgery.
12. Minidisc:
Minidisc is a monolithic device type controlled-release matrix, which consists of a disc with a convex contour and a concave surface26 new. The main component is a (a) (4-methacryloxybutyl)-siloxane polydimethyI. Can be made hydrophilic and hydrophobic extension of the release of water permits bath and the water-soluble drugs insoluble.
13. Soft lenses:
The material used is poly-2-hydrosyethylmethacrylate. Their copolymers with PVP are used for vision correction and to maintain and administer a drug. Controlled release can be obtained by binding to the active covalently by linkages31 biodegradable.
14. Niosomes:
success niosomes are reported as ophthalmic carriers. niosomes discoid dscomes timolol maleate has been reported as promising systems for the administration controlled water soluble drugs20 eye. The shape allows a better adjustment disc in the back of the eye and can prevent large the rejection of their watersheds in the systemic pool.
15. Pharmacosomes:
The vesicles formed by amphiphilic drugs. Any drug that has a free carboxyl group or an active hydrogen atom (-OH,-NH2) may be esterified to the hydroxyl group of a lipid molecule, thereby generating an amphiphilic prodrug. These pharmacosomes be diluted with water. The show greater stability, ease of transport through the cornea and a controlled release profile16.
16. Collagen shields:
They are manufactured 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 medications are charged with protecting the collagen by simply soaking in the drug solution. Providing a layer of collagen solution that lubricates the eye. collagen shields presoaked in tobramycin is used to treat Pseudomonas aeruginosa infected cornea excoriation28. But weapons do are not fully transparent, which reduces the visual activity. But adequate systems of distribution of drugs, both hydrophilic and hydrophobic properties with low penetration.
RECENT
New delivery system includes inserts ophthalmic eye screens collagen films eye, disposable contact lenses and other new delivery systems and controlled hiosomes20 as nanoparticles29. more recent trend is a combination of drug delivery technologies to improve the therapeutic response of a effective drug, no. This may give a higher dose form for topical ophthalmic.
ABSTRACT
These drug delivery systems, only a small number of products have been marketed. An ideal system should have the drug concentration effective in the target tissue for a period of time, usually with minimal systemic effects. patient acceptance is very important for designing a convenient system management ophthalmic drugs. Significant improvements are needed in each system, such as improving sustained drug delivery to the manufacturing scale and stability. The combination of drug delivery systems could open a new directive to improve the therapeutic response of a system of non-effective. They can overcome the limitations and combine the advantages of systems.
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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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