APPROACHES OF DRUG DELIVERY TO EYES

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CONTENTS

• INTRODUCTION• ANATOMY AND PHYSIOLOGY OF EYE• BARRIERS• FORMULATION CONSIDERATIONS• IDEAL CHARACTERISTICS• DRUG DELIVERY SYSTEMS• EVALUATION• ADVANTAGES AND DISADVANTAGES• CONCLUSION• REFERENCES

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INTRODUCTION• Eye diseases are commonly encountered in day to day life,

which are cured or prevented through the conventionally used

dosage forms like eye drops, ointments, etc., Ocular drug

delivery systems are intended for installation into the cul-de-sac,

i.e., the space between the eye ball and the eye lids. Delivery to

the internal parts of the eye still remains troublesome due to the

anatomical and protective structure of the eye. Drugs may be

delivered to the eye through the application of four primary

modes of administration: topical, systemic, intravitreal, and

periocular.

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ANATOMY AND PHYSIOLOGY OF EYE

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BARRIERS FOR DRUG ABSORPTION

•Tears

•Cornea

•Conjuctiva

•Sclera

•Retina

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FORMULATION CONSIDERATIONS

•Physicochemical characteristics of drug and

polymers.

•Buffering capacity and pH.

• Instillation volume.

•Osmotic pressure.

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Ideal characteristics of ocular drug delivery system

• Good corneal penetration.

• Prolong contact time with corneal tissue.

• Non irritative and non toxic.

• Good rheological properties.

• Non greasy

• Patient compliance.

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8DRUG DELIVERY SYSTEMS TO EYE:

IMPLANTSDENDRIMERSIONTOPHORESISMICROEMULSIONMICRONEEDLENANOSUSPENSIONCONTACT LENSES

1.CONVENTIONAL SYSTEMS

• EYE DROPS: To prolong the retention time of

topically applied drugs, anterior DDSs for eye-

drops utilizing interaction between drug carrier

(excipients) and physiological environment of

cornea and/or sub-conjunctiva are being developed.

These are administered in the form of Solutions,

Emulsion and Suspension eye drops and are used

only for anterior segment disorders.

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•OINTLENTS AND GELS

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Prolongation of drug contact time with the external ocular surface can be achieved

using ophthalmic ointment vehicle but, the major drawback of this dosage form like,

blurring of vision and blinking of eyelids can limits its use. These products will stay on

eyes longer than eye drops.

•INSERTSOcular insert are sterile preparation that prolong residence time of drug with a

controlled release manner and negligible or less affected by naso-lacrimal damage. The

ocular inserts maintain an effective drug concentration in the target tissues and yet

minimize the number of applications.

2.VESICULAR SYSTEMS• LIPOSOMES: Liposomes are vesicles composed of lipid membrane

enclosing an aqueous volume. These structures are formed simultaneously

when a matrix of phospholipids are agitated in an aqueous medium to

disperse the two phases. They are having an intimate contact with the

corneal and conjunctival surfaces which is desirable for drugs that are

poorly absorbed.

• NIOSOMES AND DISCOMES : Niosomes are nonionic surfactant

vesicles that have potential applications in the delivery of hydrophobic or

amphiphilic drugs. Discomes are discoidal vesicles and may act as

potential drug delivery carriers by releasing the drug in a sustained manner

at the ocular site.

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•PHARMACOSOMES: Drugs possessing a free carboxyl group or an active

hydrogen atom can be esterified to the hydroxyl group of a lipid molecule, thus

generating an amphiphilic prodrug. This amphiphilic prodrug is converted to

pharmacosomes on dilution with water. pharmacosomes show greater shelf stability,

facilitated transport across the cornea, and a controlled release profile.

3.CONTROLLED RELEASE

• IMPLANTS: implants are effective drug delivery system for chronic

ocular diseases like cytomegalovirus (CMV), retinitis. Intravitreal implants

of fluocinolone acetonide were developed for the treatment of posterior

segment.

• DENDRIMERS: Dendrimers are repetitively branched molecules and can

be successfully used for ocular drug administration and have better water-

solubility, bioavailability and biocompatibility.

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•IONTOPHORESIS: Iontophoresis is a noninvasive technique for ocular drug

delivery. In iontophoresis the drug solution is in contact with the cornea in an eye-cup

bearing an electrode and the diffusion of drug occurs by electrical potential

difference.

•MICROEMULSION: Microemulsion is dispersion of water and oil stabilized using

surfactant and co-surfactant to reduce interfacial tension and usually characterized by

small droplet size(100 nm), higher thermodynamic stability and clear appearance.

They reduce the frequency of administration as compared to the conventional systems.

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•NANOSUSPENSION: Nanosuspensions have emerged as a promising strategy

for the efficient delivery of hydrophobic drugs because they enhanced not only

the rate and extent of ophthalmic drug absorption but also the intensity of drug

action with significant extended duration of drug effect.

•CONTACT LENSES: Water soluble drugs soaked in drug solutions can be

absorbed through Contact lenses. The drug saturated contact lenses are placed in

the eye which releases the drug in eye for a long period of time. For prolongation

of ocular residence time of the drugs, hydrophilic contact lenses can be used.

4.PARTICULATE SYSTEMS (NANOPARTICLES AND MICROPARTICLES)

• Nanoparticles are prepared using bioadhesive polymers to provide

sustained effect to the entrapped drugs. An optimal corneal penetration of

the encapsulated drug was reported in presence of bioadhesive polymer

chitosan.

• Microemulsions have a transparent appearance, with thermodynamic

stability and a small droplet size in the dispersed phase (aqueous and

nonaqueous phase) (<1.0μm). Microspheres of poly lacto gylcolic acid

(PLGA) are prepared for topical ocular delivery.

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5.ADVANCED DRUG DELIVERY SYSTEMS

• Several kinds of viruses including adenovirus, retrovirus,

adeno-associated virus, and herpes simplex 140virus, have

been manipulated for use in gene transfer and gene therapy

applications. The advanced delivery systems such as gene

delivery, SiRNA, stem cells that prolong the contact time of

the dosage form with the surface of the eye and facilitate non-

invasive administration.

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Evaluation of ocular drug delivery system

• Thickness of the film.

• Drug content.

• Irritancy test.

• Percentage moisture loss.

• In vitro drug release.

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ADVANTAGES• Localized drug delivery is possible.

• Drops are easy to apply and have good patient acceptance.

• Intravitreal , periocular sub-conjuctival injections improve drug absorption

and have no systemic toxicity.

• Micro particles , Nanoparticles, liposomes increase half life of drug.

• ocular inserts increased ocular residence releasing drugs

at a slow and constant rate.

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DISADVANTAGES

•Physical instability of the dosage form.

•Frequent administration reqired with conventional

systems.

•Leaking of entrapped drug.

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CONCLUSION

• Ocular drug delivery systems provide local as well as

systemic delivery of the drugs. The novel advanced

delivery systems offer more protective and effective

means of the therapy for the nearly inaccessible

diseases or syndromes of eyes. Further developments

are preferable which will eliminate the cons of these

available advanced delivery systems and readily

acceptable with the regulatory authorities as well.

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REFERENCES

• Text book of pharmaceutical sciences by Remington.

• Novel and controlled drug delivery by N.K Jain.

• Patel Vishal, Agrawal Y.K. CURRENT STATUS AND

ADVANCED APPROACHES IN OCULAR DRUG DELIVERY

SYSTEM, Journal of Global Trends in Pharmaceutical

Sciences, Vol.2, Issue 2, pp -131-148.

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