Novel approach of OPTHALMIC DRUG

DELIVERy SYSTEMS

Under the Esteemed Guidance of Dr.B.VasudhaDepartment of Pharmaceutics

Presented By P.Jeevan ReddyRoll no:12H61S0320Pharmaceutics(Shift-1)

CONTENTSINTRODUCTION ANATOMY OF EYE BARRIERS FOR OCULAR DDSCLASSIFICATION TYPES OF OCULAR DDS GENERAL SAFETY CONCERNS ADVANCES IN OCULAR DDS EVALUATION METHODS CONCLUSION REFERENCES

INTRODUCTION

Traditionally used eye drop formulations lacked good bioavailability and had low patient compliance, hence most investigations in this field emphasize on the duration of action and enhancement of corneal absorption

Recent developments in ophthalmic drug delivery systems include use of gelling polymers, prodrugs, microspheres, nanoparticles, liposomes and hydrophilic ocular inserts. Protein and peptide delivery, posterior drug delivery and non-aqueous vehicles are new areas of interest in ophthalmic drug delivery.

• The Ophthalmic Drug Delivery Systems (ODDS) are desired to improve efficacy, minimization of toxicity, sustained effect or modified drug release.

• Cyclodextrin cyclic oligosaccharides are the newer carriers in ODDS which have proved to be useful for controlled release by forming a complex which is known to show rapid and quantitative drug release.

RELEVANT ANATOMY AND PHYSIOLOGY OF THE EYE

• HUMAN EYE :    The accessory structures of the eye are the eyelids, eyelashes, eyebrows, the lachrymal apparatus and extrinsic eye muscles. The diameter of eye is 23mm. 

         General Pathway For Ocular Absorption 

BARRIERS FOR OCULAR DELIVERY

 Drug loss from the ocular surface after instillation, the flow of lacrimal fluid removes instilled compounds from the surface of the eye.

Even though the lacrimal turnover rate is only about 1 μl/min the excess volume of the instilled fluid is flown to the nasolacrimal duct rapidly in a couple of minutes.

Another source of non-productive drug removal is its systemic absorption instead of ocular absorption.

Systemic absorption may take place either directly from the conjunctival sac via local blood capillaries or after the solution flow to the nasal cavity.

Approaches to improve ocular bioavailability

1) Viscosity enhancers 8) Eye ointments

2) Gel 9) Prodrug

3) Penetration enhancers 10) Liposomes

4) Niosomes 11) Nanosuspension

5) Microemulsion

6) Nanoparticles/nanospheres

7) In situ-forming gel

Classification Of Ophthalmic Dosage Form:

1)Based on route of administration:a)Topical solution

b)Intra ocular solution

c)Opthalmic solution

2)Based on physical form: a)Aqueous solutions

b)Suspension

c)Ointments

d)Gels

e)Eye lotions

f)Solid inserts

        TYPES OF OCULAR DRUG DELIVERY

A)Non-erodible:1)Ocusert

2)Contact lenses

3)Diffusional inserts

B)Erodible1)Lacrisert

2)Soluble ocular drug inserts(sodi)

3)Minidisc

4)Nanoparticles

5)Liposomes

Role Of Polymer In ODDS Solution Viscosity , Solution Drainage. Polymer

Mucoadhesive Vehicle: Retained in the eye due to non-covalent bonding between with conjuctival mucine. Mucine is capable of picking of 40-80 times of weight of water

Polymeric Solution: The addition of polymers like methylcellulose, polyvinyl alcohol, hydroxypropyl cellulose and polyvinyl pyrrolidone to the eye drop solution increases the corneal penetrations of drug.

• This is presumably due to on increases tear viscosity, which decreases the other wise rapid initial drainage rate, increases the corneal contact time and thus sustains to some extant the initial tear concentration of the drug.

Manufacturing Environment:

General safety considerationsa) Sterility:

b) Ocular toxicity and irritation

Preservatives and preservation

LIMITATIONS OF CONVENTIONAL DRUG DELIVERY

Rapid precorneal elimination

Solution drainage by gravity

Frequent instillation is necessary

Conjuctival absorption

                                    

ADVANTAGES OF AVANCED DUG DELIVERY

Sustained and/or controlled drug release

Site-specific targeting

Protect the drug from chemical or enzymatic hydrolysis

Increasing contact time and thus improving bioavailability

Better patient compliance.

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Advances in Ophthalmic Drug Delivery Systems

IN-SITU GELS -A NOVEL APPROACH FOR OCULAR DRUG DELIVERY  

• Polymeric gels for improved drug delivery.-HYDRO GEL

• Ophthalmic inserts :are defined as sterile solid or semisolid preparations, with a thin, flexible and multilayered structure, for insertion in the conjunctival sac.

Ocular iontophoresis:     Iontophoresis is the process in which direct current

drives ions into cells or tissues .

      Evaluation of ocular drug delivery systems

Ocular drug delivery systems are evaluated by various methods. The ocular in-vitro studies include design of specialised apparatus.

The ocular in-vivo studies were done in rabbits and include tear pH measurements, pharmacodynamic studies and scintigraphy to assess precorneal residence of formulations.

In-vitro evaluation methods :A number of approaches are used by different workers to conduct in-vitro evaluation of controlled ocular drug delivery systems.

   (a) Bottle method (b) Diffusion method (c) Modified rotating basket method (d) Modified rotating paddle apparatus (e) Flow through devices

(2) In – vivo evaluation methods The controlled ocular drug delivery systems can be

evaluated for its pharmacokinetic and pharmacodynamic profiles.

The main objective of the pharmacokinetic studies is to determine the drug release from the dosage form to the eye. Rabbit is used as an experimental animal because of a number of anatomical and physiological ocular similarities and also due to larger size of the eye .

• Equipments:The blow /fill/seal method:

Marketed productsGlucotim LA of Centaur Pharma is an original research

formulation of Timolol .Used to treat Glaucoma.

Combigan contains brimonidine. Combigan is used to

treat glaucoma or ocular hypertension

ConclusionIn the past 2 decades, a considerable amount of

research has been carried out on the development of ocular drug delivery systems.

It is appreciated that the topical route is preferred for delivery of drugs to the eye. 

The primary objective of all the ocular drug delivery systems developed till date is to increase ocular drug residence time which leads to improvement in ocular drug bioavailability, diminish side effects due to systemic absorption and diminishing the necessary amount of drug for a therapeutic response in the eye.

References

1.Hill J M, O' Callaghan R J, Hobden J A, Kaufman H E. Corneal Collagen shields for ocular delivery. In :Mitra A K, eds. Ophthalmic drug delivery systems, New York: Marcel Dekker Inc., 1993; 261 – 273.

2.Hughes P M, Mitra A K. Overview of ocular drug delivery and iatrogenic ocular cytopathologies. In : Mitra A K, eds. Ophthalmic drug delivery systems, New York: Marcel Dekker Inc., 1993; 1-28.

3.Van Ootegham M. M M. Fomulation of ophthalmic solutions and suspensions. In : Edman P, eds. Biopharmaceutics of ocular drug delivery, Boca Raton : CRC press, 1993; 27-42.

4.Mueller W H, Deardroff D L. Ophthalmic vehicles: The effect of methyl cellulose on the penetration of Homatropine hydrobromide through the cornea. J. Am. Pharm. Assoc. 1956; 45: 334.

5.Krishna N, Brown F. Polyvinyl alcohol as an ophthalmic vehicle. Am. J. Ophthalmol. 1964; 57: 99.

6.Swanson A A, Jeter D J, Tucker P. Ophthalmic vehicles II. Comparison of ointment and polyvinyl alcohol 1.4% . Ophthalmologica. 1970; 160: 265 - 270.

QUERIES…..

“Sight is the sense which is more valuable than all the rest.” So Take care of Eyes!!!