A Seminar onA Seminar onOCUSERT & CONTACT LENSEOCUSERT & CONTACT LENSE

PRESENTED BY MR. KIRAN N.PATANGE

M.PHARM II SEMISTER (PCEUTICS)DEPT. OF P’CEUTICAL SCIENCES RTMNU

CONTENTS………Introduction

Human eye anatomy

Mechanism of ocular absorption

Factors affecting Intraocular bioavailability

Pharmacokinetics of ocular drug administration

Ophthalmic preparations

Classification of Ophthalmic dosage forms

Advances in ocular drug delivery

Ophthalmic preparations:

• Definition: They are specialized dosage forms designed to be instilled onto the external surface of the eye (topical), administered inside (intraocular) or adjacent (perioccular) to the eye or used in conjunction with an ophthalmic device.

• The most commonly employed ophthalmic dosage forms are solutions, suspensions, and ointments.

• The newest dosage forms for ophthalmic drug delivery are: gels, gel-forming solutions, ocular inserts , intra-vitreal injections and implants.

• Ocular administration of drug is primarily associated with the need to treat ophthalmic diseases.

•Eye is the most easily accessible site for topical administration of a medication.

•Ideal ophthalmic drug delivery must be able to sustain the drug release and to remain in the vicinity of front of the eye for prolong period of time.

INTRODUCTION

Drugs used in the eye:

• Miotics e.g. pilocarpine Hcl

• Mydriatics e.g. Atropine

• Cycloplegics e.g. Atropine

• Anti-inflammatories e.g. corticosteroids

• Anti-infectives (antibiotics, antivirals and antibacterials)

COMPOSITION OF EYE: COMPOSITION OF EYE:

Water - 98%, Solid -1.8%, Organic element – Protein - 0.67%, sugar - 0.65%, NaCl - 0.66% Other mineral element sodium, potassium and ammonia - 0.79%.

Human eyeDiameter of 23 m

Structure comprises of three layers

Outermost coat : The clear, transparent cornea and the white, opaque sclera

Middle layer : The iris anteriorly, the choroid posteriorly, and the ciliary body at the intermediate part

Inner layer : Retina (extension of CNS)

CorneaEpithelium-stroma-endothelium

(fat-water-fat structure)

Penetration of the drug depends on Oil-water partition coefficient

Corneal cross section

Fluid systems in eye-1. Aqueous humor: Secreted from blood through epithelium of the

ciliary body.Secreted in posterior chamber and transported to anterior chamber.

2. Vitreous humor:Secreted from blood through epithelium of the ciliary body.

Diffuse through the vitreous body.

Lacrimal glands:

Secrete tears & wash foreign bodies.

Moistens the cornea from drying out.

BARRIERS IN OCULAR ABSORPTION

Precorneal ConstraintsIt include –• Solution drainage• Lacrimation• Tear dilution• Tear turnover• Conjunctival absorption

Corneal constraints

• Cornea as rate limiting barrier

• Anatomy of cornea

1.Outer-Epithelium(lipophilic),

2.Middle-Stroma(hydrophilic),

3.Inner-Endothelium(lipophilic

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OCULAR ABSORPTION

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OCULAR DELIVERY SYSTEMS

CONVENTIONAL VESICULAR

CONTROL RELEASE

PARTICULATE

SOLUTIONSUSPENTIONEMULSIONOINTMENTINSERTGELS

IMPLANTSHYDROGELSDENDRIMERS

IONTOPORESISCOLLAGEN SHIELD

POLYMERIC SOLUTIONS

CONTACT LENSESCYCLODEXRIN

MICROONEEDLEMICROEMULSIONSNANO SUSPENSION

ADVANCED

SCLERAL PLUGSGENE DELIVERYSi RNASTEM CELLECT

MICROPARTICLESNANOPARTICLES

LIPOSOMESNIOSOMESDISCOMESPHARMACOSOMES

CONTACT LENSES:CONTACT LENSES: These are circular shaped structures. Dyes may be added during polymerization. Drug incorporation depends on whether their

structure is hydrophilic or hydrophobic.Drug release depends upon : Amount of drug Soaking time. Drug concentration in soaking solution.ADVANTAGES: No preservation. Size and shapeDISADVANTAGES: Handling and cleaning Expensive

Contact Lenses & Care Solutions:

• Types of contact lenses:

1- Hard contact lenses.

2- Soft contact lenses.

3- Rigid gas permeable (RGP).

4-Rigid hydrophobic

Contact Lenses & Care Solutions:

1- Hard contact lenses- Made of rigid plastic resin polymethylmethacrylate- Impermeable to oxygen and moisture

2- Soft contact lenses- Made of hydrophilic transparent plastic,

hydroxyethylmethacrylate- Contain 30 – 80% water so are permeable to oxygen- Have two types: daily wear and extended wear

Contact Lenses & Care Solutions:

3- Rigid gas permeable (RGP)- Take the advantages of both soft and hard lenses,

they are hydrophobic and oxygen permeable.

Advantages of hard contact lenses and RGP lenses:1- strength durability2- resistant to absorption of medications and

environmental contaminants3- visual acurity Disadvantages:1- require adjustment period of the wearer2- more easily dislodged from the eye

Contact Lenses & Care Solutions:

• Advantages of soft contact lenses:

1- worn for longer periods

2- do not dislodge easily

Disadvantages:

1- have a shorter life span and the wearer must ensure that the lenses do not dry out

• Contact Lens Classes,characteristcs & Support Product LENS TYPE POLYMER CHARACTERISTICS SUPPORPRODUCTS

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HARD, RIGID,HYDROPHOBIC

PMMA NIGLIGIBLE GAS PERMEABILTIY,IOW WATER CONTENT,MEDIUM WETTABILITY

WETTING SOLUTIONSOAKING SOLUTIONCLEANING SOLUTION

SOFT,FLEXIBLE,HYDROPHILIC

HEMA HIGH WATER CONENT,LOW GAS PERMIABILITY,GOOD WETTABILITY,

CLEANING SOLUTIONDISINFECTION SOLUTION

FLEXIBLE HYDROPHOBIC

SILICONE RUBBER

SILICONE VINY PYRROLIDONE

GOOD GAS PERMIABILITY,POOR WETTABILITY

WETTING SOLUTIONSOAKING SOLUTIONCLEANING SOLUTION

RIGID,HYDROPHILIC CELLULOSE ACETATE BUTYRATE

GOOD WETTABILITY WETTING SOLUTIONSOAKING SOLUTIONCLEANING SOLUTION

• ADVANTAGES• WEARER COPMFORT• EASY ADAPTIBILITY• ALLOW AN EASIER TRANSITION TO EYE GLASSES• DISADVANTAGES• REQUIRED MORE CARE• DUE TO FLEXIBILITY ACCURATE FIT TO EYE IS MORE

DIFFICULT• WEARER LIFE IS SHORTET THAN HARD ONE

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Care of contact lenses:

• Products for soft contact lenses:

Cleaners

- To remove lipid and protein debris

- formulation:

1- viscolizing surface-active agent: to enable

gentle friction with fingertips

2- antibacterial-fast acting: benzalkonium chloride

Products for soft contact lenses:

• Rinsing and storage solutions- Facilitate lens hydration, - Inactivation of microbial contamination and

prevent the lens from drying out

Products for soft contact lenses:

- Rinsing and storage solutions:- Formulation:- 0.9% Nacl (isotonic)- Antibacterial- 3% hydrogen peroxide for 30 min

followed by inactivation with sodium pyruvate.

Products for hard contact lenses:

• Rinsing and storage solutions- For cleaning, microbial inactivation and hydration

Formulation:- surface-active agent

- Antimicrobial:

(0.01% benzalkonium chloride + 0.1% sodium edetate )

Products for hard contact lenses:

Wetting solutions- To achieve rapid wetting by the lachrymal fluid and

promot comfort

- Facilitate insertion of the lens

- Provide lubrication

Products for hard contact lenses:

Buffering solutions :• Hypromellose eye drops B.P.C:

• Buffered to pH 8.4 TO 8.6 with boric acid and borax

• These solutions better tolerated by eye as more alkaline or acid preparations causes fogging effect.

Ocular inserts : OCULAR CONTROLLED DRUG DELIVERY DEVICESDefinition-

Sterile preparations, with a solid or semisolid consistencyMain objective is to increase contact time between conjunctival tissue and preparationInserted into the eye and worn under the upper or lower lidEnsures a sustained and controlled release effect

Requirements for success-

ADVANTAGES LIMITATIONS

CLASSIFICATION

The ocular implants are flexible, oval inserts which consist of a medicated core reservoir prepared out of a hydrogel type of materials.

They are classified as follows1.Insoluble inserts

Diffusion controlled ocular inserts Osmotic ocular insets Hydrophilic matrix type ocular inserts (contact lens type)

2.Soluble inserts3.Bio-erodible inserts4.Implantable silicone devices5.Implantable infusion devices

Ocufit® &Lacrisert ® Minidisk ocular therapeutic system New ophthalmic delivery systems (NODS®)

. Ocular InsertsI. Insoluble inserts:

• Insoluble insert is a multilayered structure consisting of a drug containing core surrounded on each side by a layer of copolymer membranes through which the drug diffuses at a constant rate.

• The rate of drug diffusion is controlled by:- The polymer composition- The membrane thickness- The solubility of the drug

e.g. The Ocusert® Pilo-20 and Pilo-40 Ocular system - Designed to be placed in the inferior cul-de-sac between

the sclera and the eyelid and to release pilocarpine continuously at a steady rate for 7 days for treatment of glucoma.

Insoluble ophthalmic insertsDiffusion controlled ocular insertsThese consists of a medicated core prepared out of a hydrogel polymer like alginates, sandwiched between two sheets of transparent lipophilic, rate controlling polymer.

The drug molecule penetrate through the rate controlling membranes at zero order rate process. dQ/dt = Dp Km (Cr-Ct)/δm dQ/dt = Dp Km Cs/δm (Cr >> Ct sink condition) eg ; ocusert pilo-20

Synthetic and semi- synthetic polymers-

Offer additional advantage of simple design & easily processed.Soluble synthetic polymers

Cellulose derivatives- HPC, MC, HEC, HPMC, SOD. CMCothers- poly vinyl alcohol, ethylene vinyl acetate co polymer

Additives Plasticizers- poly ethylene glycol, glycerine, propylene glycolcomplexing agent- PVPBioadhesives- poly acrylic acids, methyl hyroxy ethyl cellulose

Soluble cellulose derivative inserts are composed of 30% of water. Presence of water is unfavorable from stand point of stability of drug.

Insert can be sterilized by exposure to gamma radiation without the cellulose component being altered.

The first soluble ophthalmic drug insert (SODI) developed was of soluble co-polymer of acrylamide, N- vinyl pyrrolidone & ethyl acetate.

It was in form of sterile thin films or wafers or oval shape, weighing 15 – 16 mg.

A new type of ophthalmic insert incorporating a water- soluble bio-adhesive component in its formulation has been developed to decrease risk of expulsion & ensure prolonged residence in eye, combined with the controlled release.

These inserts, named bio-adhesive ophthalmic drug inserts (BODI)

II.Soluble Ocular inserts:

Lacrisert is a sterile ophthalmic insert use in the treatment of dryEye syndrome and is usually recommended for patients unable to obtain symptomatic relief with artifical tear solutions.

The insert is composed of 5 mg of Hydroxypropyl cellulose in a rod-shaped form about 1.27 mm diameter by about 3.5 mm long.

II.Soluble Ocular inserts:

- Soluble inserts consists of all monolytic polymeric devices that at the end of their release, the device dissolve or erode.

Typesa) Based on natural polymers e.g. collagen.

b) Based on synthetic or semi synthetic polymers e.g. Cellulose derivatives – Hydroxypropyl cellulose, methylcellulose or Polyvinyl alcohol, ethylene vinyl acetate copolymer.

- The system soften in 10-15 sec after introduction into the upper conjunctival sac, gradually dissolves within 1h , while releasing the drug.

- Advantage: Being entirely soluble so that they do not need to be removed from their site of application.

BIO ERODIBLE INSERTS

Main component of this type of inserts is the bio-erodible polymers.

They undergoes hydrolysis of chemical bonds & hence dissolution.

Bio-erodible matrix controlling the release rate of the drug ensures zero order release rate.

Eg., poly (ortho esters), poly (ortho carbonates)

Great advantage of these bio-erodible polymers is the possibility of modulating their erosion rate by modifying their final structure during synthesis.

Implantable silicone devices

Developed for the local delivery of an anti-neoplastic drug to the intra-ocular site.

Composed of 2 sheets of silicone rubber glued to the edge with adhesive to form a balloon like sac through which a silicone tubing (0.3 mm dia) is inserted.

Such devices have significant potential for local controlled delivery of anti- bacterial, anti-cancer, & anti-viral drugs to anterior chamber of eye.

Other delivery devices

Ocufit® is a sustained release rod shape device made up of silicone elastomer.

Lacrisert® is another cylindrical device, which is made of HPC and used for treating dry- eye patients.

Mini disk ocular therapeutic systems (OTS)- It is a miniature contact lens shaped, made of silicone based pre polymer. It requires less time & less manual dexterity for insertion, when compared with lacrisert®.

New ophthalmic delivery system (NODS)- It is a method for delivering precise amounts of drugs to eye within a water soluble, drug- loaded film.When evaluated in humans, the NODS produced an 8 fold increase in BA for pilocarpine with respect to std. eye drop formulations.

Preparation of ocular insertCasting method

Characterization of inserts

Uniformities of weight & thickness

Uniformities of drug content

Surface PH

In-vitro release studies (continuous flow through apparatus)

Ocular irritation test

In-vitro microbial studies

PACKAGING

Ophthalmic insert 5 mg supplied in packages of 60 sterile unit dosage forms.

Each wrapped in an aluminum blister.

With two reusable applicators.

A plastic storage container to store the applicators for use.

How To Use •To apply the system, wash hands first. •Tilt your head back, gaze upward and pull down the lower eyelid to make a pouch. •Place the system into the pouch. •Blink a few times and roll your eye to move the insert into place. •Practice inserting and removing the system in the doctor s office where you can be shown the proper technique. •Damaged or deformed systems should not be used or kept in the eye. •Replace with a new system.

Advances in ocular drug deliveryAdvances in ocular drug delivery

11. Ophthalmic gel for pilocarpine. Ophthalmic gel for pilocarpine

Poloxamer 407 (low viscosity, optical clarity, mucomimetic property)

2. Ophthalmic prodrug2. Ophthalmic prodrugDipivalyl epinephrine (Dipivefrin)

Lipophilic increase in corneal absorptionEsterase within cornea and aqueous humor

3. Continuous delivery system based upon the osmotic property3. Continuous delivery system based upon the osmotic propertyThin flat layer, contoured three-dimensional unit

Conform to the space of the upper cul-de-sacDelivery of diethyl carbamazine in ocular onchocerciasis

4. Gel delivery system4. Gel delivery system

Biodegradable polyisobutyl-cyano acrylate (PIBCA) colloidal particulate system of pilocarpine to incorporate it

into a Pluronic F127 (PF 127)-based gel delivery system.

5. Mucoadhesive Polymer.Mucoadhesive polymer, the tamarind seed polysaccharide,

as a delivery system for the ocular administration of hydrophilic and hydrophobic antibiotics.

THANK U…

“ Sight is the sense which is more valuable than all the rest”

So Take Care Of Eyes!!!!!!