Eye and Opthalmic Dosage Forms

eye

is a specialized sensory organ that detects light and converts it into electrical signals, which is interpreted by the brain to create vision

anterior and posterior

What are the 2 segments of the eye?

6

There are _____ extraocular muscles that help move the eyeballs within the orbit.

optic nerve

-bundle of fibers that connect the retina with the brain

-enables sight

cornea

Clear (transparent) dome that covers the eye

lens

Translucent-packed protein that focuses light rays onto the retina

iris

Thin, colored, circular structure made of connective tissue and the muscle that controls the size of the pupil

ciliary body

Aqueous humor production

posterior segment or chamber parts of the eye

-sclera

-choroid

-retina

-optic nerve

-artery and veins

-vitreous humor

sclera

Visible white portion that provides shape and resistance

choroid

-Pigmented layer of connective tissue and blood vessels

-Provides oxygen and nutrients to the eye

retina

-Light-detecting component consisting of photoreceptors

-Creates impulses that are sent through the optic nerve to the

brain

artery and veins

carry blood to and from the eye

vitreous humor

-Hydrogel matrix tissue, ~4.5 ml

-Convective circulation with little stirring

-Becomes more fluid with advancing age

keratitis

inflammation of cornea

iritis

inflammation or iris

conjunctivitis

inflammation of the conjunctiva

glaucoma

increased intraocular pressure

dry eye disease

tear film disruption

blepharitis

inflammation of the eyelids

posterior segment ocular diseases

Uveitis

Retinitis

Endophthalmitis

Diabetic retinopathy

Age-related macular

degeneration

Choroidal neovascularization

Retinoblastoma

Retinal degeneration

Retinal detachment

routes of admin and dosage forms for the eye

-intravitreal

-intracameral

-topical

-suprachoroidal

-periocular

-systemic

dynamic barriers for topical administration

Tear overflow and blinking rate

Protein binding

Enzymatic degradations

Nasolacrimal drainage

Static barriers to topical admin

Cornea

Conjunctiva

Sclera

Blood-Aqueous Barrier / Blood-Retinal Barrier

< 5 % of the drug reaches the target tissues due to tear drainage, blinking, and limited corneal permeability (pre-corneal barriers)

What is the issue with low bioavailability with topical admin?

bc they are quickly washed away by tears and blinking, requiring drug penetration

Why is there a short retention time with topic admin for the eyes?

poor

Frequent dosing or invasive procedures can lead to ________ adherence to treatment regimens.

permeation enhancers

-temporarily disrupt the corneal epithelium

-EX: surfactants, cyclodextrins

nanotechnology

encapsulate the drug, improving stability and penetration

prodrugs

-chemically modified to enhance lipophilicity

-EX: Latanoprost, valacyclovir,

mucoadhesive systems

increase contact time to the cornea

Challenges with the Systemic route

❖Oral bioavailability

❖Hepatic metabolism

❖Protein binding

❖Blood ocular barriers

❖Targeting a specific area

❖Side effects

Ophthalmic Dosage Forms

-eyedrops

-ointments

-inserts

-drug eluting contact lens

-implants

-oral administration

eyedrops

-solutions

-suspensions

-gels/gel forming

-emulsions

-nanosystems (liposomes, polymeric/lipid particles)

eyedrops

What is the most common ophthalmic dosage form?

❖Treat infection

❖Dilate or contract pupil

❖ Relieve pain, itching, discomfort

❖Lubricate eyes

❖ Administer medication before examination/surgery

What is the purpose of topical eyedrops?

eye drops

are sterile solutions, suspensions, or emulsions intended for instillation in the eye

right eye (ocular dexter)

OD

left eye (Ocular sinister)

OS

both eyes (Ocular uterque)

OU

eye drop solutions

dissolution of the active ingredient and/or a portion of the excipients into water

advantages of eye drop solutions

• Drug is in solution and ready for absorption

• Easy instillation

• Rapid relief

• Localized treatment

• Dose uniformity

drawbacks to eye drop solutions

• A drug has to have the required solubility

• Rapidly cleared from the ocular surface

• Preservatives

• Patient compliance issues if multiple applications needed

eye drop suspensions

a finely divided solid is dispersed uniformly in a liquid dispersion medium

advantages to eye drop suspensions

• Formulation approach for poorly soluble compounds

• Zero-order release

• Longer retention in the cul-de-sac compared to solutions

• Prolonged exposure

• May provide greater stability for compounds undergoing hydrolysis

drawbacks to eye drop suspensions

• May cause irritation

• Foreign particle sensation can lead to greater tear flow and irritation

• Lower bioavailability

• Chance of dose variation

eye drop gels

Composed of mucoadhesive polymers that provide localized delivery of an API to the eye

advantages to eye drop gels

• Prolonged drug retention

• Improved bioavailability

• Reduced side effects

• Convenience

drawbacks to eye drop gels

• Blurred vision

• Irritation

• Drug release challenges

• Storage issues

• Limited patient compliance

eye drop emulsions

Dissolving or dispersing the API into an oil phase, adding suitable emulsifying and suspending agents, and mixing with water vigorously to form a uniform O/W emulsion

advantages to eye drop emulsions

• Better for lipophilic molecules allowing higher dosing

• Longer retention on the ocular surface

• Provides greater stability for compounds undergoing hydrolysis

• Better ocular bioavailability

drawbacks to eye drop emulsions

• Formulation challenges

• Toxicity of surfactant systems needed to stabilize

• May cause increased systemic exposure compared to solutions or suspensions

• Compatibility issues

less

The more complicated the dosage form, the _______ drugs available in that form.

0.9% solution of sodium chloride

Body fluids, including blood and tears, have an osmotic pressure corresponding to that of a:

250-350 mOsm

The ocular tissues can tolerate a tonicity range of ___________. Sometimes higher osmolarity is used to increase transcorneal permeation

NaCl

KCl

Glycerin

Propylene glycol

What are the commonly used tonicity adjusting agents?

• for greater comfort to the eye

• to render the formulation more stable,

• to enhance the aqueous solubility of the drug,

• to enhance the drug's bioavailability to maximize preservative efficacy

The pH of an ophthalmic preparation may be adjusted and buffered for one or more of the following purposes:

-citrates

-borates

-phosphates

-acetates

What are the common buffering agents?

• acts as a suspending agent

• acts as a stabilizer

• increases retention on the ocular surface

In the preparation of ophthalmic solutions, a suitable grade of a viscosity enhancer is frequently added to:

• methylcellulose of 4,000 cP at 0.25% and the 25-cP type at 1% concentration

• Hydroxypropyl methylcellulose (HPMC)

• Polyvinyl alcohol (PVA)

• Polyvinylpyrrolidone (PVP)

What are the commonly used viscosity enhancers?

30 microliters

How much can the cul-de-sac hold in a non-blinking state?

10 microliters

How much can the cul-de-sac hold in a blinking state?

50 microliters

A single drop of an ophthalmic solution or suspension measures about _________ so much of an administered drop may be lost.

Antioxidants

sodium metabisulfite, sodium sulfite, Ascorbic acid

Solubilizers

surfactants (e.g. Tween®, Cremophor®), cyclodextrins, polymers

Stabilizers

chelating agents (e.g. EDTA), complexation agents (e.g. cylcodextrins)

Preservatives

benzalkonium chloride, 0.004% to 0.01%; Polyquad, Benzethonium chloride, 0.01%

Permeation Enhancers

surfactants, benzalkonium chloride, cyclodextrins

0.22 micrometer

Topical eyedrops must pass through a ______ filter.

no

Is sterile filtration suitable for suspension?

terminal sterilazation

-autoclave at 121°C (250°F) for 15 minutes most commonly

used

-Not suitable for heat labile drugs and plastic containers

-sterile filtration

-terminal sterilization

-aseptic manufacturing

-gamma rays

What are the types of sterilization for topical eyedrops?

must be

Ophthalmic solutions, suspensions, and emulsions _________ sterilized for safe use.

-use of mucoadhesive agents

-smart polymer

What are the approaches to increase retention on ocular surface?

smart polymer

sol-gel transition induced by temperature, ions, pH or combo of factors

ointments

API dissolved, suspended, or emulsified in an ointment base

advantages of ointments

• Prolonged contact time with the ocular surface

• Flexibility in drug choice

• Improved drug stability

drawbacks of ointments

• Sticking of eyelids

• Blurred vision

• Poor patient compliance

• Matting of eyelids

other approaches for sustained release

❖Extend the release of drugs in ocular fluids and tissues particularly in the posterior segment by delivering a sustained release of drugs to the site of action

❖Very small, primarily injected (25 gage needle is optimal)

❖Biodegradable

❖Nonbiodegradable

biodegradeable

❖Delivers drug through bulk erosion of polymer

❖zero-order kinetics, 3-6 months delivery

nonbiodegradable

❖Fluid in eye dissolves and elutes drug from matrix

❖Very long lasting, 12 months+ delivery

Dextena

-releases for 30 days

-intracanalicul implant

Durysta

-4 to 5 months to dissolve

-intracameral implant

advantages to intravitreal injections

Direct application bypassing all physiological barriers, enhanced efficacy

disadvantages to intravitreal injections

chances of infection and retinal detachment, a physician procedure, frequent injections, cost

advantages of periocular injections

Bypasses some of the barriers, localized treatment, less invasive, prolonged effect, improved tolerance

disadvantages of periocular injections

some of the barriers still exists, loss in the orbital cavity, chances of infection, physician procedure, variable drug absorption

Intravitreal Implants

❖Ozurdex

❖Retisert

❖Vitrasert

Sterile dosage forms

❖Filtration (0.22 um filter), terminal sterilization (autoclave), aseptic manufacturing

❖Essentially free from foreign particles

❖Produced in a highly controlled environment

❖Must be sterile in a final container and remain sterile during shelf life and while in use

specialized dosage forms

Ophthalmic inserts, medicated contacts, implants

soft plastic containers with a fixed built-in dropper

How are most ophthalmic products packaged?

2, 2.5, 5, 10, 15, and 30 mL

What are the sizes of most ophthalmic solutions and suspensions?

eye cup which should be cleaned and dried thoroughly before and after each use

How are ophthalmic solutions that are used as eyewashes generally packaged?

color coded

Bottle caps are __________ according to the therapeutic class of the product.

tan

Anti-infective

pink

Anti-inflammatory/steriods

red

mydriatics and cycloplegics

gray

non-steroidal anti-inflammatories

green

miotics

yellow

beta-blockers