Pharmaceutics II Exam IIII: Ophthalmic Drug Delivery Formulations

What is the most common type of ophthalmic dosage form?

Ocular solutions

Ocular solutions are designed for local action in the _______ segment

anterior

What are 3 benefits of ophthalmic solutions?

-Ease of manufacture

-Rapid onset

-Patient compliance

What are 3 challenges of ophthalmic solutions?

-Short residence time (1-2 min)

-Blinking and tear drainage (drug loss)

-Corneal barriers limit bioavailability (1-5%)

What are the ideal properties of a ophthalmic solution?

• Sterile• Isotonic

• pH-compatible with tears (7.4)

• Generally tolerate pH in the range of 6.5 to 8.5

• Non-irritating

• Preserved (if multi-dose)

• Stable (physically and chemically)

What are the key formulation components of an ophthalmic solution?

-API

-Vehicle (water, glycerol, PEG)

-Buffers (phosphate, citrate, acetate, tris, histidine)

-Tonicity adjuster• Glycerol, PEG

-NaCl, KCl, boric acid• Dextrose, mannitol, sorbitol

-Preservatives

-Antioxidant (if needed)

Why is Boric acid a preferred tonicity adjuster?

it is a:

-pH buffer

-Preservative

-Isotonicity adjuster

API must be __________

water soluble

T/F API must be water-insoluble

False, water soluble

API are often formulated as ________ (timolol maleate)

salt forms

API must be stable at ___________ pH or ______ pH

phyiological, modified

API include:

-Anti-infectives (Antibiotics &Antivirals)

-Anti-inflammatory

-Anti-glaucoma

-Artificial tear/lubricants

-Anti-histamines

-Immunomodulators

What is the difference in antibiotics and antivirals?

Antibiotics are lower dose and increased selectivity

An ophthalmic vehicle must be up to the USP standard for __________

water for injection

The USP water for injection includes:

-Sterile

-Pyrogen-free (low endotoxin levels)

-No particulate matter

T/F ophthalmic vehicles must be sterile and pyrogen-free free but can have particulate matter

false, no particulate matter

T/F Ophthalmic vehicles must be sterile

true

_____ act as a solvent and carrier for drug and excipients

Vehicle

Once a ophthalmic solution is prepared it is _____

sterlized

What are the 3 ways ophthalmic solutions are sterlized?

-Autoclaving

-Filtration through 0.22 um filter

-Aseptic filtration/handling

Ophthalmic solutions are prepared by filtration through ____ filter

0.22 um

ophthalmic buffers maintain pH _________

6.5-8.5

What pH range does the eye tolerate?

6.5-8.5

Examples of O. buffers

Phosphate, borate, citrate

What is a challenge for O. buffers?

Balancing drug solubility vs comfort

Examples of Tonicity adjusters:

-NaCl

-KCl

-Dextrose

-Glycerol

-PEG

-Boric acid

What is the most common preservative?

Benzalkonium chloride (BAK)

T/F O. Solutions must have preservatives

True

Most ophthalmic packaging must be which 2 things?

Sterile and preservative free

What type of O. packaging minimizes risk of irritation or preservative-related toxicity?

One time use

Single use ophthalmic packaging allows solutions to be ______ and _____ free

sterile and preservative

An ocular suspension is a sterile, liquid preparation containing solid particles of a ________ soluble drug dispersed in an aqueous vehicle

poorly

Suspensions allow (higher/lower) drug loading?

higher

_______ are often used for anti-inflammatory, antifungal, or antibiotic eye medications

Ophthalmic suspensions

Why are suspensions formulated the way they are?

Because some drugs have low water solubility

What an example of a drug with low water solubility?

Corticosteroids- prednisolone acetate

What is the particle size for an O. suspension?

<10 um

What is the preferred range for an O. suspension?

1-5 um

Why is the particle size important for O. suspension?

Small particle size avoids gritty sensation and corneal irritation

How is particle size reduced for O. suspension?

jet milling or micronization

Can O. suspensions be terminally sterilized?

No solid particles will aggregate and settle

How are O. suspensions be sterilized?

They must be manufactured under aseptic conditions and sterilized by filtration

What often causes eye irritation in o. suspensions?

Surfactants

How can sterilized suspension formulations be made?

The powder can be sterilized with:

-Aseptic technique

-y radiation

-Ethyl oxide

Examples of O. suspensions:

-Prednisolone acetate

-Polyvinyl alcohol

-Polysorbate 80

-Sodium chloride

-Disodium phosphate

-Benzalkonium chloride

-Water

_______ sterile semisolid preparation for the application to the conjunctival sac

Ointment

Ointment is applied to the ________

conjunctival sac

Ointment is used to (increase/decrease) drug contact time with the eye

increase

When is ointment typically applied?

at night because it causes blurred vision

Ointment _____ and _______ the ocular surface (especially post-surgery)

protects, lubricates

Common ointment bases include:

-mineral oil (liquid) + white petrolatum (semi-solid)

-Lanolin

Can ointment be sterilized by filtration?

no

T/F Ointment can be sterilized by filtration

false, cannot

How is ointment sterilized?

-Aseptically

-gamma radiation

-heat

What should be avoided when sterilizing ointment?

Heat because it can destabilize the base

Ocular gels: pre-formed _____, ______ bases

semisolid, hydrophilic

In situ gelling systems: ______ upon instillation, ____ in the gel due to environmental triggers

liquid, gel

What is the advantage of gels/in-situ gelling systems?

The delivery the convenience of drops with prolonged action like ointments

What are triggers for in-situ gelation?

body temperature, tear ions, tear pH

What are the types of in-situ gelations?

-Thermosensitive

-Ion sensitive

-pH sensitive

O. Emulsions are usually ____/_____

o/w (oil in water)

Emulsions are suitable for poorly _____ drugs (cyclosporine, corticosteroids)

water-soluble

O. Emulsions are _____ corneal penetration

enhance

What is the preferred droplet size for O. emulsions?

<200 nm for clarity and better bioavailability

T/F zeta potential affects emulsion stability

True

Emulsion is inherently thermodynamically (stable/unstable) - must pass stability testing (creaming, phase separation)

unstable

How are O. emulsions sterilized?

aseptic handling, filtration for aqueous phase, heat for oil phase

O. emulsions sterility: aseptic handling, ________ for aqueous phase, _____ for oil phase

filtration, heat

______: Solid or semisolid sterile preparations designed to be placed in the conjunctival sac

ocular inserts

Ocular inserts, solid or semisolid sterile preparations designed to be placed in the _________-

conjunctival sac

Ocular inserts can be biodegradable or non-biodegradable (but must be _________)

biocompatible

Ocular inserts provide ________/_______ release over hours to days

controlled/sustained

How do ocular inserts reduce side effects?

lower amount of drug release

Ocular inserts are good for chronic conditions such as:

-Glaucoma

-Dry eye

-Post-surgery inflammation

Ocusert: ________ 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 ______ rate

insoluble, constant

The rate of drug diffusion is controlled by with ocular inserts:

- The polymer composition

- The membrane thickness

- The solubility of the drug

The Ocusert therapeutic system is a flat, flexible, elliptical device designed to be placed in the _________ between the sclera and the eyelid and to release Pilocarpine continuously at a steady rate for 7 days.

inferior cul-de-sac

3 layers of ocular inserts:

1. Outer layer: Ethylene vinyl acetate copolymer layer. (Rate Controlling Membrane)

2. Inner Core - Pilocarpine gelled with alginate main polymer

3. A retaining ring - of EVA and with titanium dioxide

T/F contact lenses can be pre-soaked in drug solutions

true

Drug incorporation of contact lenses depends on whether their structure is ________ or _____

hydrophobic/hydrophilic

The drug release with contact lenses depends on:

• Amount of drug

• Soaking time

• Drug concentration

_____ inserts: solid inserts absorb the aqueous tear fluid and gradually erode or disintegrate

Erodible

Erodible inserts the drug is _____ leached from the hydrophilic matrix

slowly

Erodible inserts quickly lose their ___________ and are squeezed out of the eye with eye movement and blinking

solid integrity

T/F Erodible inserts have to be removed at the end of their use

False, they do not need to be removed

Frontiers of pharmaceutical science for ophthalmic:

Nanoparticles/micelles/liposomes