UNIT 3: Ophthalmic Preparations

What is the most common topical ophthalmic preparation?

Ophthalmic Solutions

How much fluid can the conjunctival sac accomodate without spilling?

20 mcl to 30 mcl

What is one way to maximize local absorption of an ophthalmic solution?

punctual occlusion

How do ophthalmic suspensions prolong drug release?

particles are retained in the conjunctival sac which allows them to slowly go into solution and therefore increases contact time

How does a large particle size in ophthalmic suspensions increase the risk of the drug being washed out?

cause irritation which results in tears

Which particle size is not allowed in ophthalmic suspensions?

90 mcm

What particle size can be most prevalent in ophthalmic suspensions?

25 mcm

Why is it important to ensure particles are readily dispersible in an ophthalmic suspension?

ensure uniform dose administration

What type of changes can occur to ophthalmic suspensions during storage that change drug solubility and dissolution?

polymorphic

Why can't we resolve the issue of cake formation with addition of a flocculating agent in ophthalmic suspensions?

large floccules irritate the eye

How do we resolve the issue of cake formation in ophthalmic preparations?

suspending agents (polymer solution)

What are 3 advantages of ophthalmic emulsions?

1. prolong drug release

2. higher drug concentrations in cornea

3. delivering highly lipophilic drugs

How can the use of an emulsion prolong drug release rate?

O/W diffusion mechanism

What type of emulsion is used for solubilizing Ciclosporin?

O/W submicron emulsion

Which type of ophthalmic preparation can increase the stability of hydrolysable compounds?

Hydrophobic Ointments (oleaginous)

What are 2 advantages of ophthalmic ointments?

1. reducing drainage

2. entrapment in conjuctival sac

Why do ophthalmic ointments have a more sustained release rate than suspensions or solutions?

ointments can be entrapped in the conjuctival sac and the drug must leave the base and enter into solution

What are 3 disadvantages of ophthalmic ointments?

1. difficult to administer (variable doses)

2. vision blurring

3. potential entrapment of drug in base

In an ophthalmic ointment, what occurs when the hydrophobic drug has too great of an affinity for the base?

inhibiting drug release

When is it best to apply ophthalmic ointments?

night-time

What type of base does an ophthalmic gel utilize?

Water-Soluble Bases

What are 2 advantage of In Situ ophthalmic gels?

1. dose uniformity

2. easy administration

What are 3 things that trigger a phase transition in ophthalmic gels?

1. body temperature

2. ions

3. pH

How does charge related to the physical state of In Situ gels?

When in the liquid form, the polymers are ionized and interact with water but when they become unionized by reaction with the trigger the polymers are in the "solid" state

Where does the In Situ gel form the viscoelastic gel at?

conjunctival sac

What pH range can the eye tolerate?

3.5 to 9

What do we typically want the pH of ophthalmic preparations to be?

as close as possible to 7.4

What is the range of isotonicity limits that does not produce discomfort in the eye?

0.6% to 2%

Which surfactant type is the least irritating?

Nonionic

What is the use of surfactants in ophthalmic preparations?

solubilize/disperse drugs

What are 3 examples of nonionic surfactants commonly used in ophthalmic preparations?

1. polysorbate 20

2. polyoxyl 40 stearate

3. polyoxypropylene-polyoxyethylenediol

What is the zero shear viscosity value for normal tears?

6.4 mPa

What is the acceptable viscosity for ophthalmic preparations?

up to 15 mPa

For ophthalmic solutions with a viscosity >>15mPa, what occurs?

increased lacrimation/drainage in order to restore tear film to physiological viscosity

What is added to ophthalmic preparations in order to reduce drainage rate?

Water-Soluble Polymers (viscosity enhancers)

What are 6 examples of Water-Soluble Polymers that are used to increase viscosity of ophthalmic solutions?

1. Poly (vinyl alcohol) (PVA)

2. Polyvinylpyrrolidone

3. Methylcellulose

4. Hydroxypropyl methylcellulose

5. Carboxymethylcellulose

6. Polyethylene glycol (PEG)

What effect does an increase in viscosity of ophthalmic solution have on absorption?

increased absorption by prolonging drug retention

What type of container is preferred for ophthalmic preparations?

fixed-dropper containers

What are 2 reasons that fixed-droppers are the preferred container for ophthalmic preparations?

1. administration ease

2. less likely to acquire airborne contaminants

What are the 2 methods of sterilization for ophthalmic solutions/suspensions?

1. autoclaving

2. bacterial filtration

What type of sterilization technique do we use for formulations that are thermodynamically unstable?

bacterial filtration

Which of the sterilizing techniques is better at killing microbes?

autoclaving

Which of the sterilizing techniques is capable of removing ALL tiny particles?

bacterial filtration

What are the conditions for autoclaving?

1. 121 C (250 F)

2. 15 minutes

How are preservative free ophthalmic formulations typically packaged?

single-dose containers

What is added to ophthalmic preparations in order to MAINTAIN sterility throughout patient use?

antimicrobial preservatives

What are 6 examples of antimicrobial preservatives used in ophthalmic preparations (solutions/suspensions)?

1. Benzalkonium chloride (BAC)

2. Benzethonium chloride

3. Chlorobutanol

4. Phenylmercuric acetate

5. Phenylmercuric nitrite

6. Thimerosal

What type of sterilization technique do we use for preservatives such as Cholorbutanol?

bacterial filtration

What are 2 effects of Cholorbutanol decomposition to Hydrochloric Acid in even moderate heat?

1. increases risk of susceptible growth

2. alter pH, affecting ionization

What is the issue with ophthalmic preparations using drugs that have COOH groups (hydrophilic)?

low corneal permeation

How do we enhance corneal permeability through the use of prodrugs?

esterification optimizes lipophilicity of the drug

How does the prodrug become converted to the parent drug in the cornea?

hydrolysis by esterases

What is the prodrug for latanoprost acid?

latanoprost

What is the prodrug for travoprost acid?

travoprost

Which form of the drug has an ester?

prodrug

What are 2 ways that formation of prodrugs are advantageous?

1. increased corneal permeability

2. avoid systemic absorption

How can we avoid systemic absorption?

reducing polarity of the drug

Why do we have to form a prodrug for Adrenaline (polar)?

it has rapid celarance from the ocular surface via nasal lacrimal drainage = increased systemic absorption = severe side effect

What is the prodrug for Adrenaline?

Dipivalyl Adrenaline (Dipivefrine)