W1C - Ophthalmic drug formulation and delivery

Question 1

What is pharmacokinetics?

Answer 1

Study of the time course of absorption, distribution, metabolism and elimination of a drug

Question 2

What does drug delivery focus on?

Answer 2

Mainly drug absorption and distribution

Question 3

What factors influence ocular drug absorption?

Answer 3

Molecular properties of the drug, viscosity of the vehicle, functional status of the tissue

Question 4

Define bioavailability in the context of ocular drug delivery.

Answer 4

Compartment (theory) = region of tissue or fluid through which a drug can equilibrate and diffuse with relative freedom

Question 5

What are prodrugs?

Answer 5

Inactive drugs that are converted to an active form after tissue penetration

Question 6

Give examples of prodrugs used in ophthalmology.

Answer 6

• Latanoprost
• Travoprost

Question 7

What is the most common route of administration for ocular drugs?

Answer 7

Topical in the form of eyedrops

Question 8

What is the intra-ocular bioavailability of topically administered medications?

Answer 8

Typically less than 5% and often less than 1%

Question 9

List barriers to ocular drug delivery.

Answer 9

• Blood-aqueous barrier (BAB)
• Blood-retinal barrier (BRB)
• Endothelial pump
• Iris vascular endothelium
• Lens epithelium

Question 10

What is the role of the cornea in drug delivery?

Answer 10

Part lipophilic & hydrophilic, major functional barrier to ocular penetration

Question 11

What are some methods of ocular drug delivery?

Answer 11

• Eye drops
• Scleral plug
• Subconjunctival implant
• Intravitreal injection

Question 12

What is the double DOT technique?

Answer 12

Used for drugs with major systemic side-effects to minimize drug entry to the nasolacrimal passage

Question 13

What is the significance of tear turnover in drug absorption?

Answer 13

Limits the contact time of topically applied eye drops, clearing drugs within 5-6 minutes

Question 14

What does the term ‘ocular bioavailability’ refer to?

Answer 14

Amount of drug present at the desired effect site in the tissue where treatment is needed

Question 15

Fill in the blank: The cornea has a thickness of approximately _______.

Answer 15

500 um

Question 16

What are the four main types of preservatives used in ocular preparations?

Answer 16

• Surfactants
• Chemical preservatives
• Alcohols
• Mercurials

Question 17

What is the effect of preservatives on ocular surface?

Answer 17

Can irritate and damage ocular surface since they are formulated to kill bacteria

Question 18

What is the purpose of using iontophoresis in drug delivery?

Answer 18

To increase tissue permeability

Question 19

True or False: Most ophthalmic drugs are formulated as suspensions.

Answer 19

False (most are formulated as solutions)

Question 20

What is the role of the ciliary body (CB) in drug delivery?

Answer 20

Major role in drug removal from the eye, contains drug-metabolizing enzymes

Question 21

What is the advantage of periocular injections?

Answer 21

Can deliver high concentrations with smaller quantities of drugs to deeper ocular structures

Question 22

What is a common issue with topical administration of ocular drugs?

Answer 22

Spillage occurs due to normal tear volume being approximately 7 ul

Question 23

What happens to drugs that pass through the lacrimal sac?

Answer 23

They are variably absorbed and avoid first-pass metabolism

Question 24

What is the significance of the corneal epithelium in drug absorption?

Answer 24

It has tight junctions that stop penetration of hydrophilic drugs and large molecules

Question 25

Fill in the blank: The tear pH is approximately _______.

Answer 25

7.4

Question 26

What is the effect of increasing drop volume during drug instillation?

Answer 26

Leads to higher systemic absorption, not increased drug penetration

Question 27

What is an example of a drug that is a prodrug and has enhanced ocular penetration?

Answer 27

Dipivefrine, the ester prodrug of epinephrine

Question 28

What is the impact of preservatives on drug formulations?

Answer 28

Aim to prevent bacterial growth but can irritate ocular surfaces

Question 29

What is the purpose of using surfactants in ocular preparations?

Answer 29

They disrupt the plasma membrane of bacteria and other cells

Question 30

What type of substances do BAK (benzalkonium chloride) and chlorhexidine represent?

Answer 30

Ionically charged substances ## Footnote They kill bacteria and other cells by disrupting the plasma membrane.

Question 31

Which preservative is thought to have less effect on corneal permeability and tear film integrity?

Answer 31

Chlorhexidine

Question 32

What are the advantages of using chlorhexidine over BAK?

Answer 32

Great stability, good antimicrobial properties, and long shelf life

Question 33

What are mercurials, and give an example?

Answer 33

Chemical preservatives, e.g. thimerosal ## Footnote They can lead to sensitive issues.

Question 34

What is the action of oxidative preservatives like hydrogen peroxide?

Answer 34

Penetrate the cell membrane and interfere with cell function

Question 35

What are 'vanishing' preservatives, and name two examples?

Answer 35

Newer oxidative preservatives * Purite * Sodium perborate

Question 36

What happens to sodium perborate once it enters the eye?

Answer 36

Converted to hydrogen peroxide, then oxygen and water

Question 37

What is the purpose of unit dose dispensers in ophthalmic therapy?

Answer 37

Allow repeated administration without risks associated with preserved solutions

Question 38

What are common types of drugs available in unit dose formulations?

Answer 38

* Ocular lubricants (e.g. Systane Ultra) * Antibiotics (e.g. Chloramphenicol) * Anti-histamines (e.g. Zaditen) * Corticosteroids (e.g. prednisolone sodium phosphate) * Dilating drops (e.g. tropicamide)

Question 39

What are excipients in medications?

Answer 39

Things other than the active ingredients and preservatives

Question 40

What role do buffers play in ophthalmic formulations?

Answer 40

Maintain pH close to normal (7.4 for the eye) and adjust osmolarity

Question 41

What are tonicity agents used for in ophthalmic solutions?

Answer 41

Maintain osmolarity (290 mOsm = 0.9% saline)

Question 42

Fill in the blank: Increasing solution viscosity prolongs the ocular _______ time of drugs.

Answer 42

residence

Question 43

What are polymeric gel-forming systems?

Answer 43

Large molecules that can be preformed gels or in-situ forming gels

Question 44

What is an example of a preformed gel in ophthalmic formulations?

Answer 44

Timoptic-XE

Question 45

What is the primary formulation of ophthalmic ointments?

Answer 45

Mixture of white petroleum, liquid mineral oil, and water-miscible agents

Question 46

What is the primary disadvantage of using ophthalmic ointments?

Answer 46

Transient blurry vision and difficult administration

Question 47

What are colloidal systems used for in ophthalmic drug delivery?

Answer 47

Increase pre-ocular retention time and drug bioavailability

Question 48

What are liposomes in the context of drug delivery systems?

Answer 48

Spherical microscopic vesicles composed of concentric lipid bilayers

Question 49

What is the purpose of solid delivery systems in ophthalmology?

Answer 49

Overcome disadvantages of other topical means of administration

Question 50

What is the commercial drug release system called that was used for pilocarpine?

Answer 50

Ocusert

Question 51

What is drug compounding?

Answer 51

Preparation and supply of a single unit of a product for immediate use by a specific consumer

Question 52

What are some indications for drug compounding?

Answer 52

* Different formulation required * Sensitivity/allergy to excipients * Discontinued medicine * Different dose or concentration required * Compliance problems

Question 53

What is the importance of clear instructions for compounding?

Answer 53

To avoid prescribing the wrong percentage or dose