Nasal, Otic and Ocular Drug Delivery

Question 1

Local vs. systemic

Answer 1

• Local
– Delivery to the site of action
• Systemic
– Delivery via a particular site to another part of the
body

Question 2

Ophthalmic Drugs:

Answer 2

The drugs that are used for the diagnosis & treatment of ocular diseases are usually known as ophthalmic drugs.

Question 3

Various available ophthalmic products are

Answer 3

• Eye drops
• Eye lotions
• Eye suspensions
• Eye ointments
• Contact lens solutions
• Ophthalmic inserts

Question 4

Ocular drug delivery

Answer 4

• Predominately local drug delivery

* Eye is not really a significant portal for systemic drug delivery

Question 5

• Systemic conditions

Answer 5

– May arise from diabetes, hypertension etc

– Consider systemic absorption as toxicity?

Question 6

• Local conditions

Answer 6

– E.g. glaucoma, cataract, macular degeneration

Question 7

Ocular drug delivery

• Advantages

Answer 7

– Reduce systemic effects

– Reduce required dosage

Question 8

Ocular drug delivery

• Disadvantages

Answer 8

– Patient compliance

– Sensitivity of the eye to the application of medicines

Question 9

Structure and Physiology

Answer 9

Cornea is main pathway from
diffusion of drugs in to eye0.5 – 0.7mm thick
5 layers.

Stratified epithelium

Highly vascularised
External surface coating
Contains a viscous vitreous media
Size, therefore size / volume of applied dose.

Question 10

Routes of ocular del

Answer 10

For example:
- An intravitreal delivery is normally facilitated by a injection, normally a solution (due to possible obscuration, but see later slides) into the vitreous humour of the eye, between the lens and the retina.
- A sub-Tenon’s injection of, for example, a local anaesthetic near or beyond the equator is performed using a cannula, which has been inserted under the conjunctiva and Tenon’s capsule a few millimetres from the limbus and is slid posteriorly to produce anaesthesia of the globe as well as paralysis of the extraocular muscles. A sub-Tenon’s injection may also be used to
administer medication (e.g. corticosteroids) in posterior segment inflammation.

Question 11

Subconjunctival injections

Answer 11

• Generally used to deliver anti-infective drugs or
corticosteroids for conditions not responding to topical therapy
• Drug diffuses to anterior and posterior chambers and vitreous humour
• Low volume only (1ml)
– Repeated injections?

Question 12

Ophthalmic Drug Delivery System

Answer 12

draw

General routes of drug delivery:
Lacrimal gland
Ocular delivery
Lacrimal fluid
Precorneal cavity Corneal epithelium Metabolism
Conjunctival uptake Endothelium/ Stroma
Lacrimal canals Aqueous humor Elimination
Lacrimal sacs
Nasolacrimal duct
Nasal canal Systemic circulation & elimination, etc.

Question 13

Common disorders of the eye

Answer 13

• Astigmatism
• Glaucoma
• Myopia
• Retinitis pigmentosa
• Blurred vision
• Hyperopia
• Blepharitis
• Corneal ulcer
• Photokeratitis
• Cataracts

Question 14

Diseases of the Eye - Glaucoma

Answer 14

• Describes a group of disorders characterised by a loss of visual field associated with cupping of the optic disc and with optic nerve damage
– Acute-angle glaucoma (acute-angle closure glaucoma) occurs when the outflow of aqueous humour from the eye is obstructed by bowing of the iris against the trabecular meshwork

Question 15

Intra-ocular devices

Answer 15

• Intraocular devices have been developed as they:
– release the drug at a steady rate
– allow accurate dosing
– release drug over long period of time (potentially, up to several months)
– reduction in systemic absorption
– show an increase in patient compliance

Question 16

Intra-ocular devices disadv

Answer 16

– there may be a surgical requirement to remove the implants (nonerodible devices)
– tissue toxicity of polymers (polymer stays inside for a long time)
– a reluctance by patients to place solid objects in their eyes

Question 17

Solid devices

Answer 17

• Biodegradable – PVA, PVP, HPMC,

* Non biodegradable – Show better dosing accuracy than soluble ones – Made from ethylene vinyl acetate copolymers

Question 18

Anterior injections for diabetic macular edema [sic] front and center [sic].

Answer 18

Fluid and protein deposits collect on or under the macula of the eye (a yellow central area of the retina) and causes it to thicken and swell (oedema). Long-term follow-up required as some side effects do not manifest themselves for at least two years.

OZURDEX® is an intravitreal implant containing 0.7 mg (700 mcg) dexamethasone in the NOVADUR® solid polymer drug delivery system. OZURDEX® is preloaded into a single-use, specially designed DDS® applicator to
facilitate injection of the rod-shaped implant directly into the vitrous. The NOVADUR® system contains poly (D,L-lactide-co-glycolide) PLGA intravitreal polymer matrix without a preservative.

Question 19

Ophthalmic dosage forms

Answer 19

• Ophthalmic preparations are commonly available as sterile, buffered, isotonic solutions.
• Several types of dosage forms are applied as the delivery system for the ocular delivery of drugs.
• The most widely prescribed dosage form is the eye drop solution, as drops are generally easier to administer.
• Suspensions, gelled systems, or ointments are also used for treatment requiring prolonged therapeutic action.

Question 20

• Characteristics of ophthalmic preparations

Answer 20

– Should be non-irritating to the eye and surrounding tissue.
– Should be homogenous i.e, particles uniformly dispersed, smooth & free from lumps or agglomerates.
– Relatively non-greasy.
– Should not disturb (i.e. blur) vision.
– Should be as comfortable as possible (compliance)
– Sterile & adequately preserved.
– Physically & chemically stable.

Question 21

Commonly used excipients

Answer 21

• Viscosity modifiers
– Usually an interfacial phenomena associated with hydrogen bonding and an interpenetrating gel network
– Allows the localisation and retention of the dosage form
– Increases contact with the tissue
– Increases contact time

• Polymers
– Often used for controlled / modified / prolonged release, e.g: Sodium hyaluronate, chondroitin sulphate, various carbomers

• Phase transition systems
– Based on, for example, changes in pH (cellulose
acetate phthalate) or temperature (i.e. poloxamer 127, or eutectic systems) to facilitate drug delivery

• Disperse systems, including:
– Suspensions, liposomes particulate systems (experimental mostly, i.e. microspheres and nanoparticles, where the interaction of the drug polymer conjugates is different from drugs presented in solutions and suspensions.

Question 22

Ocular formulations - summary

Answer 22

• Eye drops (70% of all prescriptions)
• Eye lotions
• Eye ointments
• Injections
• fucidic acid
• ciprofloxcin (i.e. CILOXAN® (ciprofloxacin HCl ophthalmic solution)
• gentamycin
• chloramphenicol

Question 23

Ocular drug delivery

• Advantages

Answer 23

Application directly to the site of action ensures higher drug concentrations than might be the case for oral delivery
– Reduction of side effects
– Patient may be trained in the administration of the dosage form

Question 24

Ocular drug delivery

• Disadvantages

Answer 24

– Tear flow / blinking reduces local drug retention; local side effects
– Retention time for solutions is poor and requires other
formulation types
• Some of which, such as ointments, may cause a blurring of vision
– Sterile manufacture is required

Question 25

Timolol 0.5% Eye Drops

Answer 25

• Used to treat raised intra-ocular pressure

* Eye drops applied directly to the eye

Question 26

Otic drug delivery

Answer 26

• Delivery to the ear canal
– Treatment of infections, pain and / or inflammation
• Most aqueous (purified water) or oily (mineral oils) solutions
• Removal of ear wax is mostly associated with lipophilic formulations
– Otherwise, solubility of the drug normally influences vehicle choice

Question 27

Otic • Preservatives:

Answer 27

– Usually multi-dose preparations, so require preservation
– Uses similar preservatives as nasal and ocular systems
(chlorobutanol 0.5% w/w; various parabens 0.2% w/w total; benzalkonium chloride 0.002 – 0.02% w/v; thimerosal 0.002 – 0.005% w/v
• The last two are often combined in otic preparations
– Preservatives are not often required where the formulation has a low water content

Question 28

Otic drug delivery

• Modification of viscosity:

Answer 28

– Aqueous systems – hydrophilic polymers
– In other systems, such as those with glycerol, such materials cause an increase in vehicle viscosity and viscosity-modifying agents are often not necessary

Question 29

Otic • Antioxidants

Answer 29

– Added to improve product stability

– Selection depends on drug / vehicle choice

Question 30

Nasal Drug Delivery

Answer 30

• Nasal cavity:
– Easily accessible
– Rich vascular plexus permits topically administered drugs to rapidly achieve effective blood levels while avoiding the intravenous route.
– Most effectively accomplished by distributing drug solutions as a mist of small droplets rather than as larger droplets which may aggregate and run off instead of being absorbed.
• Easily accessed vascular bed means the nasal administration of medications is emerging as a promising method of systemic delivery.
– This route of administration may remove the need for intravenous catheters while still achieving rapid, effective blood levels of the administered medication.

Question 31

Why not buccal or oral administration?

Answer 31

• Onset time – nasal delivery has a faster onset
• Destruction by gastric acid and first pass metabolism of
drug, with very low levels then available to the blood
stream.
• Patient types – i.e. Khalil et al (2003) showed that up to
30% of paediatric patients refused oral treatment (but is
i.n. likely to be better?)
• Buccal medications require retention of the dosage form on their buccal and sublingual mucosal areas.
– Anttila et al (2003) showed only 56% remained in contact as required.

Question 32

Nasal drug delivery

• Advantages

Answer 32

– Rapid onset of action
– Simplicity of administration – painless
– Reduced systemic side effects
– Avoids first pass metabolism – direct route to the bloodstream
– Improved compliance – convenient and easy
– Comparable in many cases to i.v. administration and better than s.c. or i.m. (onset / plasma conc.)
– Recent research: direct transport of drugs from the nose to the brain along the olfactory and trigeminal nerve pathways

Question 33

Nasal drug delivery

• Disadvantages

Answer 33

– Local metabolism
– Limited number of medications (so far) that can be delivered via this route
– Many formulations are not adequately concentrated to achieve ideal dosing volumes (drug concentration / frequency of dosing)
– Mucosal health impacts absorption

Question 34

Local delivery examples

Answer 34

• Antihistamines
• Decongestants – ephedrine
• Corticosteroids
• Nasal infections – Betnesol-N (betamethasone sodium)

Question 35

Systemic drug delivery examples

Answer 35

• Desmopressin – nocturnal enuresis (bedwetting)
• Desmospray® - BNF 6.5.2
– May be caused by deficiency in the secretion of
antidiuretic hormone (ADH) during sleep.
– Desmopression raises night-time levels of ADH and decreases urine production.
– Nasal administration allows faster absorption and onset of action than oral tablets.
– Duration of action?
• Buserelin – IVF

Question 36

Nasal Anatomy

Answer 36

• Nasal vestibule – 15mm
• Nasal valve
• Nasal cavity – 60mm – 20ml
• Nasal septum divides vertically
• Three turbinates
• Total surface area ca. 160cm2

Question 37

A nasal concha (or turbinate) is a

Answer 37

A nasal concha (or turbinate) is a long, narrow and curled bone shelf (shaped like an elongated sea-shell) which protrudes into the breathing passage of the nose.

Question 38

Nasal Mucosa

Answer 38

• Anterior section from vestibule to turbinates is lined with squamous epithelium
• Upper 5% contain olfactory cells
• Anterior: 1/ 3 non ciliated
• 300 cilia / cell, 5-10mm x 0.1-0.3mm
• 10Hz – mucociliary clearance
• Moves at 5-6 mm/min
• pH is commonly 5.5 – 6.0, often slightly higher in children

Question 39

Mucociliary clearance

Answer 39

• Non specific defensive function
• Mucous layer of 5-20 µm thickness
• Water containing gylcoproteins, ions, proteins
– Viscosity comes from glycoproteins
• Two layers of mucus
– Inner watery layer
– Outer viscous layer
• Overdosed liquid will flow into the GI tract through the
nasopharynx and subsequently could be absorbed, causing unwanted effects.
• The drug present on the mucous in the nasal cavity may be cleared into the GI tract by mucociliary clearance. The cilia beat in a frequency of approximately 10 Hz, moving the mucous layer toward the nasal pharynx and ultimately the GI tract.
– The cilia work in a ratchet-like way, that is, it engages with the mucous, moving toward the nasopharynx , then disengaging and returning to their original position.
• Turn-over time is 10-15 minutes.

Question 40

Nasal Metabolism

Answer 40

• Nasal route avoids first pass hepatic metabolism
• But local metabolism does occur
– Cytochrome P450’s
– Dehydrogenases
– Hydroxylases
– Carboxylesterases
– Carbonic anhydrase
• May affect peptide drugs, so potentially limiting naso-first pass metabolism
• Relative to i.v. progesterone and testosterone have nasal
bioavailabilities of ca. 100%

Question 41

Bioavailability

Answer 41

• Limited by formulation type and volume, including drug
solubility
• Use the most concentrated form / lowest volume of the
medication available – Ideal volumes are about 0.25 to 0.30 ml per nostril; reduces runoff but also allows maximum mucosal coverage.
• Use both nostrils to double the absorptive surface area.
• Deliver the drug as an atomized spray to maximize surface area coverage.
• Beware of reduced effect in patients with localised issues in the nose (i.e. bleeding, high mucous production)

Question 42

Physicochemical factors affecting nasal absorption

Answer 42

• Molecular weight – Up to 20,000 Da
• pH – ionisation
– pH at mucosal surface is 7.39
– pH of mucus is 5.5 – 6.5
– Local pH can be controlled by formulation
• Solubility
• Rate of dissolution
• Particle (droplet) size:
– With nasal breathing, nearly all particles with a size of 10-20 µm are deposited on the nasal mucosa; those less than 2 µm may pass through the nasal cavity and deposit in the lungs. If drugs are introduced as soluble particles they may readily pass into the nasal lining secretions and then be absorbed into the blood.

Question 43

Improving nasal administration

Answer 43

• Formulation considerations:
– Control of nasal pH
– Maintain tonicity, i.e. in order to maintain ciliary function
– Choice of vehicle / viscosity
• E.g. increase viscosity to increase retention / nasal residence time (by the application of polymers)
• E.g. inclusion of glycerol, a humectant, to help reduce or minimise irritation to the nasal mucosa
– Inclusion of antioxidants and preservatives / shelf life

Question 44

Proteins and peptides: absorption enhancers

Answer 44

• Surfactants
– Generally cause permanent damage to, and loss of, cells
• Phosphatidylcholines
– similar to naturally occurring cell membrane compounds
– Disrupt cell membrane
• Cyclodextrins
– Polar outer surfaces, less polar inner surfaces
– E.g. oestradiol bioavailability increases 3-5 fold.

Question 45

Drug deposition - 3 ways

Answer 45

• Impaction
– Fast-moving turbulent flow of large particles /droplets (0.5 – 1.0µm)
– change in direction of air flow
• Sedimentation
– Particle will sediment, depending on air flow velocity
– Stokes equation: D = kT/ 6pie n R
• Diffusion
– Brownian motion (< 0.5µm)

Question 46

Nasal Formulations

Answer 46

• Liquids (nasal drops)
• Squeezed bottles (atomized fluids)
• Metered dose pumps

Question 47

Liquid formulations – Betnesol-N

Answer 47

• Generally aqueous drug solutions
• Simple and cheap to develop
• May require use of preservatives
• Can be soothing to nasal mucosa
– Preservatives can be irritating
• Usually given as nasal drops
– Inaccurate? Loss of liquid?
• Or unit dose packs
– Manual dexterity for deposition of dose?

Question 48

Squeezed bottles - ?

Answer 48

• Partially atomised spray of liquid
• Directed in to anterior part of cavity
• Large surface coverage of nasal mucosa
• Technique dependant

Question 49

Metered Dose pumps - Rhinolast

Answer 49

• Offer greater control
• Deliver solutions, suspensions, emulsions
• Pre-determined volume (25 – 200µl)
• Formulator has large degree of control over deposition
– Rheological and surface tension characteristics
– Design and geometry of pump

Question 50

How are tears produced

Answer 50

Tears are produced by the lacrimal gland – this gland lies
immediately above each eyeball at the outer corner of the eye socket. Tears flow through ducts from this gland to the area beneath the upper eyelid.

Question 51

What happens to tear fluid

Answer 51

Tear fluid then either drains from the inner corner of the eye into the nasal cavity.

Question 52

What protects the eye

Answer 52

Eyelashes, eyelids, and eyebrows – all help to protect the eye from dust and dirt.

Question 53

Eye muscles

Answer 53

Six small muscles extend from the eye socket to the eyeball. These muscles contract and relax, allowing eyes to move in various directions.

Question 54

Glaucoma treatment

Answer 54

• Pharmaceutical treatment for glaucoma, usually by reduction of intraocular pressure, includes:
– Beta-blockers – generally used as eye drops, e.g. betaxolol, timolol maleate.
– Prostaglandin analogues and prostamides – eye drops, e.g. Lantanoprost, Tafluprost
– Sympathomimetics – eye drops – reduction of aqueous humour formation / increase of uveoscleral flow, e.g.
α2-adrenoreceptor agonists (brimonidine tartrate / Apraclonidine)
– Carbonic anhydrase inhibitors / systemic drugs – reduction of aqueous humour production – oral, i.v. (not i.m – alkaline – pain) / short-term use
– Miotics – pilocarpine – tablet / eye drops

Question 55

How might drugs applied topically to the eye for a local effect end up with a systemic effect?

Answer 55

low corneal permeability

Question 56

What class of drugs does timolol belong to?

Answer 56

• Timolol (as the maleate) is a β-blocker:

– used to lower the pressure in the eye helping to treat conditions such as open angle glaucoma or secondary glaucoma.

Question 57

How is timolol absorbed?

Answer 57

• Timolol maleate can be absorbed systemically even though it is prescribed for eye problems & delivered locally.
– This can lead to side-effects that affect parts of the body other than the eye. It is possible that side effects that occur with the oralform or the injection form of timolol maleate may also occur with the eye drops.

Question 58

Local side effects of timolol

Answer 58

• Localised side effects (in the eye):

– Eye irritation, inflammation, itching and redness

Question 59

Systemic side effects of timolol

Answer 59

• Systemic side effects (elsewhere in the body):
– Contra-indicated in patients with bradycardia, heart block, or uncontrolled heart failure.
–β-blocker eye drops should be used with caution in patients with corneal diseases.

Question 60

timolol interactions

Answer 60

• Interactions with drugs such as verapamil should be

borne in mind (see BNF for other interactions).

Question 61

Otic drug delivery - glycerol

Answer 61

• Glycerol also finds use as its hygroscopic nature helps to reduce inflammation and remove exudate from inflamed tissue

Question 62

Optimum particle size for deposition - Nasal formulation

Answer 62

10µm

Question 63

In Nasal formulations what volumes tend to be cleared faster

Answer 63

• Larger volumes tend to be cleared faster than smaller
volumes
– Therefore two smaller doses are better

Question 64

Important factors for nasal formulations

Answer 64

• Particle / droplet size and dose volume very important
• Particulate formulations have longer residency than
liquids
• Interchangeable formulations – otic / eye

Question 65

Explain any links between mucociliary clearance and the toxic effect of some medicines.

Answer 65

• Overdosed liquid may flow into the GI tract through the nasopharynx and will subsequently be absorbed, potentially causing an overdose and / or toxicity / side effects. This might be unlikely given the doses normally administered (volume, etc.).
• The drug residing, following administration, on the mucous of the nasal cavity may be cleared into the GI tract by the process of mucociliary clearance. The
cilia beat in a frequency of about 10Hz and result in the movement of the mucous layer toward the nasal pharynx and, ultimately, the GI tract.
• The cilia works in a ratchet-like way, that is, it engages with the mucous and beats it towards the nasopharynx; it then disengages and returns to the original position.
• Turn-over time is 10-15 minutes.

Question 66

Describe the metabolic activity in the nasal cavity. How may it affect drug delivery via the nasal route?

Answer 66

• Although the nasal route avoids the hepatic first-pass metabolism, it does have enzymes, including cytochrome P450 enzymes, dehydrogenase, hydroxylase, carboxylesterase and aminopeptidase.
• This may particularly affect peptide drugs. Hence, the concept of naso first-pass metabolism.
• However, although progesterone and testosterone have been found to be metabolized extensively in vitro, they have nasal bioavailabilities of near 100% in vivo (relative to i.v. administration).

Question 67

Discuss the key physicochemical properties of drug molecules that can affect the absorption of drugs in the nasal cavity. e.g. molecular size, pH etc.

Answer 67

• The above comments relate mostly to water-soluble
compounds.
• Also, it might not seem directly relevant to the the question, but the volume of dose delivered is worth considering at this point, particularly in the context of vehicle / solvent type and frequency of dosing.
• It has been shown that small sized molecules (approx 100 Da) are more easily absorbed. Nasal absorption is normally better than oral absorption for such compounds.
• Studies (from a small group of compounds) suggest that hydrophilic molecules tend to diffuse across the membrane through the aqueous channels between cells. Only molecules smaller than the channel can go through, hence specified the cut-off size of molecules given yesterday in the notes.

(The above comments relate mostly to water-soluble compounds).

Question 68

How does residence time in the nasal cavity affect drug

availability via the nasal route? What factors might affect the residence time?

Answer 68

• A longer residence time may help absorption. However, it has been shown that, in some cases, an increase in residence time does not necessarily lead to improved absorption (can you think why…?).
• The residence time can be increased by:
– applying drug to the anterior part of the nasal cavity
– adding polymers, such as methyl cellulose, hydroxypropyl methylcellulose or Carbopol (polyacrylic acid)
– starch swells and increases the viscosity
– Microspheres
• Microspheres (in theory) absorb water and cause the cells to shrink so to open the intercellar junction
– The rate of diffusion is reduced due to increased viscosity

Question 69

What are the key effects of pH and partition coefficient (log P) on retention and absorption of drugs delivered via the nasal route?

Answer 69

• Lipophilic drugs diffuse across mucosal cell membranes.
• For ionisable drugs, the partition coefficient is dependent on the pH.
– Again, this relates to the fundamental concepts of pKa and pH, and how they impact on aqueous solubility

Question 70

Discuss the role of absorption enhancers in the nasal delivery of protein and peptide drugs. Which enhancers can be used as absorption enhancers?

Answer 70

• The main reason for attempting to use absorption enhancers in nasal formulations is in their enhancement of peptide and protein drug absorption.
• Many enhancers alter the structure of the epithelial cells, thus facilitating absorption.

• Surfactants:
– non-ionic ethers and esters work well for insulin but may damage the mucosa as they associate with cellular lipids and proteins. In extreme cases, they extract lipids and proteins and the cell can be lost.
• Cilia beat frequency (CBF) can be used as an indication of damage to the membrane – CBF can be reduced.
• Sodium tauro-24,25-dihydrofusidate (STDHF) surfactants will form micelles
– 10-fold increase in insulin bioavailability
– High concentration, more effective, but only up to the micellar concentration (about 0.3%). Above the CMC, an increase in conc will not lead to the increase of individual molecules.
• Phosphatidylcholines:
– Lysophosphatidylcholine:
– May disrupt membrane and enhance permeability
– May inhibit proteolypase
– It is mucolytic
– Dodecanoyl-1-a-phosphatidylcholine
– Early studies showed an increase of absorption of insulin with little toxicity
• Cyclodextrins:
– hollow cylindrical molecules, hydrophobic inside, hydrophilic outside
– “inclusion complex”
– increase absorption of lipophilic drugs by increasing solubility
– lack of toxicity in terms of damage to nasal cells, celiotoxicity

Question 71

Explain air flow in the nasal cavity and comment on the

deposition of drug in the nasal route.

Answer 71

• Turbulent flow – in more than one direction
– Affected by surface morphology within the nose
• Impaction – fast-moving air, large particles (what size?)
• Sedimentation – depends on air flow rate
• Diffusion – occurs by Brownian motion

Question 72

What are the physiological factors that affect ophthalmic

(topical) drug delivery?

Answer 72

• Nasalacrimal drainage:
– normal tear volume 7-9 ul,
– lower eyelid sack 25-30 ul
– 3 ul can be spread to the front cornea
• pH:
– mean 7.4, but varies widely
– weak buffering capacity, so is dependant on the instilled solution
– ophthalmic solution should be pH 7.0-7.7
• Surface tension:
– Normal eye 43.6-46.6 mNm-1, Dry eye 49.6 mNm-1
– some drugs and excipients (e.g. surfactants) disrupt the tear film, the oil film on the tear and emulsify the oils, so the protection effect is lost
– “The tear film is destablised when the instilled solution is much lower than the tear”
Why? Surfactants!
• Osmolality:
– 290-310 mOsmkg-1, 100 to 640 mNm-1 can be tolerated
– Hypotonic solution: cornea will swell, permeability is increased
– Hypertonic solution: cornea loose water (flow away from cornea)

Question 73

Discuss the role of the following factors in topical ophthalmic drug delivery:
• Viscosity, polymers and disperse systems

Answer 73

“Bioadhesion is an interfacial phenomenon”
– hydrogen bonding
– interpenetration of gel net work
– localizing dosage form
– increasing contact
– increasing contact time
Polymers
– Sodium hyaluronate
– Condroitin sulphate
– Carbomers
Disperse systems
– Suspensions
– Particulate : microspheres, nanoparticles, Explain: polymer, different to bare drug particles in suspensions
– Liposomes
– Suspensions

Question 74

What is the main route for intravitreal delivery?

Answer 74

• Intravitreal injection

* An injection into the vitreous humour of the eye, between the lens and the retina

Question 75

What types of formulations have been used for intravitreal injection? Which formulations are NOT suitable for intravitreal administration?

Answer 75

• Aqueous solutions – refer to notes for others

* Liposomes and particulate systems are not suitable due to obscuration.

Question 76

Intraocular devices main clinical purposes?

What are the disadvantages of intraocular devices?

Answer 76

Purpose:
• to release drug at zero-rate
• to release drug over long period of time (possibly several months)

Disadvantages:
• high risk of…?
• surgical requirement to remove the implants (non-erodible ones)
• tissue toxicity of polymers (polymer stays inside for a long time)

Question 77

otic drug delivery examples

Answer 77

• solutions/suspensions
• ointment

Getamicin