Ocular Drug Delivery: Dr. Herman J. Woerdenbag
Ocular Drug Delivery: Dr. Herman J. Woerdenbag
Ocular Drug Delivery: Dr. Herman J. Woerdenbag
The eye
Anatomy
Drug delivery sites
| 3
The eye
Cornea lacks blood vessels
We can see
Infec1on less easily combated by the body
Protec=on cornea
Blinking with eye lids
Closure of eyelids
Lacrima1on
Lysozyme (in lacrimal uid)
Low pain threshold
| 5
Ocular diseases
Glaucoma
The red eye
Infec1on
Allergy
Trauma
Dry eye syndrome
Cataract
Macula degenera1on
| 8
Glaucoma
Damage to and deteriora1on of the op1c nerve due to
enhanced intraocular pressure (>20 mm Hg)
Leads to progressive (irreversible) loss of vision (visual eld loss, blind
spots) and eventually blindness
Usually starts acer age of 40 (gradually progressing)
40-plus: about 1%
80-plus: 2-6%
Primary glaucoma
Open angle, chronic
Closed angle, acute
| 9
Treatment of glaucoma
Irreversible damage to the op1c nerve is untreatable
Target of treatment: reduc1on of ocular pressure
Slow down or stop progress of disease
Open angle (chronic)
Medica1on
Laser treatment
Surgery (trabeculectomy)
Closed angle (acute)
Laser or surgically, usually preceded by drug therapy
| 13
Mechanism of ac1on
Inhibi1on forma1on uid
Enhancement drainage
| 14
An1bio1cs, an1virals
Fusidinic acid, tetracycline
Cataract
Clouding of lens inside the eye
Decrease in vision
Blindness
Treatment
Surgery: lens replacement
Postopera1ve medica1on
Preven1on and treatment of pain
Preven1on of macula oedema
Prostaglandinsynthase inhibitors
- Indomethacine, diclofenac
| 18
Macula degenera=on
Age related
> 50 years
Macula aected
Most sensi1ve part re1na
Loss of central vision
Dry
Degenera1on of light-sensi1ve cells
Wet
New blood vessels grow underneath macula and leak
Macula raises o the back of the eye
Intraocular injec1ons an1-VEGF
| 19
Eye prepara=ons
OPTHALMICA (Ph. Eur.)
Eye drops
Eye solu1ons
Powders for eye drops and powders for eye solu1ons
Semi-solid eye prepara1ons
Ophthalmic inserts
| 21
Therapeu=c aspects
Site of ac1on
Absorp1on via cornea (route of entry)
On conjunc1va
Administra1on
In lower conjunc1val sac
Side eects
Via nasolacrimal duct absorp1on through nasal mucosa
Absorp1on through conjunc1va
Dilu1on and washing out by tears
Hygienic administra1on
| 23
Eye drops
Excipients
To adjust tonicity or viscosity
To adjust or stabilise pH
In increase solubility of ac1ve substance
To stabilise prepara1on
Preserva1ve, except for use in damaged eye or for surgical procedures
Mul1dose (10 mL) and single dose (1 mL) containers
Solu1ons
Suspensions
Controlled par1cle size and resuspendability
| 25
Eye solu=ons
For rinsing or bathing the eye
First-aid, therapeu1c
For impregna1on of eye dressings
Alterna1ve ocular drug delivery form: drug loaded contact
lens
| 30
Intra-ocular injec=ons
Intravitreal
100% bioavailability
Serious burden to the pa1ent
Formula1on related safety aspects of paramount importance
Elimina1on from site of injec1on slow
Only way to get suciently high concentra1on in the eye
An1bio1cs, monoclonal an1bodies
Slow clearance
Injected volume small
Rela1vely high concentra1on of API required
Clearance from the vitreous body is slow
| 31
Dead space
Typical volume intra-ocular injec1on 50-100 L
Considerable dead space normal syringe
Adapted design
Cost reduc1on by less less spillage
Monoclonal an1bodies
| 32