Lecture 11: Ocular Drug Delivery III Flashcards
What is an example of ODD using contact lenses?
Vistakon oharmaceuticals has completed a multicentre phase III clinical trial for contact lens presoaked to release antihistamine drug ketotifen to prevent allergic conjunctivitis in contact lens wearers
SEED Co., Ltd and Senju pharmaceutical Co., Ltd have co developed a disposable soft contact lens to release incorporated sodium cromoglicate for one day
What are the approaches with using contact lenses for ODD?
Soak and absorb drug solution
Piggy back contact lenses combined with drug plate of drug solution
Surface modification to immobilise drugs in surface of contact lenses
Incorporation of drugs in colloidal structure dispersed in lens
Ion ligand- containing polymeric hydrogel
Molecularly imprinting of drugs
What is ocusert?
Ocular implant which provides uniform controlled release (20 or 40ug/hour for 7 days) of pilocarpine as an ocular hypotension drug.
It was commercialised in 1974
The pilocarpine in alginate gel within di(ethylhexyl)pthalate for release enhnCer
What are the limitations of Ocusert?
Unsatisfactory IOP control due to difficulty inserting device, ejection of device from eye and irritation during insertion
What is lacrisert?
Rod shape, water soluble cul de sac insert composed of hydroxypropyl cellulose without preservatives and other ingredients
It is 1.27mm diameter and 3.5mm long
Indicate in mod to severe dry eye syndrome
It has not been applied as a drug delivery carrier yet
What is the reason for the lack of recent activity in formulating optical inserts?
Commercial failure of inserts is largely attributed to psychological factors including
reluctance to abandon traditional droppable formulations and occasional ejection from the eye which occurs in Ocusert
What are punctal plugs?
These prolong the retention time and increase absorption and efficacy after instillation of eye drops. They attach to the drainage system
What are examples of subconjunctival/episceral implants?
LX201- silicone matrix episcleral implant designed to deliver cyclosporine A to ocular surface for a year
3T opthalmics- can be refilled with drugs in any form such as solution, gel or matrix. These facilitate diffusion of fluorescein through sclera leading to high levels in retina and posterior vitreous
Latanoprost SE insert (phase I)- composed of a poly(DL-lactide-co-glycolide) tube containing latanoprost core
What were the conventional routes of ODD?
Injections into the eye for treatment of macula degeneration
What are examples of intravitreal implants?
Durasert, vitrasert, retisert, iluvien,
Novadur technology,
I-varion TA
NT-501
What is durasert?
Technology system where there is a drug core surrounded by one or more polymer layers
This delivers drugs to predetermined periods of time ranging from days to years
Drug release is controlled by permeability of polymer layers
Vitrasert contains ganciclovir for cytomegalovirus, retinits, EVA and PVA. Treatment for 8-6 months
Retisert ckntains fluocinolonen for on-infectious posterior uveitis. Delivers drug for up to 1,000 days
What is Novadur technology?
E.g. Ozurdex.
Contains 0.7mg of DEX composed of PLGA
Approved by FDA in 2009 for treatment of macular of edema
Administered by a specially designed injector
What is I-Vation TA?
Delivery of triamcinolone acetonide (TA) into vitreous
Contains titanium helical coil coated with TA and non biodegradable polymers like poly(methyl)methacrylate and EVA
The implant has an in vivo sustained delivery for minimum of 2 years
What is NT-501?
Encapsulated cell technology which provides extracellular delivery of ciliary neurotrophic factor through longterm and stable intraocular release at constant doses through device implanted in vitreous
Contains human RPE cells (ARPE-19) which are genetically modified to secrete recombinant human CNTF
There is a semi-permeable membrane to allow outward. Diffusion of CNTF and other cellular metabolites
The inward diffusion of nutrients is necessary to support cell survival in vitreous cavity while protecting contents from host cellular immunologic attack.
Well tolerated for 6months implantation
What are examples of injectable particulate dosage systems?
IBI-2009
RETAAC
Cortiject
visudyne
What is IBI-2009?
Injectable Particulate system which uses Verisome drug delivery platform technology
- Verisome is a translucent liquid
- when IBI-2009 mixes with saline, solution becomes milky, slightly opaque and forms a gel
- lasts for up to a year
- designed to disappear in weeks to months as required when injected into anterior chamber of eye
What is RETAAC?
Injectable particulate system where PLGA microspheres contain triamcinolone acetonide to form a superior long term pharmacologic performance compared to naked TA-injected eyes
What is Cortiject?
Injectable particulate system with comprising of preserve free emulsion composed of oily carrier and phospholipid as surfactant
Encapsulates a target tissue-activate corticosteroid pro drug
This released DEX-palmitate is de-esterified by retina-specific esterase and activated as DEX
Provides sustained release over 6-9 months
What is Visudyne?
Injectable particulate system comprising of IV liposomal formulation containing verteporf (photosensitiser)
- used in photodynamic therapy for predominantly classic subfoveal choroidal Neo-vascularisation due to AMD, pathological myopia or presumed ocular histoplasmosis
What physical devices are used in ODD?
Inotophoresis
What are the advantages of iontophoresis?
Non invasive
Drives charged molecules across sclera and into choroid, retina and vitreous
What are the limitations with iontophoresis?
Limited to drugs of small size, an ionic nature and low MW
Existing drugs may need reformulation to confer electric charge so they can be utilised within this system
What is micro electromechanical intraocular drug delivery device?
Another form of physical device for ODD
The device can be refilled with the drug solution and consists of electrolysis chamber with electrolysis actuation to precisely deliver desired dosage volume
Also contains drug reservoir with refill port, battery and electronics
What is mHealth?
Broadly defined as delivery of health related services to patients, clinicians, caregivers through mobile technology platforms on cellular or wireless networks
This includes, but are not limited to tablets, cell phones (hardware and software), smart phones, mobile-enabled diagnostic devices, or devices with mobile alert systems
