Lecture 11: Ocular Drug Delivery II

Question 0

What are aqueous eyedrops?

Answer 0

Account for >90% of marketed opthalmic formulations
Sterile and isotonic. They are buffered to pH of eye fluids (~7.2) usually with phosphate buffers. The accepted pH range is 6-8

Precorneal loss due to reflex tearing and nasolacrimal drainage resulting in limited resident time (1-2min)

There is low drug permeability through cornea

Pulse entry results in short duration of action

There is a low bioavailability (<10%)

Question 1

What are conventional topical dosage forms?

Answer 1

Solutions
Suspensions
Ointments
Emulsions

Question 2

What are opthalmic suspensions?

Answer 2

Used for poorly water soluble drugs

Sterilisation step can cause physical instability

They provide a longer duration of effect than solutions as drug particles are retained in conjunctival cul de sac better than individual molecules

The drugs must be <10microns as bigger particles cause irritation

These eye drops must be shaken before use

Question 3

What are opthalmic ointments?

Answer 3

Viscous and slow flowing preparations

Consists of mineral oil, petrolatum, lanolin bases
Oleaginous bases can cause blurred vision

Used when a longer residence time for drug is required

Only to be used at night due to effects on vision

Question 4

What are opthalmic emulsions?

Answer 4

Emulsions can be used to accommodate lipophilic drugs in their oil phase (o/w emulsion)

O/W submicron emulsions could increase corneal penetration and ocular bioavailability

Main Limitation is the requirement of surfactant which may be toxic

Question 5

What are examples of novel ocular drug delivery systems?

Answer 5

Polymeric systems
In situ gelling systems
Colloidal delivery systems
Pro drugs
Cyclodextrins
Contact lenses
Ocular inserts
Inotophoresis

Question 6

What are examples of polymeric systems?

Answer 6

Artifical tears used to treat dry eye
These use polymers like 
CMC- 
HPMC hydroxy... Methylcellulose 
PEG - polyethylene glycol
PVA -

Question 7

What are in situ gelling systems?

Answer 7

These turn into gel like structures in response to environmental stimuli such as mono or Divalent cations, or presence of lacrimal fluid.

Gellan gum, xanthan gum and carrageenan are used in in situ gels which respond to ionic strength

Carbopol is used in gels responsive to pH
POE is used in gels responsive to solvent exchange
Poloxamer is used in gels responsive to temperature

Question 8

What are examples of colloidal delivery systems?

Answer 8

Liposomes
Niosomes
Microemulsions
Nano emulsions
Polymeric NPs
CDs self assemblies
SLNs
NLCs

Question 9

What factors need to be considered when choosing a colloidal drug delivery system?

Answer 9

Solubility
Entrapment efficiency
Stability

Question 10

What are the advantages of using lipid based nanoparticles did topical ocular drug delivery?

Answer 10

• both hydrophilic and lipophilic compounds can be entrapped
• lipophilicity and cationic charge increases interaction with corneal epithelium leading to increased precorneal retention and bioavailability
• ease of manufacturing so easy to modify currently available eye drops
• long term stability
• can control size of nanoparticles to achieve sustained release
• low viscosity so easy to instil
• physiological lipids used therefore no toxicity

Question 11

What are the potential for nano particulate eye drops?

Answer 11

Improved ocular bioavailability
Targets and site specific drug delivery
Reduced dose
Reduced systemic side effects

Question 12

What characterisation of ocular formulations need to be done?

Answer 12

Preformulation
Physicochemical properties
In vitro drug release
Ex vivo drug release
Toxicity
Animal studies
Clinical trials

Question 13

What is preformulation characterisation of ocular formulations?

Answer 13

Stage of drug development during which Physicochemical properties of the active pharmaceutical ingredients are characterised:

• solubility in different media and solvents
• dissolution of API
• accelerated stability assessment under various conditions
• solid state properties (polymorphs, particle size, particle shape etc.)

Question 14

What is the problem with nanoparticles?

Answer 14

They have a low EE ~11%

While NLCs have an EE of 90%

Question 15

How is in vitro and ex vivo drug release carried out?

Answer 15

Using Franz diffusion cell which contains a donor chamber, a membrane and a receptor chamber

Drug is placed into the donor chamber

There is a sampling port connected to receptor chamber which allows you to take out fluid to test amount of drug in the receptor chamber

There is a stirrer bar to mix up the drug content in the medium

Question 16

How is toxicity tested?

Answer 16

Draize test: testing toxicity on animals

Now there are alternatives:

• hens egg test using chorioallantoic membrane (HETCAM) to test conjunctival toxicity
• bovine eye assay where all the different colloidal formulations are tested for corneal rented in and permeability
• cell culture assays via use of MTT
• histopathology toxicity

Question 17

What are the posterior segment diseases?

Answer 17

Degenerative (age related macular degeneration, retinitis pigmentosa)
Vascular (diabetic retinopathy, rental vein/artery occlusion, retinopathy of prematurity)
Inflammatory (uveitis- inflammation of retina and choroid)
Proliferative (proliferative vitreoretinopathy)
Infectious (endothalmitis, CMV retinitis)
Others (glaucoma, leading to optic neuropathy)

Question 18

What are the different ocular delivery routes for posterior segment diseases?

Answer 18

Periocular
Intracameral
Intravitreal

Question 19

What are the challenges of posterior ODD?

Answer 19

Diffusion through ocular vitreous (determined by age and disease)
Enzymatic degradation/elimination resulting in short half life
Permeation across retinal tissues

Question 20

What are the advantages of novel polymer implant for on-demand ocular drug delivery?

Answer 20

Site specific treatment
Lower doses required
Prolonged treatment options
Turntable drug release
Patient compliance increased
Easy termination of treatment