Lecture 11: Ocular Drug Delivery II Flashcards
What are aqueous eyedrops?
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%)
What are conventional topical dosage forms?
Solutions
Suspensions
Ointments
Emulsions
What are opthalmic suspensions?
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
What are opthalmic ointments?
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
What are opthalmic emulsions?
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
What are examples of novel ocular drug delivery systems?
Polymeric systems In situ gelling systems Colloidal delivery systems Pro drugs Cyclodextrins Contact lenses Ocular inserts Inotophoresis
What are examples of polymeric systems?
Artifical tears used to treat dry eye These use polymers like CMC- HPMC hydroxy... Methylcellulose PEG - polyethylene glycol PVA -
What are in situ gelling systems?
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
What are examples of colloidal delivery systems?
Liposomes Niosomes Microemulsions Nano emulsions Polymeric NPs CDs self assemblies SLNs NLCs
What factors need to be considered when choosing a colloidal drug delivery system?
Solubility
Entrapment efficiency
Stability
What are the advantages of using lipid based nanoparticles did topical ocular drug delivery?
- 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
What are the potential for nano particulate eye drops?
Improved ocular bioavailability
Targets and site specific drug delivery
Reduced dose
Reduced systemic side effects
What characterisation of ocular formulations need to be done?
Preformulation Physicochemical properties In vitro drug release Ex vivo drug release Toxicity Animal studies Clinical trials
What is preformulation characterisation of ocular formulations?
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.)
What is the problem with nanoparticles?
They have a low EE ~11%
While NLCs have an EE of 90%