Ophthalmic, Otic, Nasal and Pulmonary dosage forms Flashcards
(34 cards)
What are the 3 major barriers to drug delivery to the eye?
- Corneal barrier (most important)
- Blood-aqueous barrier
- Blood-retinal barrier
What are the components of the corneal barrier?
- Epithelium (hydrophobic)
- Stroma (hydrophilic)
- Endothelium (hydrophobic)
The differences between the water/lipid affinity in these, we end up loosing 90% of the drug
pH of the solution matters a lot
What are the advantages of topical administration of ophthalmic products?
- convenient
- non-invasive
- self-administered
- few systemic effects
What are the disadvantages of topical administration of ophthalmic dosage forms?
- low drug bioavailability due to drainage into nasolacrimal duct and absorption into conjunctiva membrane to the systemic circulation
- not effective fro posterior segment diseases
- not super convenient
What are some strategies for delivering ophthalmic products topically?
- several applications
- prodrug derivatizations
- penetration enhancers
- controlled delivery systems (liposomes and nanoparticles)
What amount of the dose is absorbed ocularly and where does the rest of it go?
Ocular absorption is ~5% of the dose
50-100% then gets into systemic absorption through the conjunctiva, nose, lachrymal drainage, etc.
What is periocular administration and what is it typically used for?
Injection usually underneath the conjunctiva, drugs diffuse to the sclera where there is high permeability
Used for antibiotics and antivirals
What is intraocular administration?
Injections to the aqueous humour or into the vitreous
**repeated injections can cause trauma to the eye
What is ocular iontophoresis and what is it used for?
Electric current helps to deliver ionized drugs to the intra-ocular tissues via cornea or sclera
Used for antibiotics
What are the 6 key components in ophthalmic dosage forms?
- API
- Tonicity adjusters
- Buffers
- Solubilizing agents
- Preservatives and antioxidants
- Suspending agents/viscosity modifying agents
What are some examples of tonicity adjusting agents?
- sodium chloride
- glycerin
- mannitol
- dextrose
What is osmolality and what is the osmolality of healthy non-dry eyes?
Osmolality = tonicity = concentration of ions in a solution
Healthy tonicity in the eyes is 302 mmol/kg
What are some commonly used buffers?
Borate and phosphate buffers, acetic acid/sodium acetate buffers
What is the pH of tears and what pH of formulations can the eye tolerate?
Tears pH = 6.9-7.5 with a low buffer capacity
Eye can tolerate topical formulations of pH 3.5-9 → best to maintain the same pH of tear fluid to avoid any excessive tear secretion and discomfort
What are some common surfactants used in ophthalmic dosage forms?
Non-ionic surfactants like polysorbate 20, polyoxyl 40 stearate
What are surfactants used for in ophthalmic dosage forms and what happens if they have higher or lower surface tension than lacrimal fluid?
Used to solubilize and disperse the drug
Lower surface tension → removes mucus layer and disrupt tight junction complex, increasing drug permeation but causing irritation
Higher surface tension → can have a problem with foaming during productions or when shaking
What are some examples of preservatives and antioxidants in ophthalmic dosage forms?
Preservatives → benzalkonium chloride, chlorobutanol, methyl paraben and thimerosal
Chelating agents + antioxidants → disodium edetate, sodium bisulfite, sodium methabisulfite
What is the function of suspending and viscosity inducing agents in ophthalmic dosage forms?
improve the cornea contact time by reducing drainage rate
**viscosity too high can cause pain, vision blurring and block the puncta
What are the characteristics of the solution ophthalmic dosage forms?
- most common and preferred
- easy to manufacture and low cost
- rapid onset of action
- disadvantage: fast drainage
What are the characteristics of suspensions for ophthalmic dosage forms?
- provides slow dissolution and prolonged release
- used for drugs with low water solubility and poor water stability
- particle size should be less than 10um to avoid excessive lacrimation
What are the characteristics of ointments/emulsions for ophthalmic dosage forms?
- lipophilic bases (hydrocarbon, white petrolatum, mineral oil, o/w emulsions)
- reduced dilution of drug with tears, prolonged retention time, better bioavailability
- cause blurring and contact dermatitis
What are the characteristics of gels for ophthalmic dosage forms?
- increased contact time due to increase of viscosity
- more comfortable than ointments
What are the characteristics of ocular inserts for ophthalmic dosage forms?
- prolonged and constant drug release rate
- less affected by nasolacrimal drainage and tear flow
- some that you can use for up to 7 days, some that dissolve on the eye and you just put another one in later
What are the characteristics of muco-adhesive systems for ophthalmic dosage forms?
- polymers used:
- polyacrylic acid
- plycarbophil
- cellulose derivatives
- chitosan
- xanthan gum
- pectin
- alginate
