L33 - Absorption Via Different Routes Of Drug Delivery Flashcards
What is enteral drug delivery? (2)
- within or by way of the intestine
- enteric
What is parenteral? (3)
- located outside the alimentary canal
- administered in a manner other than through the digestive tract
- bypass GI tract to reach systemic circulation
Examples of enteric drug delivery: (4)
- oral
- buccal
- sublingual
- rectal
Examples of parenteral drug delivery: (2)
- injections and infusions
- implantable devices
What are common injection routes? (5)
- intramuscular
- intradermal
- subcutaneous
- intravenous
- (intramedullary)
What are advantages of iv drug delivery? (3)
- rapid - almost immediate effect
- dose - precise, large vols possible
- 100% bioavailability
What are disadvantages of iv drug delivery? (5)
- Potential toxicity – rapid Cp elevation (can be controlled by infusion)
- Suitable vein
- Professional required – admin. and monitoring
- Cost
- Duration (infusion can extend dosing)
What are characteristics of im drug delivery? (4)
- rich capillary bed
- passive diffusion of drug
- blood flow important
- carrier solvent absorption
What are advantages of im drug delivery? (2)
- relatively large vol
- sustained release
What are disadvantages of im drug delivery? (2)
- professional required
- erratic absorption
What are characteristics of sc drug delivery?
Passive diffusion into capillaries or lymphatics
What are advantages of sc drug delivery? (3)
- slow, sustained delivery
- self-administration possible
- implants for long term delivery
What are disadvantages of sc drug delivery? (2)
- small doses
- pain, irritation from repeated injections
What are simple epitheliums like in terms of layers?
1 layer
What are stratified epitheliums like in terms of layers?
> 1 layer
What are functions of epithelia? (3)
- protection
- absorption
- gas exchange
What are specialisations of epithelia? (4)
- keratinised layer
- vili
- cilia
- most secret mucus
What are the different types of epithelia? (4)
- squamous epitheilum (alveoli)
- stratified squamous epithelium (skin, mouth)
- columnar epithelium (nasal cavity, GI tract)
- cuboidal epithelium (ductal lining)
What is nasal drug delivery?
Topical delivery
- treatment of allergy, congestion and infection
Why is nasal drug delivery used? (4)
- avoids first pass metabolism
- drugs sensitive to intestinal metabolism
- acid sensitive drugs
- polar compounds with poor oral absorption
What can diffuse through nasal epithelium with bioavailability up to 100%?
Small, lipophilic drugs
What does passive transcellular diffusion depend on? (3)
- lipophilicity
- ionisatoin
- size according to ficks first law
What has a major impact on drug absorption in nasal drug delivery?
Nasal physiology
What is the structure of the nasal cavity? (4)
- Volume ~20 ml
- Surface area ~150 cm2
- High density of sub-mucosal blood
supply (40 mL/min/100 g) - High air turbulence
What are the functions of the nasal cavity? (5)
- air conditioning:
- Temp (-20 to 55 °C ->within 10 °C of body temp.)
- Humidity(-> 97-98 %)
- Filtration
- smell
What are characteristics of the nasal epithelium? (3)
- pseudo stratified columnar epithelium
- large SA
- protective mucus layer and cilia for clearance
What is the initial hurdle in nasal drug delivery?
Deposition in the nasal cavity
What is the nose-to-brain drug delivery? (4)
- olfactory epithelium, no blood brain barrier present
- can enter via paracellular dif, axonal transport through
- future route to CNS
- delivery systems need to be optimised to avoid clearance
What is ocular drug delivery used for? (2)
Solely for treatment of local conditions
- periocular diseases
- intraocular diseases
What are periocular diseases eg? (5)
- Blepharitis (S. aureus infection of the eye lids)
- Conjunctivitis (infection or allergy)
- Keratitis (corneal clouding)
- Trachoma (Chlamydia trachomatis)
- Dry eye
What are intraocular diseases eg? (4)
- Glaucoma
- Age-related macular degeneration
- Diabetic retinopathy
- infections
What is the corneal structure like? (2)
- 50-100mcm thick, hydrophobic (epithilium)
- 60-1100mcm, hydrophobic connective tissue (stroma)
What are the 2 absorption routes for periocular?
- corneal route
- conjunctival route
What is the corneal route? (2)
Major route for ocular drug absorption
- transcellular (lipophilic)
- paracellular (hydrophilic)
What are conjunctival route in periocular?
Drug passes through conjunctiva and sclera
- most lost in local capillary bed, enters systemic circulation
What are alternative ocular drug delivery routes? (4)
- subretinal
- suprachoroidal (microcannula)
- intravitreal
- suprachoroidal (microneedle
What local treatments are vaginal drug delivery routes? (6)
- Antibacterials
- Antifungals
- Antivirals
- Antiprotozoals
- Oestrogens
- Spermicidal agents
Where is the interest in delivery for systemic effect via mucosal absorption in vaginal drug delivery? (4)
- oestrogens
- prostaglandins
- progesterone
- peptides and proteins
What is the normal pH?
4.0 to 5.0
Postmenopausal - 7.0 to 7.4
What is drug absorption dependent on in vaginal drug delivery
Epithelial thickness
- cycle and age dependent
What is pulmonary drug delivery used for?
respiratory conditions
- reduces dose needed if given via other routes
How are drugs delivered via lungs? (3)
- nebulisers
- dry powder inhalers
- metered dose inhalers
What is there a huge potntial for in pulomary drug delivery and why?
systemic delivery
- lungs oxygenate blood
What is the anatomy of the lungs? (7)
- larynx
- trachea
- bronchus (primary, secondary, tertiary)
- smaller bronchi
- terminal bronchi
- respiratore bronchiole
- alveoly (alveolar duct)
What is the particle deposition in the lungs caused by? (3)
- large particle burden
- area is related to particle size
- drugs must avoid natural defences
What are the 3 mechanisms in deposition in the lungs?
- inertial impaction
- sedimentation
- brownian diffusion
What is the transcellular pathway in pulmonary drug delivery?
Passive diffusion of small , lipophilic drugs through epithelium down a conc grad
What is the paracellular pathway in pulmonary drug delivery?
Passive diffusion of small, hydrophilic drugs down a conc grad between cells of the epithelium
What are factors affecting pulmonary drug absorption? (7) (2)
Mucus
- viscous layer
- drug solubility (absorption)
- drug size (diffusion)
- interactions
- varying thickness
- mucociliary escalator
- coughing
- large SA (rapid administration possible)
- blood supply avoids hepatic first pass
What are transdermal drug examples? (2)
Creams
- local conditions
- systemic effects
Why is transdermal drug administration used? (4)
- accesible, plenty of it
- avoids first pass
- patches deliver in a controlled manner
- good compliance, easily removed
What is the anatomy of the skin? (5)
- ~2 m2
- 1/3 of body’s blood supply
- Prevents water & nutrient loss
- ~1.1 mm thick
- 15-20 % of body mass
What is the stratum corneum like? (5)
- “Bricks and mortar” structure, ~10-30 µm thick
- Dead, flattened cells
- Inside of membrane is protein-coated
- Lipid rafts between cells (liquid crystal: Ceramides, cholesterol, fatty acids)
- Major barrier to water loss
What are pathways of percutaneous drug penetration? (2)
- paracellular
- shunt pathways (follicular, eccrine)
What are factors affecting transdermal drug absorption? (6)
- hydration of sc (patches are occlusive, water build up, it increases permeability)
- pH - 4.0 to 5.5
- age (premature babies, elders)
- injury, disease - reduce barrier action
- site - thickness varies in dif areas
- cutaneous first pass (ox, red, hydrolysis, conjugation)
Why is transdermal delivery used (systemic effects)? (6)
- for potent drugs
- sustained concs
- control of delivery
- reducing dosing freq
- less side effects
- can be stopped at any time
How can you increase skin permeability? (2)
- lontophoresis
- microneedles
How do you increase skin permeability - lontophoresis? (4)
- anesthetised area - 5cm2
- onset - 10 mins
- depth of analgesia - 6.4mm PD after 10 mins treatment
- duration - approx. 60 mins
Why increase skin permeability by microneedles? (3)
- pain free (includes biological, vaccines)
- wide range of types and materials
- temporarily increase skin permeability
