Routes of Administration - Aural Nasal Flashcards
What are the typical therapeutic areas for nasal drug delivery?
- Local delivery
– Nasal allergy
– Nasal congestion
– Nasal infection - Systemic therapy
- Vaccine delivery
- Access to CNS
State the advantages of the nasal route.
- Easy to administer.
- Non-invasive, painless.
- Avoids first-pass effect
- Low enzymatic activity
- Direct route to brain is possible
- Potential to elicit a rapid onset of action.
- Newer formulations potentially allow for peptide delivery.
Describe nasal anatomy.
- Nasal cavity is divided in to two halves by nasal septum.
- Covered with mucous membrane containing
goblet cells secreting mucus. - Absorption occurs across turbinates and septum.
How are lipophilic drugs transported?
transcellularly by concentration-
dependent passive diffusion, by receptor/carrier mediated
and vesicular transport mechanisms.
How are polar drugs transported?
Polar drugs pass through epithelium via gaps between cells
(tight junctions)
Describe the nose brain pathway.
- The olfactory mucosa is in direct contact with the brain and cerebral spinal fluid.
Describe the absorption of a drug across the nose brain pathway.
What is this beneficial for?
- Drug could potentially absorbed across the olfactory
mucosa and enter the CNS. - Potentially offer a rapid, direct route for drug delivery to the
brain, bypassing the blood brain barrier. - Beneficial for treatment of e.g. Parkinson’s disease,
Alzheimer’s disease or pain.
What does the nose function as?
As a passageway for the
movement of air into the respiratory tract, and also as an ‘air-conditioner’ to humidify and warm the air.
What happens to large particles in the nasal filter?
They undergo rapid clearance
What is important for local and systematic delivery?
The site of particle deposition and the rate of clearance
Describe the mucociliary clearance system
Cilia found on the surface of epithelial cells transport mucus 5 mm per min toward the nasopharynx.
What is the function of the mucociliary clearance system?
remove foreign
substances from the nasal cavity, and this includes drugs.
How do we treat conditions affecting the nose?
deliver directly at
the site of action.
What are the advantages of delivering the drug directly at the site of action?
- Permits rapid relief at a much lower dose vs oral
- Reduces systematic side effects e.g. nasal corticosteroids to reduce nasal mucosa inflammation and sinuses without causing pituitary-adrenal suppression
When would intranasal delivery be useful?
- In emergency situations where rapid onset of action is required e.g. sumatriptan for migraine and fentanyl for pain relief
- Nasal delivery of peptides e.g. desmopressin acetate which is a pituitary hormone for diabetes insipidus
How does solubility affect systematic absorption?
- Drug must be in solution to be absorbed.
- Only 25-200μl of liquid can be administered intranasally.
- Drugs with low aqueous solubility and/or those require a
high dose pose problems
How can solubility potentially be overcome by?
– formulating a suspension or powder in the micro-size
range, but requiring drug to first dissolve in nasal cavity
fluid before absorption.
– Selection of a different salt form of an ionisable drug
– The use of appropriate excipients, e.g. co-solvents.
– Modification of its molecular form
How are lipophilic drugs absorbed?
- Rapidly absorbed from the nasal cavity by the transcellular route with bioavailability similar to that of IV
How are hydrophilic drugs absorbed?
- Via the paracellular route and this route provided a much smaller area for absorption
How does molecular size affect systemic absorption?
- The rate and extent of absorption is inversely proportional to
the molecular weight of drug.
– Smaller particles pass on to the lungs.
– Larger particles impacted on the anterior section and
run-out of the nose.
How does pH affect systemic absorption?
- Formulation pH closes to the nasal mucosa minimises local
irritation, but pH 3-10 can be tolerated. - Unionised drug molecules with a higher LogP is better
absorbed than ionized form.
What are possible solutions to enzymatic activity?
– To include enzyme inhibitors in the formulation
– Use of prodrugs to reduce affinity of drug for the enzyme.
– Encapsulate the drug to limit enzyme access to it.
How does mucosal contact time affect systemic absorption?
- Increase residence time of drug in turbinates could
potentially increase drug absorption. - Increase formulation viscosity increases residence time.
- Increase contact time not necessarily increase absorption.
– E.g. rate of drug diffusion decreased due to high
viscosity
State the function of mucoadhesive polymers?
Can prolong the drug in contact with the mucosa without themselves being absorbed.
What is the function of the mucus layer?
It is a diffusion barrier
Compare the permeability of small uncharges molecules to larger cationic molecules.
Small are less affected compared to large
State the function of penetration enhancers.
Alter the epithelium structure to temporarily increase permeability
What does a typical nasal liquid formulation contain?
– API
– Antimicrobial preservatives (e.g. benzalkonium chloride)
– Antioxidants (e.g. butylated hydroxytoluene)
– Solubilising agents or co-solvents (e.g. glycol derivatives)
– Salts for adjusting pH and tonicity
– Humectants, to minimize irritation to the nose (e.g.
glycerol)
– Viscosity-enhancing agents (e.g. methylcellulose)
– Absorption enhancers
What drug treatments are used for the ear?
- Antibiotics
- Anti-inflammatories
- Antiseptics
- Cleansing solutions
- Wax softeners
What are the dosage forms available for the ear?
- Drops
- Sprays
- Washes
What is ear wax?
A normal bodily secretion which provides a
protective film on the meatal skin.
When does ear wax need to be removed?
if it causes deafness or interferes with a proper view of the ear drum.
What is ear wax composed of?
mostly lipophilic substances e.g. keratin, lipids, peptides, fatty acids, cholesterol.
What are cerumenolytics?
They soften the cerumen and lubricate the canal, thus facilitating ear wax removal from the ear canal
or by disintegrating it.
What is otitis externa?
- Inflammatory reaction of the meatal skin.
What is otitis externa caused by?
Bacteria or fungus
How can otitis externa be treated?
- Thorough cleaning of the ear canal by suction or dry mopping
- Corticosteroid ear drops, astringent solution or acetic acid
solution can be used.
What are astringent preparations?
A substance that causes shrinking or constriction of body tissues, usually locally after topical medicinal application.
