Routes Of Administration (Aural & Nasal) Flashcards
What are the typical therapeutic areas for nasal drug delivery?
- Local delivery: nasal allergy, congestion infection
- systemic delivery
- vaccine delivery
- access to CNS
What are the advantages of the nasal route?
- Easy to administer
- non-invasive, painless
- avoids first-pass effect
- direct route to brain possible
- could achieve better systemic bioavailability than the oral route
What is the nasal anatomy?
- Nasal cavity is divided by 2 halves by nasal septum
- covered with mucus membrane containing goblet cells secreting
- absorption occurs across turbinates and septum
How do lipophilic drugs transport across nasal cavity?
- Transported transcellularly by concentration dependent passive diffusion, by receptor carrier mediated & vesicular transport mechanisms.
How do polar drugs pass through epithelium?
- Via gaps between cells. So limited to drug molecular size > 1000 da
What is the nose brain pathway?
- The olfactory mucosa is in direct contact with the brain & cerebral spinal fluid
- drug can absorb across olfactory mucosa & enter cns
- can bypass blood brain barrier = rapid
What are the functions of the nasal airway?
- Act as a passageway for the movement of air into the respiratory tract & an air conditioner to humidity warm the air
- Large particles trapped undergo rapid clearance and move towards pharynx
What are the benefits of using the nasal route to treat locally?
- Deliver directly at site of action
- Permit rapid relief at much lower dose
- Reduce systemic effects
What are the benefits of using the nasal route to treat systemically?
- Intranasal delivery where emergency situations and rapid action is required
- Nasal delivery of peptides has been successful although with low bioavailability (portion entering bloodstream)
What are factors affecting systemic absorption?
- Solubility
- Lipophilicity/ Hydrophilicity
- Molecular size
- Degree of ionisation
- Enzymatic activity
- Mucosal contact time
- Nasal epithelium permeability
How does solubility affect systemic absorption?
- Drug must be in solution to be absorbed
- Only 25-200ul can be administered intranasally
How can the problem of solubility in nasal route be overcome?
- As suspension or micro size powder, but requiring drug to dissolve first in nasal cavity before absorption
- Selection of different salt of an ionisable drug
- Excipients (co solvents)
- Modification of molecular form (pro drug)
How does lipophilicity or hydrophilicity affect systemic absorption?
- Lipophilic: rapidly absorbed from nasal cavity by transcellular route with bioavailability same as IV
- Hydrophilic: absorbed via paracellular route (between cells) and the route provides smaller area for absorption
How does Molecular Size affect systemic absorption
- The rate of absorption is inversely proportional to weight
- Particle size of 10-50 microns are best : Too small (pass onto lungs), Too big (run-out of nose)
How does Degree of Ionisation affect systemic absorption?
- Nasal mucosa has a pH of 7.4 whilst mucus has a pH of 5.5-6.5
- Formulation close to nasal mucosa minimises irritation
- Unionised drug with higher LogP (conc of drug in oil: conc of drug in aq) is better absorbed than ionised form
How does Enzymatic Activity affect systemic absorption?
- Broad range of enzymes are in the nasal cavity (mono oxygenases, cytochrome P450, proteolytic enzymes)
- Drugs may be metabolised in the lumen or pass across epithelium
- Some possible solutions: use enzyme inhibitors, use prodrugs, encapsulate drug
How does Mucosal contact time affect systemic absorption?
- Increase residence time of drug in turbinates (shell shaped networks of bone, vessels and tissue)
- Mucoadhesive polymers can prolong drug in contact with mucosa
- Increase formulation viscosity (increases residence time)
- However increasing contact time not necessarily increase absorption (rate of diffusion decreased due to high viscosity)
How does Nasal epithelium permeability affect systemic absorption?
- The mucus layer is a diffusion barrier
- Permeability of small, uncharged molecules are less affected compared to larger, cationic molecules
- Penetration enhancers can alter epithelium structure and increase permeability
What are the main components of nasal liquid formulation?
- API
- Antimicrobial preservatives
- Antioxidants
- Solubilising agents or co-solvents
- Salts (for adjusting pH and tonicity)
- Humectants (reduce irritation to nose)
- Viscosity-enhancing agents
- Absorption enhancers
What are the main nasal devices?
- Dropper/ squeezer: Cheap and flexible. Can apply liquid uniformly. Liquid delivered too quick (causes cough). Based on patient technique
- Nasal Spray: Both solution and suspension. Easier and faster to administer but requires priming (preparing before use)
- Nasal Tubes: Local effects for creams and gels. Messy to apply
What are the different drug treatments for the ear?
- Antibiotics
- Anti inflammatories
- Antiseptics
- Cleaning solutions
- Wax softeners
What are the different dosage forms available to be used for the ear?
- Drops: topical use, either solution or suspension, with suitable vehicle (water, glycerol)
- Sprays
- Washes
What is ear wax?
- Normal bodily secretion which provides a protective film on meatal skin
- Only removed if causes deafness or interferes with ear drum
- Composition of ear wax: mostly lipophilic (keratin, lipids, fatty acids, cholesterol)
What are Cerumenolytics?
- Acts by softening the cerumen and lubricating the canal, facilitating ear wax removal
- E.g: Olive or almond ear drops, sodium bicarbonate ear drops
What is the Otitis externa?
- Inflammatory reaction of the meatal skin
- Mostly caused by bacteria or fungus
- Many recover after cleansing of the external ear canal or dry mopping. Corticosteroid ear drops can be used
What are Astringent preparations?
- An astringent is a substance that causes shrinking or constriction of body tissues, usually locally after topical medicinal application.
- Aluminium acetate ear drops (13%)
What are corticosteroid preparations?
- Are often formulated in combination with anti-infective drugs
- Reduce inflammation and irritation to skin
What are Acetic Acid preparations?
- Acetic acid (2%) is used to treat mild otitis externa
- Possess antibacterial and antifungal activities
