Aural And Nasal Flashcards
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.
• Could achieve better systemic bioavailability than the oral
route:
Describe the nasal anatomy
- nasal cavity split in to 2 halves by nasal septum
- Covered with mucous membrane containing
goblet cells secreting mucus. - Absorption occurs across turbinates and septum
How are lipophilic and polar drugs transported across the nasal epithelium?
- Lipophilic Drugs: Transported transcellularly via:
• Passive diffusion (concentration-dependent)
• Receptor/carrier-mediated transport
• Vesicular transport mechanisms - Polar Drugs: Pass through epithelial tight junctions (paracellular pathway)
• Limited by molecular size (<1000 Da for effective transport)
What are the key functions of the nose in air filtration and drug delivery ?
• Functions of the Nose = passageway for air to the respiratory tract , Humidifies and warms incoming air
• Large particles trapped in nasal filter undergo rapid clearance
• Particles deposited on mucus are moved by ciliated epithelial cells toward the pharynx
• Site of particle deposition and clearance rate are crucial for local and systemic drug delivery
What is the function of the clearance system ?
• The function of this clearance system is to remove foreign substances from the nasal cavity, and this includes drugs.
What is local drug delivery ?
- Deliver directly at site of action
- rapid relief at lower dose compared to oral
- reduce systemic side effects
- eg. Nasal corticosteroids (reduces nasal mucosa
inflammation)
Why is intranasal delivery useful for systemic drug delivery, and what are some examples?
- Provides rapid onset of action, useful in emergencies.
- Bypasses first-pass metabolism, leading to faster drug absorption.
- eg. Fentanyl: Provides quick pain relief.
- The nasal delivery is effective but has low bioavailability.
How does solubility affect systemic 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.
What is mucociliary clearance, and why is it important in drug delivery ?
• Cilia found on the surface of epithelial cells transport mucus 5 mm per min toward the nasopharynx.
• function = remove foreign substances from the nasal cavity, and this includes drugs
How can solubility issues be overcome to improve absorption ?
- formulating as a suspension or powder in micro-size range, requires drug to dissolve in nasal cavity fluid before absorption
- select a different salt form of an ionisable drug
- use appropriate excipients eg.co-solvents
- modifying its molecular form (eg. prodrug )
How do lipophilicity and hydrophilicity affect systemic absorption via the nasal route?
- Lipophilic drugs are rapidly absorbed by transcellular route with bioavailability similar to that of IV. E.g. fentanyl, progesterone, propranolol.
- Hydrophilic drugs are absorbed via the paracellular route (between cells) and this route provided a much smaller area for absorption
How does molecular size affect absorption ?
- rate and extent of absorption is inversely proportional to the molecular weight of drug
- drugs with molecular mass <1 kDa have relatively efficient absorption.
- Particle size of 10-50 microns adheres best to the nasal mucosa.
how does degree of ionisation affect absorption ?
- Nasal mucosa surface has pH of 7.4, whilst mucus has a pH pf 5.5-6.5.
- Local pH becomes alkaline in certain nasal conditions e.g. acute rhinitis and acute sinusitis.
- Formulation pH closest to the nasal mucosa minimises local irritation, but pH 3-10 can be tolerated.
- Unionised drug molecules with a higher LogP (lipophilicity )better absorbed than ionized form.
how does enzymatic activity affect absorption ?
- enzymes in the nasal cavity are including monooxygenase, cytochrome P450, proteolytic enzymes
- drugs may be metabolised in the lumen or as they pass epithelium by enzymes
- so solution is to include enzyme inhibitors in formulation
- encapsulate drug - limits enzyme access
- use of prodrugs to reduce the affinity of drug for the enzyme
how does mucosal contact time affect absorption ?
- Increase residence time of drug in turbinates could potentially increase drug absorption.
- Mucoadhesive polymers (e.g. chitosan) can prolong the drug in contact with the mucosa without being absorbed themselves
- Increase formulation viscosity increases residence time
- increase contact time does not necessarily increase absorption
how does nasal epithelium permeability affect absorption ?
- The mucus layer is a diffusion barrier.
- permeability of small, uncharged molecules less affected by mucus layer compared to large, cationic, hydrophobic molecules.
- Penetration enhancers can be added to alter the epithelium structure temporarily to increase permeability.
what does the typical nasal liquid formation 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 (if necessary)
what are the advantages and disadvantages of nasal dropper/squeezed plastic bottle ?
- adv = cheap and simple systems for nasal delivery.
disadvantages: - Require considerable skill, dexterity and flexibility to apply the liquid uniformly across the mucosa.
– Require semi-recumbent or other unusual position. - The liquid delivered too quickly causes formulation to drip
from the nostril to throat, causing cough. - Volume administered is subject to patient technique. Only suitable for drugs with
large therapeutic window.
What are the key features and characteristics of nasal spray devices?
- solution and suspension can be formulated, in metered-dose pump or pre-filled syringe
- deliver exact dose from 25-200μl and spread across nasal mucosa.
- Easier and faster to administer than drops,
but requires priming.
What are the key characteristics and limitations of nasal tube devices for drug delivery?
- For creams, gels and ointments for local effects.
limitations: - Messy to apply, applied with finger or cotton bud.
- Uncontrolled dose.
what are the key characteristics + considerations for ear drops ?
- Used topically
- drug either in solution or suspension with a suitable vehicle (water, glycerol)
considerations: - Some vehicles (e.g. alcohol) may cause mild stinging
- Avoid products with nut oils (e.g., almond, peanut) in patients with nut allergies
- Oil-based preparations may need pre-warming with minimial heat to be more effective
what is ear wax + its composition + when does it need to be removed ?
- ear wax is normal bodily secretion which provides a protective film on the meatal skin.
- needs only be removed if it causes deafness or interferes with a proper view of the ear drum
- Composition of ear wax is mostly lipophilic substances ( keratin, lipids, peptides, fatty acids, cholesterol )
What are cerumenolytics, how do they work, and what are some common examples?
- agents that soften cerumen (ear wax) and lubricate the ear canal, so disintergrate or remove ear wax
- Common cerumenolytics: eg. olive or almond oil ear drops, waxsol, exterol
What is otitis externa, its causes, and treatment options?
- Inflammatory reaction of the meatal skin
- Mostly caused by bacteria or fungus.
- Many cases recover after thorough cleansing of the external ear canal by suction or dry mopping.
- Corticosteroid ear drops, astringent solution or acetic acid solution can be used.
What are astringent preparations, and example of how they’re used in ear treatments?
- substance that causes shrinking or
constriction of body tissues, usually locally after topical medicinal application - eg. Aluminium acetate ear drops (13 %)
What are the key components of corticosteroid ear preparations, and what is an example?
- formulated in combination with anti-infective drugs
- eg. Otomize® ear spray:
– Dexamethasone 0.1 % (corticosteroid)
– Nyomicin sulphate 0.6 % (antibiotic)
– Acetic acid 2 % (bactericide & fungicide)
– Water (solvent)
– Methyl hydroxybenzoate (preservative)
– Propyl hydroxybenzoate (preservative)
– Stearyl alcohol (viscosity enhancer)
acetic acid use + preparations + shelf life ?
- Acetic acid 2% can be used locally to treat mild otitis externa
- Possess antibacterial and antifungal activities, active against: Haemophilus and Pseudomonas species, Candida and Trichomonas
- Shelf life 18 months, then one month after first use.
