L9: ENT/dental delivery systems Flashcards
What is the anatomy of the ENT and oral passage?
Interconnected series of mucosal tissues
- Eardrums, nostrils, lips, oesosophagus (after this no longer mucosal)
Links ears, nose, tongue
Particulate matter is cleared by expulsion or swallowing
Is the outer ear mucosal?
NO - epithelium, protected by cerumen (earwax)
What are some indications for outer ear preparations?
Only for local use in outer ear
- Earwax removal, anti-infective, anti-inflammatory, analgesic
What excipients are in outer ear solutions?
Water
Ethanol –> highly volatile & will evaporate quickly, taking excess fluid with it and leaving drug behind in the ear
More viscous solvents –> to allow drug to stay in ear canal for longer, but make it harder for earwax to come out –> depends on indication ie. antibiotics vs earwax removal
- Glycerin
- Propylene glycol
What are the characteristics of the eardrum & what does it mean for some formulations?
Water-tight, air-tight barrier
- Eardrops cannot permeate through tissue
- Injections rarely performed, in operation setting
- -> Systemic/oral formulations most appropriate
What are the paranasal sinuses?
Paired cavities connected to ENT system
How to treat local infections?
NASAL IRRIGATION to treat locally
- Drain mucous from nasal/sinus passages (salt rinses)
- Can reach all connected sinuses & Eustachian tube
Nasal mucosa - characteristics
Rich blood supply into systemic circuit
Access to nervous system –> can get straight into cerebrospinal fluid
Drugs delivery can be local, systemic, brain-targeted
What is the relationship between mucous & mucosa?
Mucous
- Viscous aqueous discharge ON TOP of mucosal epithelial surfaces
- Drugs must be able to permeate through this & not be cleared out
Mucosa
- Epithelial surfaces COATED with mucous
- Important barrier function
How can drugs deposit in the nose?
To ensure droplets remain in the nose & are not inhaled into the lungs (5-10 micrometre) –> particle size should be 30-120 micrometre
How is drug droplet size controlled?
Vapour pressure –> higher = smaller size
Drug particle diameter –> aerosol diameter will also be larger since it has to coat drug particle
Actuator nozzle diameter (mesh bit)
Drug concentration –> increased size can aggregate & make ‘bigger’ particles
Nasal delivery systems need to have properties of…
MUCOPENETRATION
- Ability to freely move around MUCOUS fluid
MUCOADHESION
- Ability to form intermolecular interactions and stick to MUCOSAL membrane
–> to prevent getting cleared by ciliary processes in the nose
How is mucopenetration achieved?
Easier for small, uncharged particles
How is mucoadhesion achieved? (what types of excipients must be contained?)
Effectively wet & spread around the mucosa
Interact with mucosal glycoproteins (so that mucoadhesion can take place)
- van der Waals preferred over ionic –> hydrophobic. fits with small uncharged properties of the particle in mucopenetration
eg. PEG –> neutrally charged particles –> able to move more freely in mucous; mucopenetration increases.
What are ideal properties for systemic drugs delivered through nasal mucosa?
Molecular weight –> <500Da
Moecular shape –> globular
pKa –> non-ionised at nasal pH 5.5-6.3, 8.3 in rhinitis
logP –> <5
Solubility –> in suspension, should rapidly dissolve in mucous
What are common nasal formulations?
Liquids, sometimes semi-solids, rarely powders
Sprays optimal –> can reach deeper into nose but can only administer non-viscous solutions
Drops convenient but no dose precision
Nasal formulation excipients to adjust
Osmolarity –> hyperosmotic irritant to mucosa
Viscosity –> more viscous can retain at site of action for longer
Drug solubility –> needs to be dissolve to be absorbed. also, may not have a long time in nose to dissolve then be absorbed, so cut down one step first
Formulation pH –> as close to nasal pH to be non-irritating
How do nasal formulations reach the brain?
Olfactory bulb –> goes to CSF & brain
Trigeminal nerve –> goes to brain
Common formulations for laryngeal/pharyngeal administration?
Gargles
Throat sprays
Lozenges
Gums
–> hard to get prolonged effect due to constant swallowing
Dental drug delivery
Toothpaste
- Fluoride
- Abrasives –> remove plaque off teeth
- Flavours
- Humectants –> retain moisture in formulation
- Detergents –> foaming when brushing teeth, easier for fluoride to reach more places
Mouthwash
Gingival depots
Placed between tooth and gum
Slow release of doxycycline over 21 days
Dental sponges
Geletamp
- Sponge inserted into tooth scket after extraction
- Porous structure that absorbs blood –> promote thrombocyte aggregation, stabilise coagulum
- Prevents infections entering site
- Resorbed in 4 weeks
Oromucosal drug delivery
Good wetting & mucoadhesion –> lots of movement in mouth
Systemic drug delivery through mouth
Sublingual eg. GTN
Buccal eg. prochlorperazine
–> fast absorption due to thin membrane, short distance to bloodstream
What are SIX advantages of oromucosal systemic delivery?
Easy to administer Avoid first-pass metabolism Avoid gastric environment Little dose variation Rapid onset of action (sublingual) Sustained delivery possible (buccal)
What are FIVE disadvantages of oromucosal systemic delivery?
Small surface area limits drug dose
Bitter/nauseating drugs not tolerated since so close to tongue
Drug needs to be stable at salivary pH
Dissolution of drug in saliva can result in swallowing –> this becomes oral administration
Only absorbed by passive diffusion (small, unionised, lipophilic)
