Oromucosal drug delivery Flashcards
What are examples of drugs delivered locally using the oral mucosa?
- lidocaine
- prostaglandin
- miconazole
What are examples of drugs delivered systmemically using the buccal route of the oral mucosa?
- insulin
- diltiazem
- bupoprion
What are examples of drugs delivered systemically using the sublingual route of the oral mucosa?
nitrates
Where is the buccal mucosa?
on the cheeks and gums in the mouth
Where is the sublingual mucosa?
under the tongue and the floor of the mouth
What is local oromucosal drug delivery used for?
- local anaesthetics,
- anti infectives
- antitussives
- lozenges, gels, gargles and throat sprays
What are lozenges?
a. k.a troches
- these are solid dosage forms formed using high pressure during tableting to yield slow release
- based on melted flavoured syrup vehicle.
- high sugar contents provide soothing effect
- developing dosage form for a number of other drugs such as sildenafil citrate
What is Atridox?
- a SR formulation of doxycycline hyclate 10% used for the treatment of periodontal disease
- provides slow release of doxycycline for up to 21 days
- systemic dosing
- dose required and has side effects
What is an example of an adhesive paste?
- oracort which is a mucoadhesive paste to treat mouth ulcers
- it has two functions:
1. barrier to speed up healing
2. anti-inflammatory as it contains the corticosteroid triamcinolone
What is an example of an adhesive gel?
- Bonjela
- contains choline salicylate
- contains lidocaine in the infant’s version, to treat teething
What are the layers of the oral mucosa?
- mucous/saliva
- superficial layer
- intermediate layer
- pickle cell layer
- basal layer
- basement membrane
- lamina propria
- submucosa
what are the main features of the oral mucosa anatomy?
- epithelium comprises stratified squamus cells
- buccal and sublingual areas are non-keratinised which facilitate rapid drug absorption
- sublingual permeation and absortpion rates are greater than for buccal
- buccal permeation rates are between those of the skin and intestine
Which route (buccal vs. sublingual) is more appropriate for rapid systemic absorption?
sublingual as it contains rapid permeation and absorption rates
it is also highly vasculated so drug will go into systemic circulation
Which route (buccal vs. subligual) is more appropriate for sustained release?
-buccal as it has a slower permeation rate.
How does the permeability barrier of the buccal and sublingual anatomy compare to that of the oral-GIT and the skin?
- buccal and sublingual both comprise of non-keratinised sqaumous epithelium
- oral-GIT = columnar eithelium
- skin = keratinocytes
How does the thickness in microns of buccal and sublingual anatomy compare to that of oral-GIT and skin?
- buccal: 500-800 (slower permeability)
- sublingual: 100-200
- oral GIT: 10-100
- Skin: 20-100
How does the biological environment of the buccal and sublingual anatomy compare to that of the oral-GIT and skin?
- buccal and sublingual: Saliva pH6
- oral-GIT: fluids, pH1-8
- skin: little aqueous media, pH 5
How does the barrier resistance of the buccal and sublingual anatomy compare to that of the oral-GIT and skin?
from order of least resistant:
- sublingual
- oral-git
- buccal
- skin
How does the the metabolic barrier of the buccal and sublingual anatomy compare to that of the oral-GIT and skin?
- buccal and sublingual: no metabolic barrier
- oral-GIT: liver, which has high metabolic barrier
- skin: low metabolic barrier.
What are the advantages of systemic delivery through the oromucosal route?
- easily accessible
- therapy can be terminated
- avoids FPM
- eliminates enzyme and acid mediated drug degradation
- localisation of drug and dosage form
- rapid onset of action which is useful for drugs like nitroglyercine
- presence of saliva is useful for dissolving formulations
- possibility of sustained release
- delivery of protein/peptide drugs
What are the limitations of systemic delivery through the oromucosa route?
- small surface area limits dose of drug
- drugs can’t be bitter/nauseous
- drug must be stable at saliva pH
- dissolution of drug in saliva can result in swallowing
- buccal mucosa is less permeable compared to other mucous membranes (rectum, intestine, vagina)
- only drugs absorbed by passive diffusion can be administered
What are the advantages specific to the sublingual route?
- accessible
- relatively permeable
- rapid absorption
- acceptable bioavailability
What are the specific advantages of the buccal route?
- mucous is more immobilised
- not washed with large amounts of saliva
- suitable for SR formulations
- potential for deliverying peptide drugs
What is the mechanism of drug absorption through the oromucosa?
- mainly passive diffusion
- depends on pKa of drug and pH of medium
- absorbed via diffusion
- absorption is proportional to initial concentration and time of contact
- absorption increases with increased unionised species
