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
What are examples of buccal dosage forms?
- conventional buccal tablets and capsules
- adhesive delivery systems
- chewing gums
What are the problems with using conventional systems in the buccal route?
- stimulate salivation
- drug solution may be drained
- poor retention at site
- discourages speaking and drinking
What is bioadhesion?
-binding of natural or synthetic polymer to biological substrate
What is mucoadhesion?
binding of natural or synthetic polymer to a mucosa membrane
What is the benefit of bioadhesion and mucoadhesion?
-increased retention time at the site of absorption
What are advantages of mucoadhesion in buccal drug delivery?
- increases contact time
- localisation
- potential for SR (can be designed to stick to buccal membrane for up to 6 hours)
- avoids metabolising enzymes
- does not interfere with patient activities although patient acceptability can vary
What are the theories to mucoadhesion?
- wettability theory
- electronic theory
- adsorption theory
- diffusion interlocking theory
What is the wettabiltiy theory?
mucoadhesion is to do with the contact angle/spreadability of the polymer onto the surface of the mucosa membrane
What is the electronic theory?
mucoadhesion occurs as a result of attraction resulting from electron transfer
What is the adsorption theory?
mucoadhesion occurs due to ionic, covalent, metallic bonding or VDW interactions
What is the diffusion interlocking theory?
mucoadhesion occurs as particles of the mucoadhesive diffuse through the membrane and interolock with particles of the membrane
What other tests (aside from drug release and dissolution profiles) can help to measure mucoadhesion in vito?
- force of attachment
- rheological measurement
What mucous is used in the characterisation of mucoadhesive drugs?
- commerically dried mucous.
- this is rehydrated before testing
What in vivo tests can be done on mucoadhesive drugs?
-GI transit time
What are the three main classifications of bioadhesive polymers?
- synthetic
- natural
- semi-synthetic cellulose derivative
What are examples of synthetic bioadhesive polymers?
- polyacrylic acid
- polymethacrylate
What are examples of natural bioadhesive polymers?
- pectin
- chitosan
- xanthan gum
What are examples of semisynthetic, cellulose derived bioadhesive polymers?
- HPMC (hyroxypropylmethyl cellulose)
- HPC (hydroxypropyl cellulose)
- HEC (hydroxyethyl cellulose)
- SCMC (sodium carboxymethyl cellulose)
What are the two main classes of factors that affect bioadhesion?
- polymer related factors
- environment related factors
What are the polymer related factors that affect bioadhesion?
- MW, chain length, conformation
- functional groups
- pH/charge
- concentration of polymer
- level of hydration
What are the environment related factors that affect bioadhesion?
- pH of environment
- application force
- contact time
What is BUCCASTEM M?
-buccal tablet used to treat nausea and vomiting assoc with migraines
What does BUCCASTEM M contain?
- each tablet contains prochlorperazine 3mg
- other ingredients include sugar, povidone K30, xanthan gum, locust bean gum, talc, magnesium stearate and riboflavin sodium phosphate
How is BUCCASTEM M administered?
-in the buccal cavity between upper lip and top gum
