L32 - absorption: sublingual, buccal & rectal drug delivery Flashcards
is contact of most drugs with oral cavity brief?
yes as most drugs are swallowed
what is topical drug delivery to mouth used for?
ulcers, functor infections, periodontal disease
2 types of oral transmucosal delivery
- sublingual: under tongue
- buccal: cheeks
what is the lining of the oral cavity?
oral mucosa (buccal, sublingual, gingival, labial, palatal mucosae)
what is gingival?
gums
SA of buccal + sublingual
~ 200cm cubed
- smaller than SI
structure of oral mucosa
- stratified squamous epithelium in cell
2.lamina propria: contains blood vessels + nerve endings, so we need to get drug past this into systemic circulation. - basement memb + cells above = spread out as they age
- prickle cells = lipophillic membrane coating granules, affects absorption of drugs
3 types of epithelium in mouth
- masticatory: gums + palatal
- lining: buccal + sublingual
- specialised: dorsal tongue
structure of masticator mucosal epithelium (gingival + palatal)
layer of keratin on outer layer of cells acts as barrier to drug absorption, so poor permeability
- good residence time of palatal = sticks very well to it
- gums have intermediate residence time
structure of lining epithelium?
no layer of keratin.
- sublingual memb thinner so better permeability, bad residence time
- buccal has intermediate residence time
permeability of masticatory epithelium
poor
permeability of lining epithelium
buccal = intermediate
sublingual = very good
what pathway do lipophilic drugs pass through?
most common transceullar pathway via passive diffusion.
- rate of drug absorption affected by epithelial thickness
what pathway do hydrophilic drugs pass through?
- paracellular (more common in MOUTH).
- due to intracellular lipids from memb coating granules
- epithelial thickness effects rate of drug absorption across memb
order of permeability
skin < oral mucosa < GI
what is the pH of oral cavity?
5.6-7.6 = small area + small volume of liquid in mouth so not much space for buffering
log P values of drugs via oral membranes
generally 1-5
what is saliva?
95% water + mucus, electrolytes, enzymes
why do we need saliva for drugs?
for drug to go in solution to be absorbed
enzymes in saliva
aminopeptidases, carboxypeptidases, esterases, carbohydrases (e.g amylase), lysozyme: fewer enzymes and lower activity than GI tract
what can saliva do to drug absorption?
- can aid or hinder it when drug is being deliver sublingually
- saliva wash otu
what is mucus for drugs?
- physical barrier
- negatively charged so can hinder absorption of positively charged drugs
blood supply in mouth
good blood flow
how does the buccal and sublingual route avoid hepatic first pass effect?
drug can go straight into systemic circulation
oral transmucosal insulin delivery
- insulin
- surfactant
- solubilizer
- micelle-creating agent
- emulsifying agents
features and benefits of oral transmucosal insulin delivery
- needle free, pain free tech (non invasive)
- rapid onset of action
- no lung deposition (absorption in the buccal mucosa)
- FDA approved excipients
- precise dose control
- expected improvement in compliance
- easy self administration
- convenient to carry and handle
advantages of oral transmucosal insulin delivery
- accessible + easy to deliver
- large SA
- rich blood supply
- low metabolism
- avoidance of hepatic first pass
- low variability
- prolonged contact
- alt to oral delivery
disadvantages of oral transmucosal insulin delivery
- high MW drugs have to be potent
- adverse reactions
- saliva + mucus
- acceptance
- development cost
real drug administration
for local effects
who is rectal drug administration a good route for?
- unconscious patiens
- children
- ppl who are vomiting
- patients with upper gi tract disease
- drugs with bad taste
- drugs that degrease via oral delivery
rectal dosage forms
- suppositries
- capsules
- tablets
- ointments, creams, gels
- solutions, emulsions & suspensions
rectal anatomy
- normally empty
- 3ml mucus
- pH ~7.5, little buffering capacity
is rectal a possible route for protein delivery?
yes as non esterase or peptidase activity
rectal blood supply
- highly vascularised
- venous drainage
- superior vein empties into hepatic vein into liver
- inferior goes into systemic cirucltuon
- can avoid first pass effect
- complicated by BV linked together (anastomoses)
first pass avoidance - diazepam gel
- diazepam metabolised to active metabolite by CYP in liver
- diazepam rectal gel for refractory epileptic patients
- controls seizure activity
rectal gel adminsitation
- low incidence for respiratory depression
- low potential for abuse
- no healthcare profesional needed
- overdose is rare
advantages of rectal administration
- safe, painless
- no degradation in gi
3, no hepatic first pass - good range of dosages possible
- extended absorption
- protein delivery
disadvantages of rectal administration
- acceptability
- upwards movement leads to hepatic first pass
- insertion issues
- slow absorption
- leakage
