L32 - Absorption: Sublingual, Buccal And Rectal Drug Delivery Flashcards
What is topical drug delivery to the mouth used to treat? (3)
- ulcers
- fungal infections
- periodontal disease
What are the different transmucosal delivery? (2)
- sublingual
- buccal
What has a signigicant effect on drug absorption?
They physiology of the mouth
What is the lining of the mouth?
Oral mucosa
(Buccal, sublingual, gingival, labial, palatal mucosae)
200cm2 (buccal + sublingual)
What is the structure of the oral mucosa? (4)
- epithelium (membrane coating granules from prickle cells)
- basement membrane
- lamina propria
- sub-mucosa
What are the different mucosal types? (3)
- masticatory (gingival, palatal tissue)
- lining (buccal, sublingual tissue)
- specialsied (dorsal tongue)
What is the structure, thickness (mcm), permeability, residence time and % area of masticatory gingival tissue? (5)
- K
- 200mcm
- poor
- intermediate
- 50%
What is the structure, thickness (mcm), permeability, residence time and % area of masticatory palatal tissue? (5)
- K
- 250mcm
- poor
- very good
- 50%
What is the structure, thickness (mcm), permeability, residence time and % area of lining buccal tissue? (5)
- NK
- 500-600
- intermediate
- intermediate
- 30&
What is the structure, thickness (mcm), permeability, residence time and % area of lining sublingual tissue?
- NK
- 100-200
- very good
- poor
- 30%
What is the structure, thickness (mcm), permeability, residence time and % area of specialised dorsal tongue tissue?
- K/NK
- n/a
- n/a
- 20%
What goes through transcellularly?
Small lipophilic drugs
- passive diffusion, epithelial thickness affects flux
What goes through paracellularly?
Small hydrophilic drugs
- epithelial thickness affects flux
- intracellular lipids (MCGs)
What is the pH of oral cavity?
Approx 5.6-7.6
Log P values generally 1-5
What is saliva composed of?
Water + mucus, electrolytes and enzymes
- 0.5-2.0 L per day, 1.1 mL present
What are degraders in the saliva? (5)
- Aminopeptidases,
- carboxypeptidases
- esterases
- carbohydrases
- lysosymes
What is saliva wash out?
Aid or hinder drug asborption
What type of barrier is mucus? (2)
- physical (30.400mcm)
- chemical (-ve charge)
What is blood supply like in the mouth? (2)
- good blood fow (Buccal = 2.4 ml min-1 cm-2, Sub-lingual = 0.97 ml min-1 cm-2)
- Avoids hepatic first-pass metabolism
What are other factors that affect oral delivery? (4)
- residence time
- taste
- irritation
- compliance
What is the bioavailability of subingual nitroglycerin?
38%
- rapidly absorbed sublingually
What happens to sublingual nitroglycerin?
trinitroglycerine to dinitroglycerin to monoglycerine to glycerine
What are alternative administration routes of the buccal testosterone delivery? (4)
- oral
- IM
- SC implant
- dermal (patches or gel)
Controlled drug delivery system
What is buccal testosterone delivery like? (2)
- well tolerated for long-terms use
- common adverse events are local irritation and dysgeusia
What are traditional treatment of BCP of opioid delivery? (2)
- background analgesia
- typical breakthrough pain episode before treatment with normal release opioid
What are treatment with quick onset and short duration of BCP of opioid delivery? (2)
- background analgesia
- treat with ideal rescue medicine during typical breakthrough pain episode
What is the opiod delivery of buprenorphine? (3)
- outpatient treatment of opiod addiction
- as effective as methadone, generally safe and well-tolerated
- once daily sublingual tablet
What is the oral transmucosal insulin delivery composed of? (6)
- insulin
- surfactant
- solubiliser
- micelle-creating agent
- emulsifying agent
- [all exceipient found on the FDA GRAS list]
What are features of transmucosal insulin delivery? (8)
- Needle-free
- Rapid onset of action
- No lung deposition (absorption in the buccal mucosa)
- Established safety profile (FDA approved excipients)
- Precise dose control (meets USP guideline)
- Expected Improvement in Compliance
- Easy self-administration
- Convenient to carry and handle
What are advantages of sublingual/buccal delivery? (8)
- access and ease
- large SA
- rich blood supply
- low metabolism
- avoids hepatic first pass
- low variability
- prolonged contact
- alternative to oral delivery
What are disadvantages of sublingual/buccal delivery? (5)
- high MW drugs must be potent
- adverse reactoins
- saliva & mucus
- acceptance
- development cost
What is the rectal drug administration an excellent route of drug delivery for? (6)
- Unconscious patients
- Children
- Patients that are nauseous/vomiting
- Patients with upper GI tract disease
- Drugs with an objectionable taste
- Drugs extensively degraded via oral delivery
What are rectal dosage forms? (5)
- suppositories
- capsules
- tablets
- ointments, creams & gels
- solution, emulsions & suspensions
What is the rectal anatomy? (6)
- Last 15-20 cm of the colon
- Upper and lower regions
- ~300 cm2 (no villi)
- Normally empty
- ~3 ml mucus
- pH ~7.5 - little buffering capacity
What is transcellular and paracellular absorption dependent on? (4)
- size
- lipophilicity
- ionisation
- simple epithelium
What is rectal delivery like? (3)
- sustained release and absorption possible
- metabolism of some drugs by bacteria
- no esterase/peptidase activity - possible route for protein delivery
What is the rectal blood supply like? (4)
- highly vascularised
- venous drainage (inferior & middle veins, lower) (superior vein, upper)
- avoids hepatic first pass
- complicated by anastomoses
What is the first pass avoidance of diazepam gel?
- metabolised to desmethyldiazepam (major metabolite; active) by CYP2C19 and CYP3A4 in liver (two minor active metabolites)
What is diazepam gel who for and what for? (2)
- management of selected, refractory epileptic patients
- used to control bouts of increased seizure activity
What are advantages of diazepam gel? (5)
- Very low incidence of respiratory depression
- Low potential for abuse
- Does not require trained healthcare professional to administer injection
- Serious consequences from overdose of rectal gel are rare
- However, under-administration may be an issue (failure to control seizures)
What are advantages of rectal delivery? (7)
- safe and painless
- avoids degradation in GI tract
- avoids hepatic first pass
- good range of dosages possible
- potential extended absorption
- good alt in certain patient groups
- potential for protein delivery
What are disadvantages of rectal delivery? (5)
- acceptability (long term)
- upwards movement leads to hepatic first pass
- insertion issues
- slow absorption (compared to oral and iv)
- leakage
