L32 - absorption: sublingual, buccal & rectal drug delivery

Question 1

is contact of most drugs with oral cavity brief?

Answer 1

yes as most drugs are swallowed

Question 1

what is topical drug delivery to mouth used for?

Answer 1

ulcers, functor infections, periodontal disease

Question 2

2 types of oral transmucosal delivery

Answer 2

1. sublingual: under tongue
2. buccal: cheeks

Question 3

what is the lining of the oral cavity?

Answer 3

oral mucosa (buccal, sublingual, gingival, labial, palatal mucosae)

Question 4

what is gingival?

Answer 4

gums

Question 5

SA of buccal + sublingual

Answer 5

~ 200cm cubed
- smaller than SI

Question 6

structure of oral mucosa

Answer 6

1. stratified squamous epithelium in cell
   2.lamina propria: contains blood vessels + nerve endings, so we need to get drug past this into systemic circulation.
2. basement memb + cells above = spread out as they age
3. prickle cells = lipophillic membrane coating granules, affects absorption of drugs

Question 7

3 types of epithelium in mouth

Answer 7

1. masticatory: gums + palatal
2. lining: buccal + sublingual
3. specialised: dorsal tongue

Question 8

structure of masticator mucosal epithelium (gingival + palatal)

Answer 8

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

Question 9

structure of lining epithelium?

Answer 9

no layer of keratin.
- sublingual memb thinner so better permeability, bad residence time
- buccal has intermediate residence time

Question 10

permeability of masticatory epithelium

Answer 10

poor

Question 11

permeability of lining epithelium

Answer 11

buccal = intermediate
sublingual = very good

Question 12

what pathway do lipophilic drugs pass through?

Answer 12

most common transceullar pathway via passive diffusion.

• rate of drug absorption affected by epithelial thickness

Question 13

what pathway do hydrophilic drugs pass through?

Answer 13

• paracellular (more common in MOUTH).
• due to intracellular lipids from memb coating granules
• epithelial thickness effects rate of drug absorption across memb

Question 14

order of permeability

Answer 14

skin < oral mucosa < GI

Question 15

what is the pH of oral cavity?

Answer 15

5.6-7.6 = small area + small volume of liquid in mouth so not much space for buffering

Question 16

log P values of drugs via oral membranes

Answer 16

generally 1-5

Question 17

what is saliva?

Answer 17

95% water + mucus, electrolytes, enzymes

Question 18

why do we need saliva for drugs?

Answer 18

for drug to go in solution to be absorbed

Question 19

enzymes in saliva

Answer 19

aminopeptidases, carboxypeptidases, esterases, carbohydrases (e.g amylase), lysozyme: fewer enzymes and lower activity than GI tract

Question 20

what can saliva do to drug absorption?

Answer 20

• can aid or hinder it when drug is being deliver sublingually
• saliva wash otu

Question 21

what is mucus for drugs?

Answer 21

• physical barrier
• negatively charged so can hinder absorption of positively charged drugs

Question 22

blood supply in mouth

Answer 22

good blood flow

Question 23

how does the buccal and sublingual route avoid hepatic first pass effect?

Answer 23

drug can go straight into systemic circulation

Question 24

oral transmucosal insulin delivery

Answer 24

1. insulin 2. surfactant 3. solubilizer 4. micelle-creating agent 5. emulsifying agents

Question 25

features and benefits of oral transmucosal insulin delivery

Answer 25

1. needle free, pain free tech (non invasive) 2. rapid onset of action 3. no lung deposition (absorption in the buccal mucosa) 4. FDA approved excipients 5. precise dose control 6. expected improvement in compliance 7. easy self administration 8. convenient to carry and handle

Question 26

advantages of oral transmucosal insulin delivery

Answer 26

1. accessible + easy to deliver 2. large SA 3. rich blood supply 4. low metabolism 5. avoidance of hepatic first pass 6. low variability 7. prolonged contact 8. alt to oral delivery

Question 27

disadvantages of oral transmucosal insulin delivery

Answer 27

1. high MW drugs have to be potent 2. adverse reactions 3. saliva + mucus 4. acceptance 5. development cost

Question 28

real drug administration

Answer 28

for local effects

Question 29

who is rectal drug administration a good route for?

Answer 29

- unconscious patiens - children - ppl who are vomiting - patients with upper gi tract disease - drugs with bad taste - drugs that degrease via oral delivery

Question 30

rectal dosage forms

Answer 30

1. suppositries 2. capsules 3. tablets 4. ointments, creams, gels 5. solutions, emulsions & suspensions

Question 31

rectal anatomy

Answer 31

- normally empty - 3ml mucus - pH ~7.5, little buffering capacity

Question 32

is rectal a possible route for protein delivery?

Answer 32

yes as non esterase or peptidase activity

Question 33

rectal blood supply

Answer 33

- 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)

Question 34

first pass avoidance - diazepam gel

Answer 34

- diazepam metabolised to active metabolite by CYP in liver - diazepam rectal gel for refractory epileptic patients - controls seizure activity

Question 35

rectal gel adminsitation

Answer 35

1. low incidence for respiratory depression 2. low potential for abuse 3. no healthcare profesional needed 4. overdose is rare

Question 36

advantages of rectal administration

Answer 36

1. safe, painless 2. no degradation in gi 3, no hepatic first pass 4. good range of dosages possible 5. extended absorption 6. protein delivery

Question 37

disadvantages of rectal administration

Answer 37

1. acceptability 2. upwards movement leads to hepatic first pass 3. insertion issues 4. slow absorption 5. leakage