Booklet 9: Routes of Admin 2

Question 1

What is the buccal and sublingual route?

Answer 1

Administration via oral cavity drugs are placed under the tongue or retained in the mouth

Question 2

What is the purpose of the buccal and sublingual route?

Answer 2

Provides route for systemic administration which avoids exposure to the GI tract and liver

• most area well perfused with blood
• oral mucusa is a barrier so not highly permeable
• most substances absorbed by simple diffusion
• log P 1.6-3.3 optimal

Question 3

What are the advantages of the buccal route?

Answer 3

1. Avoids first pass effect
2. Abundance of blood vessel
3. Less hostile environment than the GIT
4. Fast cellular recovery
5. Directly and easily modify microenvironment
6. Lower intersubject variability as compared with transdermal patches
7. For drugs extensively metabolised in liver or unstable in the GIT
8. No stratum corneum
9. Can achieve sustained release

Question 4

What are the disadvantages of the buccal route?

Answer 4

1. Small absorption surface area
2. Movement affects mucoadhesive systems
3. Less permeable than the small intestine
4. Salivation and swallowing
5. Drug can’t be masked

Question 5

Applications for buccal delivery

Answer 5

1. Treat local and systemic conditions (eg. deliver Trinitrin for local treatment such as sore throat and other buccal infections
2. Delivery of large, hydrophilic and unstable proteins, oligonucleotides and polysaccharide
3. Alternative route for insulin delivery

Question 6

Anatomy and physiology of the nose

Answer 6

For smelling

• ofactory membrane approx 5% of total nasal area
• heats and humidifies inspired air
• 2 mucus layers 5-20mm thick
• surface pH of mucosal cells: 7.39
• mucous layer pH: 5.5-6.5
• back 2/3 covered with cilia -> mucociliary clearance
• facilitate movement mucus from nasal cavity to the nasopharynx

Question 7

3 classes of nasal delivery drugs

Answer 7

1. Alleviation of nasal symptoms
2. Alternative to injection for drugs inactivated by the GIT
3. Vaccines, peptides, insulin, interferon, buserelin, nafarelin

Question 8

Advantages of nasal delivery

Answer 8

1. Avoids hepatic first pass metabolism
2. Extremely rapid absorption, so only short exposure time for enzymatic activity to take place
3. Level of enzymes in the tissue low, can easily saturate with the drug

Question 9

Ideal properties of drug candidate

Answer 9

1. Appropriate aq solubility to provide desired dose per nostril
2. Low molecular weight (smaller better, cut off 20000 Da)
3. Low dose (<25mg/dose)
4. No nasal irritation
5. No toxic nasal metabolites
6. No offensive odors
7. Suitable stability

Question 10

Ideal nasal absorption enhancers

Answer 10

1. Increase absorption if drug
2. Not cause permanent damage or alteration to the tissues
3. Should not be irritant or toxic, either to local or rest of body
4. Be effective in small quantities
5. Enhancing effect should be temporary and reversible
6. Should be stable and compatible

Question 11

Types of parenteral drug administration

Answer 11

1. Intradermal
2. Subcutaneous
3. Intravenous
4. Intramuscular

Question 12

Intravenous admin

Answer 12

1. Immediate total access to bloodstream
2. Max conc reached in approx 4 mins
3. Duration of action depends on dose, timescale of admin (bolus or infusion) and distribution, metabolism and excretion
4. Large or small volumes can be given

Question 13

Intramuscular admin

Answer 13

1. Weak electrolytes: increased absorption w increased lipophilicity, may be binding to muscle protein
2. Hydrophilic neutral compounds
   - disperse from IM sites according to size
   - diffuse through muscle fibres through pores of capillary walls to blood
   - Pores only account for 1% of available surface of the capillary wall
   - Transport through capillary wall is the rate limiting step

Question 14

Subcutaneous admin

Answer 14

1. Dissolution and absorption phases occur slower than IM as blood supply is not good
2. Greater patient to patient variation in time to Cmax
3. Max volume approx 1mL
   Eg. Insulin, adrenalin

Question 15

Intrathecal drug admin (inserted into area under spinal cord)

Answer 15

Admin of drugs in solution by intrathecal catheter

• > drugs to brain and spinal cord
• more invasive than IV, IM or SC
• implanted catheters and pumps have been used to reduce risk of infection on repeated puncture

Question 16

Rectal drug delivery: advantages and disadvantages

Answer 16

• local effect
• systemic effect: when patients cannot use oral route, not stable, pH, drug not suitable for oral
• avoidance of first pass

Disadvantages: aversion (nationality dependent), slow and sometimes incomplete absorption, considerable inter- and intra- subject variation

Question 17

Anatomy and physiology of rectum

Answer 17

1. Last 150-200mm of the GIT
2. Essentially hallow, flat wall surface
3. Rectal mucosa normal lipoidal barrier, total surface area approx 300cm2
4. Mucous volume approx 3mL
5. Mucous pH approx 7.5, little buffering capacity
6. 3 systemic veins -> direct to circulation
7. No esterase or peptidase activity
8. No active transport mechanisms

Question 18

How does rectal absorption occur?

Answer 18

1. Drug molecules enter general circulation directly (lower and middle veins) or via liver (upper vein)
2. Avoidance of first pass is possible but the extent will depend on site of absorption
3. Depending on vehicle, a suppository will either dissolve in rectal fluid or melt on mucous layer

Question 19

Vaginal drug delivery

Answer 19

• Generally for local effects
• Can achieve systemic absorption
• > drug enters systemic system and avoids first pass
• > wide network of blood vessels
  eg. steroids, prostaglandins, some antibiotics

Question 20

How does vaginal absorption occur?

Answer 20

1. Epithelial layer increases in thickness after puberty and menopause
2. SA increased by folds and microridges
3. pH decreases after puberty to 4-5
4. Little fluid in the vagina
5. Absorption tends to be variable
6. Dosage from : pessaries

Question 21

Pulmonary drug delivert

Answer 21

• treatment or prophylaxis of airways diseases : asthma and cystic fibrosis
• rapid onset of activity for local action
• smaller doses can be administered for oral and parenteral routes
• useful where drug is poorly absorbed orally
  Systemic: large SA, abundance of capillaries

Question 22

Advantages of pulmonary drug delivery

Answer 22

1. direct admin to site of action
2. smaller quantities of drug required
3. rapid onset of action
4. reduced side effects

Question 23

Disadvantages of pulmonary drug delivery

Answer 23

1. seeking to defeat natural body defense
2. demands on patient (educated)
3. deposition is technically inefficient