Exam 3 (& new material) - Mucosal

Question 1

Define “mucoadhesion”

Answer 1

The state in which a material (polymer) and the mucus are held together for extended periods of time by interfacial forces

Question 2

Explain the role of mucoadhesion

Answer 2

Prolongs residence time of the dosage form on the mucosal surface

Question 3

Explain the PURPOSES of mucoadhesives

Answer 3

• Controlled release systems (extended/sustained release)
• Enhancement of poorly absorbed drug molecules
• Immobilization of the dosage form at the desired site of action

Question 4

Explain the MECHANISM of mucoadhesion

Answer 4

• Electrostatic interaction: positive charge of polymer vs negative charge of sialic acid in mucin
• Hydrogen bonding (e.g -COOH, -OH, -NH2)
• Covalent bonding: disulfide bond (S-S) between thiolated polymer and cysteine-rich portion of mucin
• Physical interpenetration

Question 5

List advantages of mucoadhesion

Answer 5

• Avoid the first pass effect (no metabolism in the liver)
• Drug absorbed into the reticulated and jugular veins, which is drained into the systemic circulation
• Non-invasive
• Relative ease and convenience

Question 6

List disadvantages of mucoadhesion

Answer 6

• Small area of absorption (nasal, oral)
  ~100cm^2 not suitable for low potency drugs
• Limited by taste (oral)
• Delivery limited by molecular weight of a drug (small preferred)
• Local tissue irritation, sensitivity to pathologic conditions

Question 7

List the functions of mucus

Answer 7

• Mucus coats nearly all entry points to the human body that are not covered by skin
• Protects underlying epithelial tissues (e.g stomach)
• Keeps the mucosal membrane moist → lubrication

Question 8

Define “mucus”

Answer 8

• Gel like layer covering the mucous layer/protective layer
• Secreted by goblet cells or specialized glands (e.g salivary glands in the oral cavity)
• Diffusion barrier for drugs

Question 9

Name the components of mucus

Answer 9

• Mostly water
• Mucin (20% proteins/80% carbohydrates)
  (glycoprotein → protein that is surrounded with sugar)
• Lipids
• Inorganic salts

Question 10

Describe carbohydrates in mucin

Answer 10

• Extra large molecules either membrane bound or secreted
• Highly glycosylated/sugar decorated
• Provides a gel-like structure of the mucus
• Carries a negative charge attributed to high content of sialic acid (sugar) (the negative charge comes from deprotonated carboxyl group)
• Brings in a lot of hydroxyl groups

Question 11

List the types of mucoadhesive polymers

Answer 11

• Anionic: mostly carboxyl groups
• Cationic / Electrostatic: contains amine groups
• Non-ionic: mostly hydrocarbons

Question 12

What kind of force will be involved in mucoadhesion based on a structure that contains amine groups?

Answer 12

cationic / electrostatic force

Question 13

List the different types of oral mucosa

Answer 13

• Buccal mucosa: on the cheeks (lip and cheek lining)
• Sublingual mucosa: ventral side of the tongue and the floor of the mouth
• Gingival (gums)

Question 14

Describe drug delivery via buccal mucosa

Answer 14

• Relatively less permeable than sublingual
• Slower absorption and onset of action than sublingual
• Less influenced by saliva
• Suitable for sustained delivery applications

Question 15

Describe drug delivery via sublingual mucosa

Answer 15

• Relatively permeable
• Rapid onset
• Suitable for frequent dosing and short-term delivery (emergencies)

Question 16

Describe transcellular (intracellular) drug absorption

Answer 16

the drug goes in between the two cells avoiding the first-pass effect

Question 17

Describe paracellular (intercellular) drug absorption

Answer 17

the drug goes through one cell avoiding the first-pass effect

Question 18

Name the main barrier to drug absorption via trans- & para-cellular routes

Answer 18

the epithelium

Question 19

Describe the characteristics of drugs delivered via oral mucosa

Answer 19

• Predominantly lipophilic
• Mostly small molecular weight drugs

Maybe hydrophilic macromolecular weight drugs such as peptides, oligonucleotides, polysaccharides:
- Likely require absorption enhancers (e.g. fatty acids, bile salts, surfactants)
- May not be stable due to salivary enzymes

Question 20

Describe the components of buccal tablets

Answer 20

• Bioadhesive polymer layer (second layer allows for drug delivery for absorption)
• There is a matrix that contains the A.I + excipients

Question 21

Explain the proper way to use Oravig (buccal drug delivery system)

Answer 21

• Place the drug with your finger on the outside of your upper lip for 30 seconds
• Holding the drug for 30 seconds will ensure the drug will attach your gum

Question 22

Explain how to properly use Fentora (buccal drug delivery system)

Answer 22

• Starting treatment: place the drug between the upper cheek and gum
• Maintenance treatment: place the drug under tongue and let dissolve
• Counseling tips: Do not crush, spit, or chew

Question 23

Describe the proper way to use Actiq

Answer 23

Place the end of the unit in your mouth and just suck on it

Question 24

List advantages of nasal drug delivery

Answer 24

• Avoidances of hepatic first-pass elimination and destruction in the GI tract
• Rapid absorption of drug molecules across the nasal membrane
• Relatively easy and convenient (non-invasive)

Question 25

List disadvantages of nasal drug delivery

Answer 25

- Possible tissue irritation - Rapid removal of the drug from the site of the absorption (mucociliary clearance) - the drug may not stay in the site of absorption for a long enough time - Pathologic conditions such as cold or allergies that may alter significantly the nasal bioavailability - Limited area of drug absorption (not ideal for drugs with **low** potency)

Question 26

Name the regions of the nasal cavity that are used as drug delivery routes

Answer 26

- olfactory region - respiratory region

Question 27

Describe the olfactory region of the nasal cavity

Answer 27

- connected to sense of smell, allowing you to deliver drugs to nose (via lipophilic molecules) - small surface (1-5 cm2) - provides a direct connection between the central nervous system and the atmosphere (delivers drugs directly to brain)

Question 28

Describe the respiratory region of the nasal cavity

Answer 28

- main site for systemic drug delivery (well vascularized) - relatively large surface area (~150 cm2) - epithelium covered with mucus

Question 29

Explain the role of mucosal epithelium in the respiratory region of the nasal cavity

Answer 29

- humidification and warming of inhaled air - physical and enzymatic protection against foreign compounds (includes drugs) → making this a barrier - mucus sticks to inhaled particles or pathogens and lets them be removed by mucociliary clearance

Question 30

List drugs that are delivered systemically via the nasal cavity

Answer 30

- Analgesics (morphine) - Cardiovascular drugs (propranolol, carvedilol) - Hormones (levonorgestrel, progesterone, insulin) - Anti-inflammatory agents (indomethacin, ketorolac) - Anti-viral (acyclovir)

Question 31

List drugs that are delivered locally via the nasal cavity

Answer 31

- Antihistamines, corticosteroids (rhinosinusitis) - Nasal decongestants (cold symptoms) **for tx of topical nasal disorders**

Question 32

List the requirements for ocular drug delivery

Answer 32

- needs to be clear - good corneal penetration - prolonged contact time with the corneal epithelium - simple to use - non-irritating, comfortable

Question 33

List common challenges for ocular drug delivery

Answer 33

- loss due to dilution in the tear film, fluid spillage, drainage - short residence time - not much flexibility in formulation adjustments

Question 34

Give an example of drug loss during ocular drug delivery

Answer 34

eye drop = 20-50 uL, BUT precorneal space accommodates only ~7ul

Question 35

Explain why drug residence time is short when delivered ocularlly

Answer 35

rapid turnover of tears and aqueous humor

Question 36

What is one strategy for reducing the drainage of eyedrops?

Answer 36

reduce drainage by the use of viscosity-enhancers

Question 37

List viscosity-enhancers used to reduce the drainage of eyedrops

Answer 37

- polyvinyl alcohol, methyl cellulose - timoptix-XE gel (GELRITE gellan gum) - DuraSite (polyacrylic acid formulations)

Question 38

List the features of a port delivery system

Answer 38

- permanent, refillable implant (in the eye) - surgically inserted through a small incision in the sclera and pars plana - four components

Question 39

List the four components of a port delivery system

Answer 39

- extrascleral flange - self-sealing septum - body (drug reservoir) - porous meal release control element