Mucosal

Question 1

Mucosal Drug Delivery

Answer 1

• more permeable than the skin
• accessible body cavities covered with mucosa

oral mucosa (buccal, sublingual, gingival)
nasal
vaginal
intrauterine
rectal
ocular
pulmonary

Question 2

Advantages of Mucosal Drug Delivery

Answer 2

systemic or local
avoid the 1st pass effect
non-invasive
relatively easy and convenient

Question 3

Disadvantages of Mucosal Drug Delivery

Answer 3

small area of absorption
taste
delivery limited by MW of drug
local tissue irritation or sensitivity

Question 4

Mucus

Answer 4

• secreted by goblet cells or salivary glands

Function:
- mucus coats all entry points to human body not covered by skin
- protects underlying epithelial tissues
- keeps mucosal membranes moist (lubrication)

varies in thickness from < 1 um in oral cavity to 450 um in stomach

Question 5

Components of Mucus

Answer 5

mostly water
mucin (glycoprotein)
lipids
inorganic salts

Question 6

Mucin

Answer 6

Glycoprotein:
- 20% proteins
- 80% highly glycosylated carbohydrates

very large molecules that are either bound to membrane or secreted

provides gel-like structure of the mucus

carries a negative (-) charge attributed to high content of sialic acid

Question 7

Mucin Structure

Answer 7

Sialic Acid (-)
- carboxylic group
- hydroxyl groups

Galactose
N-acetylglucosamine
Core Sugar
Protein
- contains cysteine that can form disulfide bonds

Question 8

Mucoadhesion

Answer 8

• state in which a polymer and mucus are held together for extended periods of time by interfacial forces
• prolongs residence time of dosage form

Question 9

Purpose of Mucoadhesion

Answer 9

• controlled release systems
• enhancement of poorly absorbed drug molecules
• immobilization of dosage form at site of action

Question 10

Features of Mucoadhesion

Answer 10

Sialic Acid (-)
- carboxylic group and hydroxyl group can H bond

Protein
- cysteine amino acid partaking in disulfide bond with a thiolated polymer

Positive Polymer
- sialic acid gives off negative charge allowing for a positive polymer to have electrostatic interactions

Question 11

Oral Mucosal

Answer 11

• systemic or local
• 2 types: sublingual (thinner and more permeable) and buccal (thicker and relatively less permeable)

Question 12

Advantages of Oral Mucosal

Answer 12

avoid first pass effect
rapid absorption and onset
easy to remove if therapy needs d/c

Question 13

Disadvantages of Oral Mucosal

Answer 13

small surface area –> not suitable for low potency drugs
limited by taste

Question 14

Sublingual

Answer 14

• relatively permeable
• rapid onset
• suitable for frequent dosing and short-term delivery –> emergency

Ex. nitroglycerin

Question 15

Buccal

Answer 15

• relatively less permeable than sublingual
• slower absorption and onset than sublingual
• less influenced by saliva
• suitable for sustained delivery –> longer periods of time

Question 16

Drug Absorption

Answer 16

Mechanisms
- Transcellular (intracellular)
- Paracellular (intercellular)

Absorbed into reticulated and jugular veins and drained into systemic circulation (avoids 1st pass effect)

Question 17

Characteristics of Drugs for Oral Mucosa

Answer 17

• lipophilic
• small MW drugs
• potentially hydrophilic small drugs like peptides if enhancer is used

Question 18

Example of Buccal Tablet

Answer 18

Oravig (local)
- Miconazole (antifungal)
- buccal tablet for local treatment of oropharyngeal candidiasis

Fentora (systemic)
- effervescent tablet that rapidly releases fentanyl into buccal pouch –> systemic effect

Question 19

Actiq

Answer 19

• fentanyl citrate as a lozenge on a stick
• administered by rotating and dissolving it against oral mucosal tissue
• can be for either transmucosal or gastrointestinal absorption

Question 20

Buccal Patch

Answer 20

• thinner and more flexible than buccal tablets
• less obtrusive and more acceptable to patients
• contains water impermeable back layer, API layer, mucoadhesive layer

Ex. Dentipatch (lidocaine) and BEMA

Question 21

Advantage of Nasal

Answer 21

avoids 1st pass elimination and destruction of GI tract
rapid absorption of drug across nasal membrane (relatevely permeable)
easy and convenient

Question 22

Disadvantage of Nasal

Answer 22

tissue irritation
rapid removal of drug from site of absorption (mucociliary clearance)
cold or allergies can alter nasal bioavailability
limited area of drug absorption
risk of affecting olfactory system (smell)

Question 23

Nasal Examples

Answer 23

Zicam
- zinc ion for cold

Miacalcin Nasal Spray
- calcitonin for post menopausal osteoporosis
- long term delivery

Question 24

Nasal Cavity Anatomy

Answer 24

Respiratory Region
- main site for systemic drug delivery
- large surface area (150 cm2)
- Function:
**humidification and warming of inhaled air
**physical and enzymatic protection against foreign compounds

Olfactory Region
- small surface area (1-5 cm2)
- direct connection between CNS and atmosphere
- contains small glands producing secretion acting as solvent for odorous

Question 25

Nasal Vaccines

Answer 25

- Nasal mucosa: 1st site of contact with antigens - lymphoid tissue under epithelium contains dendritic cells, T cells, B cells - vaccines can then be used against respiratory infections

Question 26

Advantage of Vaginal Mucosa

Answer 26

rich bloody supply high permeability to certain drugs avoidance of 1st pass effect

Question 27

Disadvantage of Vaginal Mucosa

Answer 27

hormone dependent changes (pH)

Question 28

Types of Vaginal Delivery Systems

Answer 28

Gels/Creams: - disadvantage: leakage, messy, applicator needed Films Rings: - pliable drug delivery system that can be inserted into vagina where is slowly releases hormones to be absorbed into blood

Question 29

Intrauterine Device

Answer 29

- small plastic device placed into uterus for sustained drug release - releases progesterone, levonorgestrel - zero order release for 5 years

Question 30

Rectal Mucosa

Answer 30

- Local: inflammatory bowel disease - Systemic: when oral administrations is not feasible - very good bioavailability PEDIATRICS AND GERIATRICS AND SUBCONSCIOUS

Question 31

Suppositories

Answer 31

- drug+wax where they melt, soften, or dissolve and exert local or systemic drug delivery - long lasting but less concentration (not very high)

Question 32

Rectal enemas

Answer 32

- liquid introduced into rectum and colon - good absorption and bioavailability

Question 33

Ocular

Answer 33

LOCAL: cant deliver systemically very well because of retina blood barrier

Question 34

Requirements for Ocular Delivery

Answer 34

need to be clear good corneal penetration prolonged contact time with epithelium simplicity of use non irritating

Question 35

Challenges in Ocular Delivery

Answer 35

- loss of drug due to dilution in tear film, fluid spillage, or drainage **very low volume to deal with as corneal only accommodates 7 uL - short residence time **rapid turnover of tears & aqueous humor - not much flexibility in formulation adjustments **must be precise **pH, osmolarity, solubility

Question 36

Ocular Dosage Forms

Answer 36

- eye drops **can contain polyvinvyl alcohol or methylcellulose that thickens and allows it to stay longer --> less drainage **timoptix gel **polyacrylic acid - ointments - ocusert - contact lenses - erodable/non erodable implants - injections

Question 37

Intraocular Implant

Answer 37

CNTF: protects neural cells including photoreceptor cells and retards retinal degeneration Ocular Implant: loaded with human retinal pigment epithelial cells transfected with CNTF gene to produce CNTF

Question 38

Encapsulated Cell Technology

Answer 38

- surrounded by semipermeable membrane - allows O2 and nutrients to feed cells - allows drugs to come out - does not allow immune cells to get in - semi selective on what can get in

Question 39

Port Delivery System

Answer 39

- permanent, refillable implant that is surgically inserted 4 Components: - extrascleral flange (anchor) - self sealing septum - body (drug reservoir) - porous metal release control element refilled every 6 months