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PHRM 829 Exam 3 > Mucosal > Flashcards

Mucosal Flashcards

1
Q

Mucosal Drug Delivery

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

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

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2
Q

Advantages of Mucosal Drug Delivery

A

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

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3
Q

Disadvantages of Mucosal Drug Delivery

A

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

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4
Q

Mucus

A
  • 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

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5
Q

Components of Mucus

A

mostly water
mucin (glycoprotein)
lipids
inorganic salts

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6
Q

Mucin

A

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

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7
Q

Mucin Structure

A

Sialic Acid (-)
- carboxylic group
- hydroxyl groups

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

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8
Q

Mucoadhesion

A
  • state in which a polymer and mucus are held together for extended periods of time by interfacial forces
  • prolongs residence time of dosage form
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9
Q

Purpose of Mucoadhesion

A
  • controlled release systems
  • enhancement of poorly absorbed drug molecules
  • immobilization of dosage form at site of action
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10
Q

Features of Mucoadhesion

A

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

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11
Q

Oral Mucosal

A
  • systemic or local
  • 2 types: sublingual (thinner and more permeable) and buccal (thicker and relatively less permeable)
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12
Q

Advantages of Oral Mucosal

A

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

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13
Q

Disadvantages of Oral Mucosal

A

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

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14
Q

Sublingual

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

Ex. nitroglycerin

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15
Q

Buccal

A
  • relatively less permeable than sublingual
  • slower absorption and onset than sublingual
  • less influenced by saliva
  • suitable for sustained delivery –> longer periods of time
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16
Q

Drug Absorption

A

Mechanisms
- Transcellular (intracellular)
- Paracellular (intercellular)

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

17
Q

Characteristics of Drugs for Oral Mucosa

A
  • lipophilic
  • small MW drugs
  • potentially hydrophilic small drugs like peptides if enhancer is used
18
Q

Example of Buccal Tablet

A

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

19
Q

Actiq

A
  • 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
20
Q

Buccal Patch

A
  • 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

21
Q

Advantage of Nasal

A

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

22
Q

Disadvantage of Nasal

A

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)

23
Q

Nasal Examples

A

Zicam
- zinc ion for cold

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

24
Q

Nasal Cavity Anatomy

A

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

25
Q

Nasal Vaccines

A
  • 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
26
Q

Advantage of Vaginal Mucosa

A

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

27
Q

Disadvantage of Vaginal Mucosa

A

hormone dependent changes (pH)

28
Q

Types of Vaginal Delivery Systems

A

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

29
Q

Intrauterine Device

A
  • small plastic device placed into uterus for sustained drug release
  • releases progesterone, levonorgestrel
  • zero order release for 5 years
30
Q

Rectal Mucosa

A
  • Local: inflammatory bowel disease
  • Systemic: when oral administrations is not feasible
  • very good bioavailability

PEDIATRICS AND GERIATRICS AND SUBCONSCIOUS

31
Q

Suppositories

A
  • drug+wax where they melt, soften, or dissolve and exert local or systemic drug delivery
  • long lasting but less concentration (not very high)
32
Q

Rectal enemas

A
  • liquid introduced into rectum and colon
  • good absorption and bioavailability
33
Q

Ocular

A

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

34
Q

Requirements for Ocular Delivery

A

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

35
Q

Challenges in Ocular Delivery

A
  • 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
36
Q

Ocular Dosage Forms

A
  • 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
37
Q

Intraocular Implant

A

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

38
Q

Encapsulated Cell Technology

A
  • 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
39
Q

Port Delivery System

A
  • 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

PHRM 829 Exam 3 (4 decks)

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