Mucosal Flashcards
Mucosal Drug Delivery
- more permeable than the skin
- accessible body cavities covered with mucosa
oral mucosa (buccal, sublingual, gingival)
nasal
vaginal
intrauterine
rectal
ocular
pulmonary
Advantages of Mucosal Drug Delivery
systemic or local
avoid the 1st pass effect
non-invasive
relatively easy and convenient
Disadvantages of Mucosal Drug Delivery
small area of absorption
taste
delivery limited by MW of drug
local tissue irritation or sensitivity
Mucus
- 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
Components of Mucus
mostly water
mucin (glycoprotein)
lipids
inorganic salts
Mucin
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
Mucin Structure
Sialic Acid (-)
- carboxylic group
- hydroxyl groups
Galactose
N-acetylglucosamine
Core Sugar
Protein
- contains cysteine that can form disulfide bonds
Mucoadhesion
- state in which a polymer and mucus are held together for extended periods of time by interfacial forces
- prolongs residence time of dosage form
Purpose of Mucoadhesion
- controlled release systems
- enhancement of poorly absorbed drug molecules
- immobilization of dosage form at site of action
Features of Mucoadhesion
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
Oral Mucosal
- systemic or local
- 2 types: sublingual (thinner and more permeable) and buccal (thicker and relatively less permeable)
Advantages of Oral Mucosal
avoid first pass effect
rapid absorption and onset
easy to remove if therapy needs d/c
Disadvantages of Oral Mucosal
small surface area –> not suitable for low potency drugs
limited by taste
Sublingual
- relatively permeable
- rapid onset
- suitable for frequent dosing and short-term delivery –> emergency
Ex. nitroglycerin
Buccal
- relatively less permeable than sublingual
- slower absorption and onset than sublingual
- less influenced by saliva
- suitable for sustained delivery –> longer periods of time
Drug Absorption
Mechanisms
- Transcellular (intracellular)
- Paracellular (intercellular)
Absorbed into reticulated and jugular veins and drained into systemic circulation (avoids 1st pass effect)
Characteristics of Drugs for Oral Mucosa
- lipophilic
- small MW drugs
- potentially hydrophilic small drugs like peptides if enhancer is used
Example of Buccal Tablet
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
Actiq
- 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
Buccal Patch
- 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
Advantage of Nasal
avoids 1st pass elimination and destruction of GI tract
rapid absorption of drug across nasal membrane (relatevely permeable)
easy and convenient
Disadvantage of Nasal
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)
Nasal Examples
Zicam
- zinc ion for cold
Miacalcin Nasal Spray
- calcitonin for post menopausal osteoporosis
- long term delivery
Nasal Cavity Anatomy
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
Nasal Vaccines
- 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
Advantage of Vaginal Mucosa
rich bloody supply
high permeability to certain drugs
avoidance of 1st pass effect
Disadvantage of Vaginal Mucosa
hormone dependent changes (pH)
Types of Vaginal Delivery Systems
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
Intrauterine Device
- small plastic device placed into uterus for sustained drug release
- releases progesterone, levonorgestrel
- zero order release for 5 years
Rectal Mucosa
- Local: inflammatory bowel disease
- Systemic: when oral administrations is not feasible
- very good bioavailability
PEDIATRICS AND GERIATRICS AND SUBCONSCIOUS
Suppositories
- drug+wax where they melt, soften, or dissolve and exert local or systemic drug delivery
- long lasting but less concentration (not very high)
Rectal enemas
- liquid introduced into rectum and colon
- good absorption and bioavailability
Ocular
LOCAL: cant deliver systemically very well because of retina blood barrier
Requirements for Ocular Delivery
need to be clear
good corneal penetration
prolonged contact time with epithelium
simplicity of use
non irritating
Challenges in Ocular Delivery
- 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
Ocular Dosage Forms
- 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
Intraocular Implant
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
Encapsulated Cell Technology
- 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
Port Delivery System
- 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
