exam 3 lecture 9 mucosal Flashcards
mucosal drug delivery
via accessible body cavities covered with mucosa –> more permeable
oral (buccal, sublingual, gingival)
nasal
vaginal
intrauterine
rectal
ocular
pulmonary
advantages of mucosal drug delivery
avoid first pass
noninvasive
relative ease and convenience
disadvantages mucosal drug delivery
small area of absorption
taste
delivery limited MW of drug
local irriation
mucus
secreted by globlet cells/ salivary glands
functions: coats entry points, protects underlying tissue, keeps membranes moist
thickness varies: <1 um in oral cavity, 450 um in stomach
mucus components
mostly water
mucins (glycoproteins)
lipids
inorganic salts
mucin
glycoproteins: 20% proteins + 80% glycosylated carbs
extra large molecules membrane bound or secreted
gel-like structure of mucus
negative charge due to high sialic acid
mucin structure
sialic acid (-): carboxylic + hydroxyl groups
galactose
n-acetyleglucosamine
core sugars
protein
- contains cysteine rich domains for disulfide bonds
mucoadhesion
hydrogen bonding
state where polymers and mucus are held together by interfacial bonds
prolongs residence time of dosage form on the mucosal surface
puprposes of mucoadhesion
controlled released system
enhancement of poorly absorbed drug molecules
immobilization of dosage form at site of action
mechanisms of mucoadhesion
electrostatic interaction: positive charge of polymer and negative charge of sialic acid
H-bond
covalent bonding: disulfide bonds between thiolated polymer and cysteine-rich portion of mucin
physical interpenetration
oral mucosal
systemic or local
sublingual: more permeable and faster
buccal: less permeable
advantages of oral mucosa
avoid first pass
rapid absorption/onset of drug
easy to remove if therapy needs to be discontinued
disadvantage oral mucosa
small surface area
limited by taste
sublingual
relatively permeable
rapid onset
suitable for frequent dosing
nitroglycerin sublingual tab
buccal
relatively less permeable
slower absorption and onset of action
less influenced by saliva
suitable for sustained delivery
drug absorption oral mucosa
mechanisms:
-transcellular (intracellular)
-paracellular (intercellular)
absorbed into reticulated and jugular veins
drained into systemic circulation (first pass
oral drug characteristics
predominantly lipophillic
mostly small MW drugs
maybe hydrophillic macromolecular weight
buccal tablets
bioadhesive polymer layer (polyacrylic acids, cellulose)
matrix containing API and excipients
ex: oravig (miconazole) + fentora ( cephalon)
applying oravig: flat side on fingertip and push into upper gum
atiq
cephalon
good bioavailability
lozenge on a stick
dosage form is rotating and dissolving against mucosal tissue
self-administer drugs to oral cavity is either transmucosal or GI absorption
buccal patch
thinner and more flexible than buccal tabs
less obtrusive and more acceptable to patients
advantage of nasal
avoids first pass elimination and destruction in GI
rapid absorption of drug molecules
relatively easy and convientn
disadvantage nasal
possible tissue irritation
rapid removal of drug at site absorption
pathological conditions like cold/allergies may alter nasal bioavail
limited area of drug absorption
nasal examples
zicam - zinc for cold symptoms
miacalcin - calcitonin for post-menopausal osteoporosis
nasal cavity
respiratory region: main site for systemic drug delivery
- epithelium covered with mucus for humidification and warming of inhaled air
olfactory region: provides connection from CNS to atmosphere, contains small glands that produce secretions acting as a solvent for odorous
nasal vaccines
nasal mucosa: first site of contact with inhaled antigens (influenza)
lymphoid tissue underneath nasal epithelium
vaccination against respiratory infections
advantage of vaginal mucosa
rich blood supply
high permeability to certain drugs
avoidance of first pass
disadvantage vaginal mucosa
hormone-dependent changes (pH)
vaginal delivery systems
gels + creams: most widely used, drawback is leakage/mess/applicator
films
vaginal rings: pliable drug delivery device inserted into vagina
IUD
small plastic device placed into uterine cavity for sustained UID drug release of contraception
local progestogenic effects in UID cavity
zero order release up to 5 years
rectal mucosa
oral drugs can be admin by lower enteral route through anal portion / rectum
local: IBD
systemic: when oral admin not feasible
suppositories: solid dosage form for rectal insertion
rectal emenas: liquids introduced into rectum and colon via anus
PED and geriatrics
ocular
local: great need for ocular drug delivery
requirements for ocular drug delivery:
-need to be clear
- good corneal penetration
- prolonged contact time with corneal epithelium
- simplicity of use
- non- irritating, comfortable
challenges in ocular delivery
loss due to dilution bc of tear film
short residence time
not much flexibility in formulation adjustments
ocular dosage forms
eye drops - reduce drainage
ointments
ocusert
contact lenses
erodable/ non-erodable implants
intraocular implants
ciliart neurotrophic factor: proteons neural cells including photoreceptors –> slows retinal degradation
blood-retina barrier: restricts drug access from blood to retina tissue
oscular implant: loaded with human retinal pigment epithelium cells with CNTF gene to produce CNTF in situ
encapsulated cell technology
semi-permeable membrane
allows oxygen and nutrients to cross and come in
allows drug to come out
does not allow immune cells to come in
