22: Mucosal Flashcards
mucosal drug delivery
-via accessible body cavities covered with mucosa
-oral, nasal etc
-systemic or local
-mucoadhesion
Advantages of mucosal drug delivery
-avoid first pass
-non-invasive
-ease/convenience
disadvantages of mucosal delivery
-small area of absorption
-taste
-limited by weight of drug
-local tissue irritation, sensitivity to pathologic conditions
Mucus
-secreted by goblet cells or salivary glands
-mostly water, mucins, lipids, salts
-diffusion barrier for drugs
-target for mucoadhesionm
mucus functions
-coats all entry points to human body not covered by skin
-protects underlying epithelial tissues
-keeps mucosal membrane moist = lubrication
Mucin
-highly glycosolated proteins
-large molecules either membrane bound or secreted
-provides gel-like structure of mucus
-carries negative charge attributed to high content of sugar
Mucin structure
-cystein rich subdomains
-disulfide bonds
-protein and sugars
Mucoadhesion
-state in which polymers and mucus are held together by interfacial forces
-prolongs residence time
Mucoadhesion purposes
-controlled release
-enhance poorly absorbed drugs
-immobilization of the dosage form at desired state of action
Mechs of mucoadhesion
-electrostatic interaction
-hydrogen bonding
-covalent bonding
-physical interpenetration
Electrostatic interaction
-positive charged polymer + negative charged sialic acid in mucin
Hydrogen bonding
-COOH
-OH
-NH2
Covalent bonding
-disulfide bond between thiolated polymer and cysteine-rich portion of mucin
Structures?
slides 13-15
Oral mucosal
-systemic or local
-sublingual and buccal mucosa
oral mucosal advantages
-avoid first-pass effect
-rapid absorption and onset of drug effect
-easy to remove if therapy needs to be discontinued
oral mucosal disadvantages
-small surface area not good for low potency drugs
-limited by taste
slide17
slide17
Sublingual oral mucosal
-relatively permeable
-rapid onset
-more saliva = more mucus
-suitable for freq dosing and short-term delivery
Buccal oral mucosal
-less permeable than sublingual
-slower absorption and onset
-less influenced by saliva
-suitable for sustained delivery applications
-buccal tablets, patches, semisolids
Drug absorption via oral mucosal
-epithelium is a barrier
-transcellular
-paracellular by lipids
-absorbed into reticulated and jugular veins = drained into systemic circulation = avoid first pass
Drugs delivered via oral mucosa
-mostly lipophillic
-mostly small molecular weight drugs
-MAYBE hydrophillic macromolecular weight drugs such as peptides, oligonucleotides, polysaccharides but they likely need enhancers bc saliva enzymes
Buccal tablets
-bioadhesive polymer layer
-matrix w active ingredient and excipients
Buccal tablet examples
-Oravig for candidiasis
-Fentora for fentanyl (take buccal first then sublingual if u can handle it)
when taking buccal tablet do NOT
-crush, split, suck, chew, swallow
Actiq
-fentanyl citrate
-lozenge on a stick
-rotate and dissolve against oral tissue
-for transmucosal or GI absorption
Buccal patches
-thinner and more flexible
-less obtrusive, pt like them more
Nasal mucosal advantages
-avoid first pass
-rapid absorption
-easy
nasal mucosal disadvantages
-possible tissue irritation
-rapid clearance from nose
-cold or allergies can mess this up
-limited surface area
Nasal mucosal examples
-Zicam for cold
-Miacalcin for osteoporosis
Nasal cavity regions
-respiratory
-olfactory
nasal respiratory region
-main site for systemic drug delivery
-relatively large surface area
-epithelium w mucus that lubes and warms air and removed foreign particles
nasal olfactory region
-small surface area
-provides direct connection between CNS and atmosphere
-small glands that produce solvent for odorous substances
Nasal systemic mucosal delivery
-via respiratory region
-fast and extended drug absorption
-analgesics, CVD, hormones, anti-inflammatory and anti-viral
Local nasal mucosal drug delivery
-treat topical nasal disorders
-antihistamines and corticosteroids for rhinosinusitits
-decongestants for colds
Nasal vaccines
-lymph tissue under nasal epithelium rich w dendritic cells, t cells, b cells bc it first site of contact w antigens
-vax against respiratory infections
potential route for nasal drug delivery to CNS
-via olfactory region
Vaginal mucosal drug delivery
-permeation across epithelial membrane
-gel, creams, films, rings
vaginal delivery advantages
-rich blood supply
-high permeability
-avoidance of hepatic first pass
disadvantages of vaginal admin
-hormone-dependent changes
-pH
vaginal gels and creams
-leaky, messy, need applicator
-estrogen, spermicide
Intrauterine drug delivery
-IUD in uterine cavity
-progesterone and levonorgestrel
-local effects in uterine cavity
-5 years
rectal drug delivery
-drugs normally admin by oral can be put here too ! :)
-local: IBD
-systemic: when u cant do oral
-less popular now
-kids and olds
Rectal dosage forms
-suppositories (solid that melts/dissolves)
-rectal emenas (liquids)
Ocular drug delivery
-local is greatly needed bc blood-retina barrier
Requirements for ocular drug delivery
-need to be clear
-good corneal penetration
-prolonged contact time w corneal epithelium
-simplicity of use
-comfy
Challenges in ocular delivery
-loss due to dilution in tears, spillage, drainage
-short residence time
-not much flexibility in terms of pH, osmolarity, solubility
Ocular dosage forms
-eye drops
-ointments
-ocusert
-contacts
-implants
How to improve eye drops
-viscosity enhancers to reduce drainage
Port delivery system
-permanent refillable implant
-insicion in eye
-flange, sealing septum, body, porous release control element
