bioadhasives Flashcards
What is bioadhesion?
the attachment or association of a drug carrier system to a biological surface for extended periods of time
What is a drug carrier system?
any pharmaceutical dosage form containing a bioadhesive polymer or ligand
2 types of biological surfaces and their type of adhesion
- mucus layer lining the biological membrane - mucoadhesion
2. epithelial cells beneath the mucus - cytoadhesion
mucous membrane
epithelial cell layer covered by mucous layer
single cell layer or stratified multilayer
mucus
secreted by goblet cells or specialised glands
viscoelastic gel matrix or mucin glycoproteins
mucus thickness varies
- 50-450 microm in stomach
- <1 microm in mouth
mucous turnover
around 4-5hrs
affects resistance time of mucoadhesive formulation
nature of mucoadhesive bonds
- non-specific interactions between mucous and mucoadhesive polymer
- physical or mechanical interactions
- chemical bonds
- > ionic (mucous is -ve charged), H bonds, van der waals interactions
types of mucoadhesive polymers
- hydrogels
2. hydrophobic polymers
What are hydrogels?
hydrophilic polymer with swelling capacity
examples of hydrogels
carbopols
chitosan (+ve charge, can ionic bond)
sodium alginate
cellulose derivatives
type of delivery for hydrogels
buccal
nasal
most popular mucoadhesive polymer
hydrogels
What are hydrophobic polymers?
non-swellable
- only van der waals interactions
example of hydrophobic polymer
polylactic acid (PLA)
type of delivery for hydrophobic polymers
oral delivery
properties of mucoadhesive hydrogels
hydrophilic functional group
high Mr
cross linked network
hydrophilic functional group of hydrogels
form H bonds or ionic bonds with the mucus layer
water uptake results in polymer swelling and chain disentanglement
3 types of hydrophilic functional groups of hydrogels
- anionic polymers - H bonding interaction with mucin, eg carbomer
- cationic polymers - ionic and H bonding interaction with mucin, eg chitosan
- non-ionic - H bonding interaction with mucin
high Mr of hydrogels
- polymer chain length -> entanglement with mucin chains
- optimin Mw = 10,000-4.000.000 Da
- too high Mr - slow hydration and inadequate bond formation
- too low Mr - excessive hydration, gel formation and complete dissolution in ucus, loss of adhesive ability
cross linked networks
degree of cross linking affects swelling capacity and chain mobility
high degre of cross linking may prevent over hydration but may restrict chain mobility
-> need partial cross linking, retains liquid behaviour so it can continue to interact
drug release process from mucoadhesive hydrogels
- hydration of polymer and swelling of network
- chain relaxation and difusion of dissolved drug
What is cytoadhesion?
adhesion to cells
cell specific bioadhesion
- a recognition ligand is attached to the drug carrier
- useful for oral delivery
cell specific ligands
- lectins
- bacterial adhesins
What are lectins?
proteins or glycoproteins that specifically recognise and bind reversibly to specific carbohydrate residues in the intestinal epithelium
lectins characcteristics
plant origin
- tomato lectin, asparagus pea lectin (can interact with foods)
highly specific binding
mucus may inactivate them
bioinvasion
- after binding, undergo cellular uptake
- facilitate intracellular transport of drug
benefits of bioadhesion drug delivery
enhanced bioavailability
- prolonged residence time
- dec dosing frequency
- inc in conc gradient
target drug delivery to site of action or site of absorption
- localisation of the delivery system at a given target site
mucoadhesive in vitro testing
force of attachment - measurement of adhesive strength between polymer and substrate
rheological measurement
location of mucosal membranes in body
GIT (oral, oesophageal tisue, stomach, small/large intestine) nasal cavity respiratory tract ophthalmic (ocular) cavity rectal cavoty vaginal cavity
advantages of buccoadhesive drug delivery
- drugs with GI s/e and/or oral metabolism (bypasses GIT)
- high blood supply
- robust epithelium (no permanent damage)
- accessibility
- resistant to removal by saliva flow and mechanical stress
disadvantages of buccoadhesive drug delivery
- low permeability
- > skin keratinised areas: gum, palates (barriers to absorption)
- > non keratinised areas: sublingual, cheeks (good)
- over hydration of polymer by saliva
- mucus and epithelial cell turnover (5-6 days - long)
- accidental swallowing
dosage forms for buccoadhesive systems
powder tablet patches gels pastes
-> non-irritant, small, flexible
buccoadhesive systems for local effects
Orahesive powder
Orabase paste
-> for mouth ulcers
buccoadhesive systems for systemic effects
Buccastem
Suscard
mucoadhesive hydrogels for buccoadhesive systems
Carbopol
polycarbophil
penetration enhancer if required
advantages of nasal bioadhesive drug delivery
- drug with GI s/e and/or high 1st pass metabolism
- accessibility
- patient compliance
advantages of nasal bioadhesive drug delivery
- drug with GI s/e and/or high 1st pass metabolism
- accessibility
- patient compliance
disadvantages of nasal bioadhesive drug delivery
- low permeability
- mucociliary clearance
- turn over time for mucus is 10-15mins
- epithelial damage by penetration enhancers
-> not the best form
dosage forms of nasal bioadhesive systems
viscous solutions
gels
powders
polymeric microparticles
local effects of nasal bioadhesive systems
budesonide for allergy
systemic uses of nasal bioadhesive systems
ketotolac for pain
antibiotics
vaccines (nasalflu vaccine)
peptides
mucoadhesive hydrogels for nasal bioadhesive systems
Carbopol
chitosan
xanthan gum
HPMC derivatives
types of dosage forms for oral bioadhesive delivery systems
mucoadhesive or cytoadhesive dosage forms
- tablets, multiparticulate suspensions
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properties of mucoadhesive dosage forms for ORAL bioadhesive systems
hydrophobic polymer (non-swellable) eg poly lactic acis
-> hydrogels are NOT appropriate (dissolves easily in GIT, will lose adhesive effect, want to avoid this)
limitations of oral bioadhesive dosage forms
dosage form elimination
lack of specificity
advantage of cytoadhesive dosage forms for ORAL bioadhesive delivery systems
targeting of specific sites in GIT
- area of max absorption (eg small intestine)
- area where a local effect may be required
2 therapies used in OESOPHAGEAL bioadhesive delivery systems
- anti-relfux therapy
- sodium alginate mucoadhesive gel
- protective layer adhered to oesophageal tissue
- Gaviscon infant - anti cancer therapy
- localisation of Tx
advantages of VAGINAL mucoadhesive systems
- avoidance of 1st pass metabolism
- large SA
- rich blood supply
- mucoadhesive formulations increase retention
disadvantages of VAGINAL mucoadhesive systems
- clearance by vaginal fluids (poor retention)
- variable thickness of vaginal epithelium (rate and extent of absorption
- potential mucosal irritation and damage to epithelium
dosage forms of vaginal mucoadhesive systems
gels
pessaries
creams
films
LOCAL effects for VAGINAL mucoadhesive systems
microbiocides for HIV prophylaxis
labour inducers (Prostin E2)
contraceptive (BufferGel)
antimicrobial (Canesten)
SYSTEMIC effects of VAGINAL mucoadhesive systems
treatment of STD
vaccine delivery
Tx of cervical neoplasias
advantages of RECTAL mucoadhesive systems
- avoidance of 1st pass metabolism (drug absorbed by interior rectal veins)
- large SA (300cm sq)
- rich blood supply
- mucoadhesion formulations inc retention
disadvantage of RECTAL mucoadhesive systems
potential mucosal irritation and damage to epithelium
dosage forms of RECTAL mucoadhesive systems
suppositories gels creams films thermoreversible mucoadhesive suppositories
LOCAL effects of RECTAL mucoadhesive systems
constipation
haemorrhoids
ulcerative colitis
SYSTEMIC effects of RECTAL mucoadhesive systems
anticonvulsant therapy
