bio adhesive systems Flashcards
define bioadhesion
The attachment or association of a drug carrier system to a
biological surface, for extended periods of time
define a drug carrier system
any pharmaceutical dosage form
containing a bioadhesive polymer or ligand
what is a bioogical surface?
– Mucus layer lining the biological membrane - mucoadhesion
– Epithelial cells beneath the mucus - cytoadhesion
how is the mucous membrane made uo?
- Epithelial cell layer covered by mucous layer
* Single cell layer or stratified multilayer
what is mucus?
- Secreted by goblet cells or specialised glands
- Viscoelastic gel matrix of mucin glycoproteins
- Mucus thickness varies: 50-450 μm in stomach; < 1 μm in mouth
how long does it take for mucus turnover?
- Variable ~ 4-5 hours
* Affects residence time of mucoadhesive formulation
what is the nature of a mucoadhesive bond?
• Non-specific interactions between mucus and
mucoadhesive polymer
• Physical or mechanical interactions
• Chemical bonds
what are the type of chemical bonds in a mucoadhesive bond?
- Ionic bonds (mucus is -ve charged)
- H-bonds
- Van der Waal’s interactions
what are the different types of mucoadhesive polymers?
hydrogela
hydophobic polymers
how is a hydrogel made up? how is it delivered?
Hydrophilic polymers with swelling capacity
• e.g. Carbopols, chitosan (+ve charged), sodium alginate, cellulose derivatives
• Buccal / nasal delivery
• Most popular mucoadhesive polymers
how is a hydrophobic polymer made up? what route of delivery is it given by?
- Non-swellable
- e.g. polylactic acid (PLA)
- Oral delivery
how do hydrophilic functional groups bond?
- Form H-bonds or ionic bonds with the mucus layer
* Water uptake results to polymer swelling and chain disentanglement
what are the different types of hydrophilic functional groups and how do they bond?
- Anionic polymers
- H-bonding interaction with mucin
- E.g. Carbomer
- Cationic polymers
- Ionic and H-bonding interaction with mucin
- E.g. Chitosan
- Non ionic
- H-bonding interaction with mucin
what are the properties of mucoadhesive hydrogels?
hydrophilic functional groups
high MW
cross-linked networks
what is the optomum MW dor mucoadhesive hydrogels?
10,000 –4,000,000 Da
what happens if the MW is too high?
slow hydration (swelling) and inadequate bond formation with mucus
what happens if the MW is too low?
excessive hydration, gel formation and complete
dissolution in mucus, loss of adhesive ability
what does the degree of cross linking affect?
swelling capacity and chain mobility
what may a high degree of cross linking cause?
may prevent over-hydration but may restrict chain mobility
what happens in the drug release process from mucoadhesive hydrogels?
- Hydration of polymer and swelling of network
* Chain relaxation and diffusion of dissolved drug
what occurs in cytoadhesion?
• Cell-specific bioadhesion – A recognition ligand is conjugated to the drug carrier system – 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
what are the properties of lectins?
- Plant origin e.g. tomato lectin, asparagus pea lectin
- Highly specific binding
- Mucus may inactivate them
- Bioinvasion
what occurs in bioinvasion in lectins?
- After binding, they undergo cellular uptake
* Facilitate intracellular transport of drug
what are the benefits of bioadhesion to drug delivery?
• Enhanced bioavailability
• Prolonged residence time
• Decreased dosing frequency
• Increase in concentration gradient
• Target drug delivery to site of action or site of
absorption
• Localisation of the delivery system at a given target site
how do you test mucoadhesive in vitro?
Force of attachment
– Measurement of adhesive strength between polymer and
substrate
• Rheological measurement
what are the different locations of mucosal membranes?
• GI tract Oral cavity (buccoadhesion) Oesophageal tissue Stomach Small / large intestine • Nasal cavity • Respiratory tract • Ophthalmic (ocular) cavity • Rectal cavity • Vaginal cavity
what are the advanatages of buccodhesive drug delivery?
• Drugs with GI side effects or/and high metabolism • High blood supply • Robust epithelium No permanent damage • Accessibility • Resistant to removal by saliva flow and mechanical stress
what are the disadvantages of buccoadhesive drug delivery?
• Low permeability Skin < buccal cavity < small intestine Keratinised areas: gums, palates Non-keratinised areas: sublingual, cheeks • Over-hydration of polymer by saliva • Mucus and epithelial cell turnover 5-6 days • Accidental swallowing
what are the dosage forms availible to buccoadhesive systems? how are they beneficial?
Powder, tablets, patches, gels, pastes
Non-irritant, small, flexible
what are the local or systemic effects produced by buccoadhesive systems?
Orahesive® powder, Orabase® paste
Buccastem®, Suscard
what are some examples of mucoadhesive hydrogels for buccadhesive systems?
Carbopol, polycarbophil, penetration enhancer if required
what are the advantages of nasal bioadhesive drug delivery?
• Drug with GI side effects or/and
with high 1st pass metabolism
• Accessibility
• Patient compliance
what are the disadvantages of nasal bioadhesive drug delivery systems?
• Low permeability • Mucociliary clearance • Turn-over time for mucus is 10-15 minutes. • Epithelial damage by penetration enhancers
what are the dosage forms availible in nasal bioadhesive systems?
Viscous solutions, gels, powders, polymeric microparticles
what are the local or systemic effects in the nasal bioadhesive systems?
Budesonide (nasal allergy)
E.g. ketorolac (pain), antibiotics, vaccines, peptides
what are some examples of mucoadhesive hydrogels for nasal bioadhesive systems?
Carbopol, chitosan, xanthan gum, HPMC derivatives
what are the forms availible for roal bioadhesive delivery systems?
– Tablets, multiparticulate suspensions
what are the availible muoadhesive dosage forms for oral bioadhesive delivery systems?
– Hydrophobic polymer (non-swellable) e.g. poly lactic acid
– Hydrogels are not appropriate
what are limitations of oral mucoadhesive dosage forms?
– Dosage form elimination
– Lack of specificity
what use are cytoadhesive dosage forms?
– Targeting of specific sites in the GI tract
• Area of maximum absorption
• Area where a local effect may be required
what is oesophageal delivery systems used for?
anti reflux therapy
anticancer therapy
what are the advantages of vaginal mucoadhesive systems?
• Avoidance of 1st pass metabolism • Large surface area • Rich blood supply • Mucoadhesive formulations increase retention
what are the disadvantages of vaginal delivery systems?
Clearance by vaginal fluids Poor retention • Variable thickness of vaginal epithelium Rate and extent of absorption • Potential mucosal irritation and damage to epithelium
what are the systemic or local effects for the vaginal mucoadhesive systemms?
Local: microbiocides for HIV prophylaxis, labour inducers
(e.g. Prostin E2®), contraceptive (e.g. BufferGel®),
antimicrobial (e.g. Canesten)
Systemic: treatment of STD, vaccine delivery, treatment
of cervical neoplasias
what are the advantages of rectal mucoadhesive systems?
Avoidance of 1st pass metabolism When drug is absorbed by inferior rectal veins • Large surface area (300 cm2) • Rich blood supply • Mucoadhesive formulations increase retention
what are the disadvanatges of rectal ?
• Potential mucosal irritation
and damage to epithelium
what are the local or systemic effect?
Local: constipation, haemorrhoids, ulcerative colitis
Systemic: anticonvulsant therapy
