Polymers 5: mucoadhesion Flashcards
Define what mucoadhesion means?
- The interfacial forces that surround the natural or synthetic polymer
- Between the mucus layer that covers the mucosal tissue (wet surfaces on the body)
What are the current routes of administration of mucoadhesives?
- Oral cavity (Buccal, gingival and sublingual)
- Nasal
- Oral
- Ocular
- Vaginal
- Rectal
What are the advantages of mucoadhesive delivery?
- Improved bioavailability - drug has more time penetrate and deposit into tissue, so can use drug once a day instead of twice perhaps
- Increased dosage form residence time
- Reduced administration frequency
- Simplified administration
- Non invasive
- Can target particular section in the body- target CNS through nasal cavities
- Can skip first pass metabolism as it goes right to the blood stream
What is the structure of a mucosal membrane?
- Protein core
- Oligosaccharide side chains
- Terminal Sialic acid
What are mucins?
- Produced by the epithelial cell, they can be bound to the epithelial cell via hydrogen bonding and soluble secreted layer
- Made of polysaccharides
- They are complicated lipoprotein molecules
What are the function of mucosal membranes?
- Lubrication
- Provides physical and chemical protection of epithelial cell against destruction
- Wetting
- Modulation of water content in underlaying tissue
Explain the mechanism of how mucus protects the stomach?
- HCl in the stomach is concentrated enough to digest the stomach itself
- Gastric mucus forms a protective layer over the epithelium to act as a diffusion barrier
What are the characteristics of mucosal surfaces?
- Dynamic surface that is reformed continuously through secretion of mucins
- Short life time
- Efficient semi permeable barrier system to hamper diffusion of many drug molecules and nano medicines
What is the electronic theory?
Electron transfer between the formulation and mucus results formation of electrical double layer at surface
What is the absorption theory?
Attraction between the mucus and the mucoadhesive form is caused by secondary force interactions such as hydrogen bonding and van der waal forces
What is the diffusion theory?
- Interpenetration and entanglement between the mucus proteins and polymer chains of mucoadhesive forms
- Dosage form to mucosal gel
What is the wetting theory?
Correlates the surface tension of the mucus and the mucoadhesive with the ability of the mucoadhesive to swell and spread on the mucus layer
What are the two stages of mucosal adhesion?
- Contact stage will cause swelling and wetting
- Consolidation stage
- Non covalent bond distribution and interpenetration
- Dissolves eventually and releases ingredients slowly
For the performance of mucoadhesiveness, what are the properties that are looked at?
- Mucoadhesive properties (how sticky it is)
2. Biocompatibility
What are the sources of animal tissue used for it’s mucosal membranes and the advantages/disadvantages of them?
- Slaughterhouse
- Advantages:
- No need to breed/kill animals
- Cost efficiency
- No problems with animal activist - Disadvantages:
- Tissues aren’t always fresh
What are the two visual methods for testing a tablet mucoadhesive forms?
- Flow cell method
2. Rotating cylinder method
Describe the flow cell method?
- Place the dosage form on mucosal tissue (example: eye) that’s angled on a ramp
- Use artificial body fluid to try and wash off the dosage form
Explain how the purpose of the rotating cylinder method?
- Used to measure dissolution of dosage form
- Same volume as the stomach
- Mimics the stomach juice and how the tablet dissolves
How do you test for mucosal adhesion of fluorescent nano particles?
- Syringe pump is used containing artificial tear fluid to try wash off the dosage form on an artificial cows eye
- You can then shine it on UV light in order to identify how well the material is washed off from numerous attempts
If it takes longer time for the dosage form to detach from mucosa, what does this mean?
It has better mucoadhesive properties
Describe the experiment on how to work out detachment force (A) and work of adhesion (B) and it’s purpose?
- Attach a tablet to a rod and place it on a biological tissue- work out the force of detaching it from the surface using a graph
- Used to compare which tablet is more adhesive
- The higher the value of detachment force and work of adhesion means better muco-adhesive properties
Describe the in vivo method that’s used for recording mucoadhesive properties?
Animal like a rat’s GI tract is removed and attached onto several fraction collectors, Reservior, Pump and water bath
Give examples of polymers with excellent, good and fair muco-adheisve properties?
- Carboxymethylcellulose (excellent)
- Poly (acrylic acid) (excellent)
- Dextran (good)
- Gelatin (fair)
What are the specific features of mucoadhesive polymers?
- Hydrophillic or water soluble polymers
- Negatively or positively charged (polyelectrolytes)
- If both positively and negatively charged groups are present, muco-adhesion is poor
- Strong hydrogen bonding groups (carboxyl, hydroxyl, amino groups) - strong mucoadhesive properties
What are the factors that influence mucoadhesion?
- Molecular weight of polymers
- Concentration of mucoadhesive
- Chain flexibility and cross linking of polymers
- Presence of non muco-adhesive co-excipients
- pH
- Normally talking about hydrophilic compounds
What are the different types of solid mucoadhesive formations?
- Tablets (above the gum)
- Lozenges
- Inserts (eyes)
- FIlms (sores)
What are the different types of semi solid and liquid formations of mucoadhesive formations?
- Gels and pastes
- Viscous Liquids
- Gel forming liquids
