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bioadhasives Flashcards

1
Q

What is bioadhesion?

A

the attachment or association of a drug carrier system to a biological surface for extended periods of time

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2
Q

What is a drug carrier system?

A

any pharmaceutical dosage form containing a bioadhesive polymer or ligand

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3
Q

2 types of biological surfaces and their type of adhesion

A
  1. mucus layer lining the biological membrane - mucoadhesion

2. epithelial cells beneath the mucus - cytoadhesion

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4
Q

mucous membrane

A

epithelial cell layer covered by mucous layer

single cell layer or stratified multilayer

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4
Q

mucus

A

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
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5
Q

mucous turnover

A

around 4-5hrs

affects resistance time of mucoadhesive formulation

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6
Q

nature of mucoadhesive bonds

A
  • 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
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7
Q

types of mucoadhesive polymers

A
  1. hydrogels

2. hydrophobic polymers

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8
Q

What are hydrogels?

A

hydrophilic polymer with swelling capacity

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9
Q

examples of hydrogels

A

carbopols
chitosan (+ve charge, can ionic bond)
sodium alginate
cellulose derivatives

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10
Q

type of delivery for hydrogels

A

buccal

nasal

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11
Q

most popular mucoadhesive polymer

A

hydrogels

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12
Q

What are hydrophobic polymers?

A

non-swellable

  • only van der waals interactions
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13
Q

example of hydrophobic polymer

A

polylactic acid (PLA)

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14
Q

type of delivery for hydrophobic polymers

A

oral delivery

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15
Q

properties of mucoadhesive hydrogels

A

hydrophilic functional group

high Mr

cross linked network

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16
Q

hydrophilic functional group of hydrogels

A

form H bonds or ionic bonds with the mucus layer

water uptake results in polymer swelling and chain disentanglement

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17
Q

3 types of hydrophilic functional groups of hydrogels

A
  1. anionic polymers - H bonding interaction with mucin, eg carbomer
  2. cationic polymers - ionic and H bonding interaction with mucin, eg chitosan
  3. non-ionic - H bonding interaction with mucin
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18
Q

high Mr of hydrogels

A
  • 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
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19
Q

cross linked networks

A

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

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20
Q

drug release process from mucoadhesive hydrogels

A
  • hydration of polymer and swelling of network

- chain relaxation and difusion of dissolved drug

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21
Q

What is cytoadhesion?

A

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
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22
Q

What are lectins?

A

proteins or glycoproteins that specifically recognise and bind reversibly to specific carbohydrate residues in the intestinal epithelium

23
Q

lectins characcteristics

A

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
24
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
25
mucoadhesive in vitro testing
force of attachment - measurement of adhesive strength between polymer and substrate rheological measurement
26
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 ```
27
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
28
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
29
dosage forms for buccoadhesive systems
``` powder tablet patches gels pastes ``` -> non-irritant, small, flexible
30
buccoadhesive systems for local effects
Orahesive powder Orabase paste -> for mouth ulcers
31
buccoadhesive systems for systemic effects
Buccastem Suscard
32
mucoadhesive hydrogels for buccoadhesive systems
Carbopol polycarbophil penetration enhancer if required
33
advantages of nasal bioadhesive drug delivery
- drug with GI s/e and/or high 1st pass metabolism - accessibility - patient compliance
34
advantages of nasal bioadhesive drug delivery
- drug with GI s/e and/or high 1st pass metabolism - accessibility - patient compliance
35
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
35
dosage forms of nasal bioadhesive systems
viscous solutions gels powders polymeric microparticles
35
local effects of nasal bioadhesive systems
budesonide for allergy
35
systemic uses of nasal bioadhesive systems
ketotolac for pain antibiotics vaccines (nasalflu vaccine) peptides
36
mucoadhesive hydrogels for nasal bioadhesive systems
Carbopol chitosan xanthan gum HPMC derivatives
37
types of dosage forms for oral bioadhesive delivery systems
mucoadhesive or cytoadhesive dosage forms - tablets, multiparticulate suspensions
38
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39
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)
40
limitations of oral bioadhesive dosage forms
dosage form elimination lack of specificity
41
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
42
2 therapies used in OESOPHAGEAL bioadhesive delivery systems
1. anti-relfux therapy - sodium alginate mucoadhesive gel - protective layer adhered to oesophageal tissue - Gaviscon infant 2. anti cancer therapy - localisation of Tx
42
advantages of VAGINAL mucoadhesive systems
- avoidance of 1st pass metabolism - large SA - rich blood supply - mucoadhesive formulations increase retention
43
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
43
dosage forms of vaginal mucoadhesive systems
gels pessaries creams films
43
LOCAL effects for VAGINAL mucoadhesive systems
microbiocides for HIV prophylaxis labour inducers (Prostin E2) contraceptive (BufferGel) antimicrobial (Canesten)
43
SYSTEMIC effects of VAGINAL mucoadhesive systems
treatment of STD vaccine delivery Tx of cervical neoplasias
44
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
45
disadvantage of RECTAL mucoadhesive systems
potential mucosal irritation and damage to epithelium
46
dosage forms of RECTAL mucoadhesive systems
``` suppositories gels creams films thermoreversible mucoadhesive suppositories ```
47
LOCAL effects of RECTAL mucoadhesive systems
constipation haemorrhoids ulcerative colitis
48
SYSTEMIC effects of RECTAL mucoadhesive systems
anticonvulsant therapy

PHA333 (27 decks)

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