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PHRM3021 > Polymers for Drug Delivery > Flashcards

Polymers for Drug Delivery Flashcards

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1
Q

What is polymer?

A

high MW, organic materials made up of long chains of repeating MONOMER units

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2
Q

What are polymers bonded by?

A

Covalent bonds

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3
Q

What do the network junction points do?

A

Provide substance and material cohesion

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4
Q

What are the network junction points in the synthetic polymers?

A

a) physical chain entanglements
b) chemical cross-links
c) crystalline units

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5
Q

What are the network junction points in the natural polymers?
(what are the strong intra/inter chain bonds formed by?)

A

a) H-bonding
b) ion pairing (+ with -)
c) disulphide (S-S)bridges between cysteine groups

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6
Q

What are two molecules with the disulphide bridges?

A

insulin (two bonds link by s-s)

ribonuclease (one chain twisted in a ball by disulphide bridges - very stable!)

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7
Q

What are the polymer properties dependent on?

A

Chemical structure, macromolecular structure, linear/branched structures, cross linking of polymer chains (increased stability)

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8
Q

What are homopolymers?

A

Polymer chains contain one monomer type

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9
Q

What are the examples of homopolymers?

A

polyethylene (PE:CH2CH2), polyethylene glycol (PEG: OCH2CH2)

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10
Q

What do polyethylene glycol (PEG) do?

A

help to dissolve hydrophobic and hydrophilic molecules to be added into tablets

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11
Q

What are two groups of natural polymers?

A
  1. protein-based polymers

2. Polysaccharides

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12
Q

What are examples of protein-based natural polymers?

A

collagen, albumin, gelatin

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13
Q

What are the examples of polysaccharides of natural polymers?

A

agarose, alginate (gel-forming), corrageenan,chitosan

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14
Q

What are the amino acids in proteins linked by?

A

by peptide bonds

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15
Q

What is collagen?

A

fibrous protein, 60% (abundant) of total protein content of mammals

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16
Q

What are the 4 structural levels of collagen?

A

1) protein chain (alpha)
2) collagen molecules (3 x protein chain in helix)
3) Fibrils (packing of collagen molecules)
4) Collagen FIBRES (association of fibrils)

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17
Q

Is collagen temperature sensitive?

A

yes, at >40degrees, they lose the helix structure, forming random coil conformation

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18
Q

What are collagens used in?

A

for artificial skin (injuries, ulcers)

for cosmetic surgery, CR for eye medication, resorbable sutures-녹는실 (discontinued)

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19
Q

Where do we get gelatin from?

A

they are HYDROLYSED COLLAGEN-

by partial hydrolysis (chemical or enzymatic) of animal collagenous tissues, skin, tendons, ligaments, bones

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20
Q

how do we make gelatin?

A

from collagen fibres to water soluble, randomly coiled protein

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21
Q

What is type a gelatin?

A

prepared under ACIDIC condition

isoelectric point pH 7-9

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22
Q

What is type b gelatin?

A

prepared under BASIC condition

isoelecctric point pH 5

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23
Q

What happens to gelatin in terms of temperature?

A

soluble in hot water (60degrees)

becomes gels on cooling

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24
Q

What are gelatin used for?

A

hard/soft capsules
microencapsulation of anticancer drugs
Reversible crosslinking of gelatin required for stability
Reaction of aldehydes with terminal amine groups

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25
What is bad about gelatin?
cytotoxic glutaraldehyde monomers leak from gelatin matrix in vivo
26
What are the biodegradable synthetic polymers?
polyesters (lactic acid+glycolic acid = DL-PLGA), polyanhydrides, polyarrides, phosphorous-based polymers
27
What are the non-debiodegradable syntheic polymers?
cellulose derivatives (carboxymethyl cellulose, hydroxypropyl methyl cellulose), silicones, acrylic polymers (polymethacrylates)
28
Is cellulose soluble in water?
No, virtually insoluble
29
What are methyl cellulose?
synthetic polymer, | methyl ether of cellulose
30
Is methyl cellulose soluble in water?
yes aqueous solubility by partial methylation or carboxymethylation of cellulose
31
What substitutions do the methyl cellulose have?
high density of hydrophobic region and | low density of hydrophyilic region
32
What nature/properties do methyl cellulose have?
AMPHIPHATIC nature and | SURFACTANT properties
33
How is methyl cellulose formed into gel?
by temperature (50degrees), it is reversible on cooling
34
What are different viscosity grades of methyl cellulose used for?
high viscosity: thickening/dispersing agent | low viscosity: emulsifiers for o/w emulsions (as surfactants)
35
What is methyl cellulose used for in the body?
colloidal bulk LAXATIVES - it swells in lower small/large intestine to cause reflex peristalsis) - -> apply pressure to colon --> contraction of colon --> laxative activity
36
What are other cellulose derivatives?
MCC, HPMC, hydroxyethylcellulose
37
What are the properties and uses of MCC?
it is INsoluble in water | it is used for solid dose formation (tablet diluent)
38
What are the properties and uses of HPMC?
it is SOLUBLE in water | it is used for ophthalmic solutions (prolonging DOA of eyedrops)
39
What are the properties of hydroxyethylcellulose?
it is SOLUBLE in water | it does not form gels
40
What are the applications of the cellulose derivatives?
bioadhesive (in mucosa) | water-soluble hydrocolloids for wound dressing (nice and moist)
41
What is the use of MCC in tablet formation?
tablets have challenges in dissolution process when we want to reverse the reduced SA caused by compression (intact tablets) for rapid rate of dissolution We can solve this problem by adding MCC that is insoluble but easily wetted
42
What does cellulose acetate phthalate (CAP) show?
pH depedent dissolution
43
Where is CAP used?
- delay drug release by enteric coating up to beyond stomach, further along GIT, - Reduce SE/irritation to gastric mucosa due to drugs by coating them - Prevent loss of drug activity in low pH in stomach by coating
44
What is the coating technique for CAP?
- polymer dissolution in acetone:Water - tablet coating (eg. fluid bed system) - drying temp at 55-80degrees
45
What is the effect of CAP of aspirin?
Drug release is restricted in simulated gastric fluid (pH 1.2) and pH below 6.2 and released rapidly as it reaches above pH 6.2 (simulated intestinal fluid)
46
What are the properties of different MW of PEG (macrogols) - water soluble synthetic polymer
MW 200-700: liquid, hygroscopic (attract water) | MW >3000: semi-solid, waxy
47
What are the PEG used for?
- mixture of PEG4000 and drugs (sulphathiazole) increase dissolution rate (improved drug wetting) - PEG-drug conjugates prolong the blood circulation times (drug masking reduces destruction by immune system) - PEG hydrogels: PEG (2000-10000) crosslinked using diisocyannate and triol - -> delivers prostaglandin E2 from pessary to help childbirth
48
What is carbopol? (carboxymethylene)
high MW polymer of acrylic acid crosslinked with allyl sucrose
49
What are carbopol's properties in different solutions?
acidic at aqueous solutions due to many carboxyl groups | highly viscous at neutral solutions due to negative charge at pH 7.4 (causes repulsion/uncoiling/gel formation)
50
What does strong binding of carbopol to intestinal mucosal tissue lead to?
- increased residence time at absorption site - increased contact with mucosa (steep drug conc.gradient) - increased bioavailability in specific region
51
What is the use of carbopol?
binding agent, topical gel formulation, bioadhesives, cream/gel formulation
52
What does eudragit polymer do? | anionic copolymer based on methacrylic acid MA and methylmethacrylate MMA
- Produce gastric resistant film which prevents early disintegration in stomach - but fast release in intestine - coat drugs that cause GI SE
53
What is the coating method for eudragit polymers?
1. eudragit solutions in organic solvents | 2. Coalescence of aqueous powder particles forms a film
54
What is advantage of the lactide homopolymers and copolymers (biodegradable - DL-PLGA)
Biomcampatible, biodegradable, minimal inflmmation, regulatory approved, controllable degradation rate
55
Degradation rate is dependant on
polymer MW, composition (PLA vs PGA), lactide:glycolide ratio, polymer crystallinity (L.PLA-crystal vs DL.PLA-no shape)
56
What is polymer gel?
polymer-solvent system composed of 3D network of polymer chains stabilised by physical and chemical crosslinke
57
How to prepare polymer gel?
1. swell the solid polymer 2. reduce polymer solubility in solvent 3. crosslink the linear polymer chains 4. polymerisation of monomers with crosslinking agent
58
What are the two types of gel?
type 1: irreversible system - covalent bonding (PEG) type 2: reversible (by cooling/heating) - intermolecular bonds like H-bonds, Physical chain entaglements or crystallline units (PVA)
59
What is PVA used for?
gel point = 14degrees for topical delivery system dries quickly to form film
60
Where is alginate (natural polymer gels) extracted from?
cell wall of brown seaweed
61
What is the chemical structure of alginate?
unbranched, block copolymers of 2 different acid components (monomers: D-mannuronic acid (M), L-guluronic acid (G))
62
What is the copolymer structure of alginate?
M block: MMMM G block: GGGG interspersed with hetero block (equal proportion): MGMG
63
How to make alginate?
Crosslinking between alginate chains in solution by interaction between COOH on G, divalent (Ca2+), trivalent (Fe3+) ions M is not reactive
64
Each Ca2+ links the..?
2 alginate chains -->network -->gel
65
Where is alginate polymer used?
- enhance visocity - in-situ gelling for cornea/wound - cell encapsulation for insulin production - bioactive molecule delivery - SR alginate containing diclofenac - Sustained delivery of theophilline from alginate gels oral admin
66
Controlling drug release by using polymers include:
1. rapid polymer dissolution & simultaneous release (CAP) 2. slow drug diffusion by water-insoluble polymer film, dialysis membrane effect (Silicon) 3. Delayed drug diffusion by gel layer formation, swollen polymer (cellulose)
67
what are the mechanisms of drug release from hydrogel?
- physically entangle gels dissolve and release drug - chemically crosslinked gels degrade by hydrolysis/enzymes - drug diffuse from swollen gels

PHRM3021 (3 decks)

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