Lec 15- Polymers in drug delivery Flashcards
1
Q
Polymer
A
- Substances of high molecular weight made up of repeating monomer units
- Can be used to form a diffusion barrier, packaging
- Biodegradable polymers break down in to monomers and then solubles into the monomers
2
Q
Monomer units
A
- Ethylene (CH2=CH2)
- Styrene
- Methylcellulose
3
Q
Polyethylene
A
4
Q
Macro-structure of polymer
A
- Linear
- Branched
- Cross-linked- cross carmellose sodium- can be used as part of the excipients such as this is a disintegrate
5
Q
More structural
A
- Star
- Comb
- Ladder
- Semi-ladder
6
Q
Dendrimer
A
- Highly branched constructs formed from a central core which define their initial geometry
- Tend to be spherical
- NB- small molecule can be trapped in pores within the dendrimer
- Encapsulation of drugs
- Covalently attached targeting moieties
7
Q
Polymer Molecular Architecture
A
- Homopolymer (Single monomer)- A-A-A-A-A-A-A-A
- The copolymer (more than one monomer)
- Alternating copolymer- A-B-A-B-A-B-A-B
- Random co-polymer- AAABBABABBBBAAA
- Block copolymer- AAAAABBBAAAAABBB-
- Graft co-polymer
- Non-linear block- one polymer with another branching from it
8
Q
Combination of arrangements
A
- Star homopolymer
- Star block co-polymer
9
Q
Polydispersity
A
- Small molecules of a given pure compound all have the same molecular weight- Monodisperse
- During synthesis, polymer chain grow at different rates
- The resulting polymer has a range of molecular weights
- Polydisperse or heterodisperse
- Described by an average molecular weight and an molecular weight distribution
10
Q
Two types of molecular weight
A
- Number average molecular weight
- Determined by
- Chemical analysis
- Osmotic pressure
- Determined by
- Weight average molecular weight (Mw)-
- Determined by
- Light scattering technique
- Determined by
11
Q
Number average molecular weight (Mn)
A
- The statistical average molecular weight of all the polymer chains in the sample
*
12
Q
Example question
A
13
Q
Determination of Mn
Number average molecular weight
A
14
Q
Weight average molecular weight
A
- Mw takes into account the molecular weight of a chain in determining contributions to the molecular weight average
15
Q
Weight average molecular weight
Mw
A
- However- Mass= number of moles x MW
- learn the red box
16
Q
Example question
A
17
Q
Degree of Polydispersity
A
- Mw > Mn if the mixture is polydisperse
- If the average molecular weight measured by light scattering techniques is greater than that obtained by osmotic pressure => the mixture is polydisperse
- The ratio Mw/Mn measures the degree of polydispersity
- In our example 1750/1600 = 1.09
- The closer the value is to 1 the higher the mono-dispersity of that polymer
18
Q
Short answer question
A
19
Q
Applications
A
- Packaging
- Tops, Bungs, Containers
- Viscosity modifiers, suspending and emulsifying agents
- Disintergrants- especially cross-linked polymers
- Coating material
- Gels, wound-dressing
20
Q
Applications
Polymeric delivery systems
A
- Membranes and matrices
- Adhesives
- Nano and micro-particles- spray drying can achieve drug encapsulated within the polymer (oil in water- with the drug in the oil phase and polymer in the water)
- Hydrogels- transdermal (often gel structured around the gel- often release can be modified due to the response from the body (such as body temperature))
- Ion exchange resins
21
Q
Synthetic polymer
(Eudragit)
A
- Polymers can be synthesised with pH-dependent solubility (Acidic moieties) or viscosity, biodegradability or membrane-forming characteristics
- If biodegradable
- Need to consider the safety of degradation products- often use lactic acid (lactic acid is a natural product from the body)
- Kinetics of degradation may need careful control
22
Q
Natural polymers
A
- Vary in purity
- Often require cross-linking to control the release
- Polypeptides and proteins
- Albumin, gelatin
- Polysaccharides
- Starch, Chitosan
- Polypeptides and proteins
- Purity can be a problem
- Natural often have microbiological contamination
23
Q
Controlled-release mechanisms (systems)
A
- Diffusion
- Reservoir systems
- Monolithic systems
- Swelling systems
- Osmotic systems
- Biodegradable systems
- Mechanical pumps
24
Q
Controlled release mechanisms
A
- Any or all of these mechanisms can occur in a given release system
- Diffusion
- Swelling followed by diffusion
- Degradation
- For controlled drug delivery formulations, a material must be chemically inert and free of leachable impurities
- Must have an appropriate physical structure with minimal undesired ageing and be readily processable
25
Q
Biodegradable polymers
A
- These materials degrade by natural biological processes, eliminating the need to remove the finished delivery system
- (A) Represent BULK-ERODING- sponge
- Parts of the polymer are biodegraded, leaving gaps for the drug to be released
- (B) Represent SURFACE-ERODING- onion
- Layer by layer lost from the surface
- This will achieve a more constant release profile- as the layers will degrade at the same rate allowing a consistent drug release
- (A) Represent BULK-ERODING- sponge
26
Q
Biodegradable polymers
Different polymers degrade at different rates within the body and therefore polymer selection can be tailored to achieve desired release rate
Factors effecting degradation
A
- Degradation can be affected by a wide range of factors
- Structure and composition
- Physical and physicochemical factors-
- Purity
- Presence of ionic groups
- Presence of low MW compounds
- MW and distribution
- Morphology
- Processing conditions
- Sterilisation process and storage history
- Shape
- Site of implantation
27
Q
Polylactide and polylactide-co-glycolide
A
- Polymers of lactic acids and glycolic acid
- Homopolymer (usually lactide PLA)
- Co-polymer (PLGA)
28
Q
Current market for PLGA formulations
A
- PLA and PLGA
- Undergo hydrolysis from biologically compatible and metabolisable moieties
- Currently used as suture, bone implants (as bone regenerates the polymer disintegrates) and screws and depot formulations
- Marketed depot formulations include microparticles containing octreodide (sandostatin LAR) and Risperdal Consta
29
Q
PLGA as a polymer for drug delivery
A
- Advantages
- Long safe history
- Biodegrades to natural metabolites
- Control of degradation
- MW- change MW with different grades
- Polymer composition (copolymer ratio)
- Hydrophobicity, crystallinity, glass transition as well as release profile
- Particle size, shape, morphology and loading
30
Q
PLGA degradation
A
- Bulk erosion is the main degradation pathway for PLGA
- Random scission of ester bonds proceeding homogeneously through polymer backbone
- Three phase mechanism proposed
- Initial rapid decrease in MW with no soluble monomer formation
- Decrease in MW with rapid mass loss and formation of soluble products
- Formation of soluble monomers resulting in complete polymer degradation
- Incorporated drugs have the potential to modify degradation rates
31
Q
Surface-Eroding systems
A
- Polyanhydrides as biodegradable polymers for drug delivery (surface eroding)
- Matrices can degrade over periods ranging from 1 day to many months and any times in between
- Degradation is through surfaceErosion, leading to ZERO ORDER release
- Marketed product- Gliadel wafers
32
Q
Cellulose derivatives
A
- Polysaccharides formulated into hydrophilic matrices
- Popular biomaterial
- MW and particle size can influence release from these matrices along with polymer relaxation
- HPMC
- HEC
- HPC
- MCC
33
Q
A
