Polymers in CDDS
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INTRODUCTION
• Polymers are used extensively in our daily
routine life.
• In pharmaceutical preparations also they
have several applications
e.g. In mfg of bottles, syringes, vials,
cathaters, and also in drug formulations.
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What is Polymer?
• “Polymer” word is derived from Greek roots
“Poly” meaning many and “Meros” meaning
parts.
• Definition :
Polymers are long chain organic molecules
assembled from many smaller molecules called
as monomers.
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• Copolymer :
Polymers formed from two or more
different monomers are called as
copolymers.
– [A – B – A – B – A – B] –
• Homopolymer :
Polymers formed from bonding of
identical monomers are called as
homopolymers.
– [A – A – A – A – A] –
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CLASSIFICATION
A. Based on origin :
a) Natural Polymers :
e.g. Proteins – Collagen, Keratin, Albumin
Carbohydrates – starch, cellulose,
glycogen.
DNA, RNA
b) Synthetic Polymers :
e.g. polyesters, polyanhydrides, polyamides.
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B. Based on Bio-stability :
a) Bio-degradable Polymers :
e.g. polyesters, proteins,
carbohydrates, etc
b) Non – biodegradable Polymers :
e.g. ethyl cellulose, HPMC, acrylic
polymers, silicones.
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C. Based on Reaction mode of Polymerization :
a) Addition Polymers :
Here, the monomer molecules bond to
each other without the loss of any other
atoms.
e.g. Alkene monomers
b) Condensation Polymers :
Usually two different monomers combine
with the loss of small molecule, usually water.
e.g. polyesters, polyamides.
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D. Based on Interaction with Water :
a) Non – biodegradable Hydrophobic Polymers :
These are inert compounds and are eliminated
intact from the site of application.
e.g. polyethylene – vinyl acetate, polyvinyl chloride.
b) Hydrogels :
They swell but do not dissolve when brought in
contact with water.
e.g. polyvinyl pyrrolidone
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c) Soluble Polymers :
These are moderate mol. wt uncross-linked
polymers that dissolve in water.
e.g. HPMC, PEG
d) Biodegradable Polymers :
These slowly disappear from the site of
administration in response to a chemical reaction such
as hydrolysis.
e.g. Polyacrylic acid. Polyglycolic acid.
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Ideal Characteristics of polymer for its
selection
• Should be inert and compatible with the environment.
• Should be non-toxic.
• Should be easily administered.
• Should be easy and inexpensive to fabricate.
• Should have good mechanical strength.
• Characteristics Predictability of biodegradation kinetics
• Ease of fabrication / processability
• Their toxicity / antigenicity / anti-inflammatory profile following
erosion
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• Absence of toxic endogenous impurities or residual
chemicals used in their preparation,
• e.g. cross-linking agents
• Achieve controlled heterogenous erosion without any
additive
• Acceptable shelf-life
• Ability to withstand sterilization procedures
• Degradation products that are excreted readily
• Regulatory approval
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– It must be soluble and easy to synthesize; must
have a finite molecular wt.
– Should provide drug attachment and release
sites for drug polymer linkages.
– Should be compatible with biological
environment, i.e. non-toxic and non-antigenic.
– Should be biodegradable or be eliminated from
body after its function is over.
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PROPERTIES & SELECTION OF
POLYMERS
POLYMER IS CHOOSEN ON BASIS OF :-
• Physicochemical properties
• Need for biochemical characters.
• Chemical composition
• Micro structural design
• Surface properties like lubricity, hydrophilicity, smoothness,
surface energy
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PROPERTIES OF SYNTHETIC POLYMER THAT NEED TO BE CONSIDERD
FOR APPLICATION OF POLYMERS TO DRUG DELIVERY SYSTEMS
• Solubility
• Viscosity
• Polymer- Solvent interaction
• Crystallinity
• Polymer dissolution
• Bioadhesivity of Hydrophilic polymer
• Polymer erosion & Biodegradation
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Molecular weight
• In polymer synthesis, polymer is produced with a
distribution of molecular weights
• Linear polymers used in biomedical applications
generally have a number average molecular weight
in the range of 25,000 to 100,000 and weight
average molecular weight from 50,000 to 30,000
• Increasing molecular weight corresponds to
increasing physical properties
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Tacticity
Arrangement of substituents around the
extended polymer chain
• Isotactic – chains located on the same side of zig-zag chain
• Syndiotactic – chains have substituents alternating from side
to side
• Atactic – substituents appear at random on either side of
chain
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Crystallinity
– Polymers either amorphous or semicrystalline,
never completely crystalline
– Tendency of polymer to crystallize enhanced by
small side groups and chain regularity.
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Mechanical properties
–Ultimate mechanical properties of polymers
at large deformations important in selecting
polymers for biomedical applications
–Ultimate strength – stress at or near failure
–Fatigue behavior – how a polymer
withstands cycles of stress and release
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Thermal properties
Tg – temperature at which all long-range segmental
polymeric motion ceases
•Varies from polymer to polymer
• Polymers used below Tg tend to be hard and glassy and
above Tg tend to be rubbery
• Tg always below Tm
• Target region for biomedical applications is rubbery
plateau region above Tg where long-range segmental
motion is occurring.
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• Crystalline polymers tend to be tough and ductile
• Chemically cross-linked polymers exhibit modulus
versus temperature behavior analogous to that of
linear amorphous polymers, until flow regime is
approached.
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Applications In Controlled Drug
Delivery
• Reservoir Systems
– Ocusert System
– Progestasert System
– Reservoir Designed Transdermal Patches
• Matrix Systems
• Swelling Controlled Release Systems
• Biodegradable Systems
• Osmotically controlled Drug Delivery
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A. Reservoir Systems –
Consists of core reservoir of drug sandwiched
between sheets of rate controlling membrane
of polymer.
e.g. Ocusert System
– Progestasert System
– Reservoir Designed Transdermal Patches
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Drug is sandwiched between drug impermeable
backing and drug permeable rate controlling
polymer.
e.g. Ethylene-vinyl acetate copolymer
In the reservoir, drug is dispersed in solid polymer matrix.
e.g. Polyisobutylene
On the external surface, there should be adhesive
polymer. e.g. Silicone Polymer, Polyacrylates.
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B. Matrix Systems
• Drug particles are enclosed in a matrix
environment formed by cross-linking of polymer
chains.
• For the drug to get released, it has to be first
dissolved in surrounding polymer and then
diffuse through the polymer structure.
• Polymers used are :
polyalkyls, polyvinyls, etc.
• Example – Nitroglycerine releasing system for
prophylaxis or treatment of angina pectoris.
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C. Swelling Controlled Release
Systems
• Drug is enclosed in a collapsible drug compartment
inside a rigid, shape-retaining housing.
• The shape between external housing and drug
compartment contains laminate of swellable,
hydrophillic cross-linked polymer.
e.g. polyhydroxyalkyl methacrylate.
• This polymer absorbs GI fluid through annular
openings in the bottom of housing.
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D. Biodegradable System
• Mainly used for parenteral controlled drug
delivery.
• Drug is encapsulated in biodegradable
microcapsules which are suspended in
aqueous / oleaginous medium and injected
subcutaneously or intra-muscularly.
• Polymers used for microcapsules are :
Gelatin, dextran, polylactate, lactide –glycolide
copolymer.
• The release of drug is controlled by the rate of
bio-degradation of polymer.
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E. Osmotically Controlled Drug
Delivery System
• Drug is coated with semi-
permeable polymer
e.g. Cellulose acetate.
• Water generates osmotic
pressure gradient by
permeating through semi-
permeable membrane.
• Due to that drug pumps
out of delivery orifice over
a prolonged time at a
defined rate.
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BIO DEGARADABLE POLYMERS
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BIO DEGRADABLE POLYMER
• Polymers that degrade within the body as a result of natural biological
processes, are called biodegradable polymers.
• Biodegradable polymers can be classified in two:
• Natural biodegradable polymer
• Synthetic biodegradable polymer
• Synthetic biodegradable polymer are preferred more than the natural
biodegradable polymer because they are free of immunogenicity & their
physicochemical properties are more predictable & reproducible.
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Ideal characteristics of Biodegradable
polymer
• They should be biocompatible-(shape, surface, and leachable)
• They should be bio absorbable-(degradability profile,
reabsorption of degradation products.)
• They should be bifunctional-(physical, mechanical and
biological).
• They should be stable-(processing, sterilization and storage).
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CLASSIFICATION OF BIODEGRADABLE
POLYMERS:
• Natural polymers:
Proteins: Example: Albumin, Collagen, Gelatin etc.
Polysaccharides: Example: Sodium alginate, Chitin,
Chitosan, Cellulose, Dextran, Insulin, Hyaluronic acid,
Starch
•Synthetic polymers:
Aliphatic polyesters: Example: Poly-Glycolic Acid (PGA),
Poly Lactic Acid (PLA), Poly-Hydroxy Butyrate (PHB), Poly-
β-Malic Acid (PMA) etc.
Poly Phospho Esters Poly Anhydrides Poly Phosphazenes
Pseudo Amino Acids Poly Ortho Esters
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NATURAL POLYMERS:-
• The use of natural biodegradable polymers to deliver drugs
continues to be an area of active research despite the
advent of synthetic biodegradable polymers.
Natural polymers remain attractive primarily because,
• They are an attractive class of biodegradable polymers.
• They are derived from natural sources.
• They are easily available.
• They are relatively cheap.
• They qualify for a number of chemical modifications.
• They can be a protein or a polysaccharide in chemical
origin.
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• Modified natural polymers are natural polymers
altered to improve their biodegradation profile
that can be achieved by chemical modifications
or enzymatic alteration.
• Examples: Proteins: •Albumin •Collagen •Gelatin
ALBUMIN:
• It is a major plasma protein component.
• It accounts for more than 55% of total protein in
human plasma.
• It is used to design particulate drug delivery
systems.
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• Synthetic polymers:
• Most attractive class of polymers.
• Biocompatible and versatile in terms of
physical, chemical and biological properties.
• Examples:
Aliphatic polyesters: PGA, PLA etc.
poly Phospho Esters (PPE)
Poly Ortho Esters (POE), etc.
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FACTORS AFFECTING BIODEGRADATION OF POLYMERS
• PHYSICAL FACTORS
• Shape & size
• Variation of diffusion coefficient
• Mechanical stresses
• CHEMICAL FACTORS
• Chemical structure & composition
• Presence of ionic group
• Distribution of repeat units in multimers
• configuration structure
• Molecular weight
• Morphology
• Presence of low molecular weight compounds
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• Processing condition
• Annealing
• Site of implantation
• Sterilization process
• PHYSICOCHEMICAL FACTORS
• Ion exchange
• Ionic strength
• pH
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Advantages of Biodegradable Polymers In Drug Delivery
• provides a drug at a constant controlled rate owes a prescribed
period of time.
• Localized delivery of drug
• Sustained delivery of drug
• Stabilization of drug
• Decrease in dosing frequency
• Reduce side effects
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• Improved patient compliance
• The polymer carrier would degrade into nontoxic, absorbable subunits which
would be subsequently metabolized.
• Controllable degradation rate
• The system would be biocompatible would not exhibit dose dumping at any
time and polymer would retain its characteristics until after depletion of the
drug.
• Degradable system eliminates the necessity for surgical removal of implanted
device following depletion of a drug.
• They are broken down into biologically acceptable molecules that are
metabolized
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Disadvantage
1. Sometimes the degradable polymers exhibit substantial dose
dumping at some point following implantations.
2. A “burst effect” or high initial drug release soon after
administration is typical of most system.
3. Degradable systems which are administered by injection of a
particulate form are non-retrievable
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DRUG RELEASE MECHANISM
• The release of drugs from the erodible polymers occurs basically by
three mechanisms,
• The drug is attached to the polymeric backbone by a labile bond, this
bond has a higher reactivity toward hydrolysis than the polymer
reactivity to break down.
• The drug is in the core surrounded by a biodegradable rate controlling
membrane. This is a reservoir type device that provides erodibility to
eliminate surgical removal of the drug-depleted device.
• A homogeneously dispersed drug in the biodegradable polymer. The
drug is released by erosion, diffusion, or a combination of both.
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Bio Degradable Polymers for Advance Drug Delivery
– Polymers play an vital role in both conventional as well as
novel drug delivery. Among them , the use of bio degradable
polymer has been success fully carried out.
• Early studies on the use of biodegradable sutures demonstrated
that these polymers were non- toxic & biodegradable.
• By incorporating drug into biodegradable polymer whether
natural or synthetic, dosage forms that release the drug in
predesigned manner over prolong time
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The polymer can protect the drug from the physiological environment &
hence improve its stability in vivo.
Most biodegradable polymer are designed to degrade within the body as
a result of hydrolysis of polymer chain into biologically acceptable &
progressively small compounds.
TYPES OF POLYMER DRUG DELIVERY SYSTEM:
MICRO PARTICLES: These have been used to deliver therapeutic agents
like doxycycline.
NANO PARTICLES: delivery drugs like doxorubicin, cyclosporine, paclitaxel,
5- fluorouracil etc
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• POLYMERIC MICELLES: used to deliver therapeutic agents.
• HYDRO GELS: these are currently studies as controlled release
carriers of proteins & peptides.
• POLYMER MORPHOLOGY:
The polymer matrix can be formulated as either micro/nano-
spheres, gel, film or an extruded shape.
The shape of polymer can be important in drug release kinetics.
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Application
• For specific site drug delivery- anti tumour agent
• Polymer system for gene therapy
• Bio degradable polymer for ocular, non- viral DNA, tissue
engineering, vascular, orthopaedic, skin adhesive & surgical
glues.
• Bio degradable drug system for therapeutic agents such as anti
tumor, antipsychotic agent, anti-inflammatory agent and
biomacro molecules such as proteins, peptides and nucleic
acids
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