POLYMER SCIENCE

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POLYMER SCIENCE

• By
• Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph.D
• KLE Universitys College of Pharmacy
• BELGAUM -590010, Karnataka, India
• Cell 00919742431000
• Cell No bknanjwade_at_yahoo.co.in

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CONTENTS

• INTRODUCTION TO POLYMERS
• CLASSIFICATION OF POLYMERS
• GENERAL MECHANISM OF DRUG RELEASE
• APPLICATION IN CONVENTIONAL DOSGAE FORMS
• APPLICATIONS IN CONTROLLED DRUG DELIVERY
• BIODEGRADABLE POLYMERS
• NATURAL POLYMERS
• REFERENCESS

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INTRODUCTION

• A polymer is a very large molecule in which one
  or two small units is repeated over and over
  again
• The small repeating units are known as
  monomers
• Imagine that a monomer can be represented by
  the letter A. Then a polymer made of that monomer
  would have the structure
• -A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-
  A-A-A

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• In another kind of polymer, two different
  monomers might be involved
• If the letters A and B represent those
  monomers, then the polymer could be represented
  as
• -A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-
  B-A-B-A
• A polymer with two different monomers is
  known as a copolymer.

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Chemistry of the polymers

• Polymers are organic, chain molecules
• They can, vary from a few hundreds to thousands
  of atoms long.
• There are three classes of polymers that we will
  consider-
• Thermo-plastic - Flexible linear chains
• Thermosetting - Rigid 3-D network
• Elastomeric - Linear cross-linked chains

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THERMOPLASTICS

• In simple thermoplastic polymers, the chains are
  bound to each other by weaker Van der Waals
  forces and mechanical entanglement.
• Therefore, the chains are relatively strong, but
  it is relatively easy to slide and rotate the
  chains over each other.

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ELASTOMERS

• Common elastomers are made from highly coiled,
  linear polymer chains.
• In their natural condition, elastomers behave in
  a similar manner to thermoplastics (viscoelastic)
• i.e. applying a force causes the chains to
  uncoil and stretch, but they also slide past each
  other causing permanent deformation.
• This can be prevented by cross-linking the
  polymer chains

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• Polymers can be represented by
• 3-D solid models
• 3-D space models
• 2-D models

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MOLECULAR STRUCTURE

• The mechanical properties are also governed by
  the structure of the polymer chains.
• They can be
• Linear
  Network (3D)
• Branched
• Cross-linked

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POLYMER MOLECULES

• Before we discuss how the polymer chain molecules
  are formed, we need to cover some definitions
• The ethylene monomer looks like
• The polyethylene molecule looks like

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• Polyethylene is built up from repeat units or
  mers.
• Ethylene has an unsaturated bond. (the double
  bond can be broken to form two single bonds)
• The functionality of a repeat unit is the number
  of sites at which new molecules can be attached.

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MOLECULAR WEIGHT

• When polymers are fabricated, there will always
  be a distribution of chain lengths.
• The properties of polymers depend heavily on the
  molecule length.
• There are two ways to calculate the average
  molecular weight
• 1 Number Average Molecular Weight
• 2. Weight Average Molecular Weight

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• Number Average Molecular Weight
• Mn S Xi Mi
• Where, xi number of chains in the ith weight
  range
• Mi the middle of the ith weight
  range
• Weight Average Molecular Weight
• Mw S Wi Mi
• Where, wi weight fraction of chains in the ith
  range
• Mi the middle of the ith weight
  range

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MOLECULAR SHAPE

• The mechanical properties of a polymer are
  dictated in part by the shape of the chain.
• Although we often represent polymer chains as
  being straight,
• They rarely are.

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Contd

• The carbon carbon bonds in simple polymers form
  angles of 109º

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POLYMER CRYSTALLINITY

• Thermoplastic polymers go through a series of
  changes with changes in temperature. (Similar to
  ceramic glasses)
• In their solid form they can be semi-crystalline
  or amorphous (glassy).

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CRYSTALLINE THERMOPLASTIC

• The ability of a polymer to crystallize is
  affected by
• Complexity of the chain Crystallization is
  easiest for simple polymers (e.g. polyethylene)
  and harder for complex polymers (e.g. with large
  side groups, branches, etc.)
• Cooling rate Slow cooling allows more time for
  the chains to align
• Annealing Heating to just below the melting
  temperature can allow chains to align and form
  crystals
• Degree of Polymerization It is harder to
  crystallize longer chains
• 5. Deformation Slow deformation between Tg and
  Tm can straighten the chains allowing them to get
  closer together.

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• CLASSIFICATION POLYMERS
• ON BASIS OF INTERACTION WITH WATER
• Non-biodegradable hydrophobic Polymers
• E.g. polyvinyl chloride, polyethylene vinyl
  acetate
• Soluble Polymers E.g. HPMC, PEG
• Hydrogels E.g. Polyvinyl
  pyrrolidine
• BASED ON POLYMERISATION METHOD
• Addition Polymers E.g. Alkane Polymers
• Condensation polymers E.g. Polysterene and
  Polyamide
• Rearrangement polymers
• BASED ON POLYMERIZATION MECHANISM
• Chain Polymerization
• Step growth Polymerization

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Contd.

• BASED ON CHEMICAL STRUCTURE
• Activated C-C Polymer
• Polyamides, polyurethanes
• Polyesters, polycarbonates
• Polyacetals, Polyketals, Polyorthoesters
• Inorganic polymers
• Natural polymers
• BASED ON OCCURRENCE
• Natural polymers E.g. 1. Proteins-collagen,
  keratin, albumin, 2. carbohydrates- starch,
  cellulose
• Synthetic polymers E.g. Polyesters, polyamides

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Contd.

• BASED ON BIO-STABILITY
• Bio-degradable
• Non Bio-degradable

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CHARACTERISTICS OF AN IDEAL POLYMER

• Should be versatile and possess a wide range of
  mechanical, physical, chemical properties
• Should be non-toxic and have good mechanical
  strength and should be easily administered
• Should be inexpensive
• Should be easy to fabricate
• Should be inert to host tissue and compatible
  with environment

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CRITERIA FOLLOWED IN POLYMER SELECTION

• The polymer should be soluble and easy to
  synthesis
• It should have finite molecular weight
• It should be compatible with biological
  environment
• It should be biodegradable
• It should provide good drug polymer linkage

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GENERAL MECHANISM OF DRUG RELEASE FROM POLYMER

• There are three primary mechanisms by which
  active agents can be released from a delivery
  system namely,
• Diffusion, degradation, and swelling followed by
  diffusion
• Any or all of these mechanisms may occur in a
  given release system
• Diffusion occurs when a drug or other active
  agent passes through the polymer that forms the
  controlled-release device. The diffusion can
  occur on a macroscopic scale as through pores in
  the polymer matrix or on a molecular level, by
  passing between polymer chains

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Drug release from typical matrix release system
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• For the reservoir systems the drug delivery rate
  can remain fairly constant.
• In this design, a reservoir whether solid drug,
  dilute solution, or highly concentrated drug
  solution within a polymer matrix is surrounded by
  a film or membrane of a rate-controlling
  material.
• The only structure effectively limiting the
  release of the drug is the polymer layer
  surrounding the reservoir.
• This polymer coating is uniform and of a
  nonchanging thickness, the diffusion rate of the
  active agent can be kept fairly stable throughout
  the lifetime of the delivery system. The system
  shown in Figure a is representative of an
  implantable or oral reservoir delivery system,
  whereas the system shown in b.

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                                     Drug
delivery from typical reservoir devices (a)
implantable or oral systems, and (b) transdermal
systems.

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ENVIRONMENTALLY RESPONSIVE SYSTEM

• It is also possible for a drug delivery system to
  be designed so that it is incapable of releasing
  its agent or agents until it is placed in an
  appropriate biological environment.
• Controlled release systems are initially dry and,
  when placed in the body, will absorb water or
  other body fluids and swell,
• The swelling increases the aqueous solvent
  content within the formulation as well as the
  polymer mesh size, enabling the drug to diffuse
  through the swollen network into the external
  environment.

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• Examples of these types of devices are shown in
  Figures a and b for reservoir and matrix systems.
• Most of the materials used in swelling-controlled
  release systems are based on hydrogels, which are
  polymers that will swell without dissolving when
  placed in water or other biological fluids. These
  hydrogels can absorb a great deal of fluid and,
  at equilibrium, typically comprise 6090 fluid
  and only 1030 polymer.

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Drug delivery from (a) reservoir and (b) matrix
swelling-controlled release systems.
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APPLICATIONS

• The pharmaceutical applications of polymers
  range from their use as binders in tablets
• Viscosity and flow controlling agents in liquids,
  suspensions and emulsions
• Polymers are also used as film coatings to
  disguise the unpleasant taste of a drug, to
  enhance drug stability and to modify drug release
  characteristics.

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Applications in Conventional Dosage Forms

• Tablets
• - As binders
• - To mask unpleasant taste
• - For enteric coated tablets
• Liquids
• - Viscosity enhancers
• - For controlling the flow
• Semisolids
• - In the gel preparation
• - In ointments
• In transdermal Patches

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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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• BIO DEGARADABLE POLYMERS

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BIO DEGRADABLE POLYMER

• 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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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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CONTD

• 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
DELEVERY

• Localized delivery of drug
• Sustained delivery of drug
• Stabilization of drug
• Decrease in dosing frequency
• Reduce side effects
• Improved patient compliance
• Controllable degradation rate

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ROLE OF POLYMER IN DRUG DELIVERY

• 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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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 suture
  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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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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Schematic representation of drug release
mechanisms In mechanism 1, drug is released by
hydrolysis of polymeric bond. In mechanism 2,
drug release is controlled by biodegradable
membrane. In mechanism 3, drug is released by
erosion, diffusion, or a combination of both
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POLYMER EROSION MECHANISM

• The term 'biodegradation' is limited to the
  description of chemical processes (chemical
  changes that alter either the molecular weight or
  solubility of the polymer)
• Bioerosion' may be restricted to refer to
  physical processes that result in weight loss of
  a polymer device.
• The erosion of polymers basically takes place by
  two methods-
• Chemical erosion
• Physical erosion

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CHEMICAL EROSION

• There are three general chemical mechanisms that
  cause bioerosion
• The degradation of water-soluble macromolecules
  that are crosslinked to form three-dimensional
  network.
• As long as crosslinks remain intact, the
  network is intact and is insoluble.
• Degradation in these systems can occur
  either at crosslinks to form soluble backbone
  polymeric chains (type IA) or at the main chain
  to form water-soluble fragments (type IB).
  Generally, degradation of type IA polymers
  provide high molecular weight, water-soluble
  fragments, while degradation of type IB polymers
  provide low molecular weight, water soluble
  oligomers and monomers

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• The dissolution of water-insoluble macromolecules
  with side groups that are converted to
  water-soluble polymers as a result of ionization,
  protonation or hydrolysis of the groups. With
  this mechanism the polymer does not degrade and
  its molecular weight remains essentially
  unchanged. E.g. cellulose acetate
• The degradation of insoluble polymers with labile
  bonds. Hydrolysis of labile bonds causes scission
  of the polymer backbone, thereby forming low
  molecular weight, water-soluble molecules. E.g.
  poly (lactic acid), poly (glycolic acid)
• The three mechanisms described are not
  mutually exclusive combinations of them can
  occur.

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PHYSICAL EROSION

• The physical erosion mechanisms can be
  characterized as heterogeneous or homogeneous.
• In heterogeneous erosion, also called as surface
  erosion, the polymer erodes only at the surface,
  and maintains its physical integrity as it
  degrades. As a result drug kinetics are
  predictable, and zero order release kinetics can
  be obtained by applying the appropriate geometry.
  Crystalline regions exclude water. Therefore
  highly crystalline polymers tend to undergo
  heterogeneous erosion. E.g polyanhydrides

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• Homogeneous erosion, means the hydrolysis occurs
  at even rate throughout the polymeric matrix.
  Generally these polymers tend to be more
  hydrophilic than those exhibiting surface
  erosion. As a result, water penetrates the
  polymeric matrix and increases the rate of
  diffusion. In homogeneous erosion, there is loss
  of integrity of the polymer matrix. E.g poly
  lactic acid

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• Natural polymers
• Polymers are very common in nature
• some of the most widespread naturally occurring
  substances are polymers Starch and cellulose are
  examples
• Green plants have the ability to take the simple
  sugar known as glucose and make very long chains
  containing many glucose units
• These long chains are molecules of starch or
  cellulose
• If we assign the symbol G to stand for a
  glucose molecule, then starch or cellulose can be
  represented as
• -G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G
  -G-G-

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NATURAL POLYMERS

• Natural polymers remains the primary choice of
  formulator because
• - They are natural products of living organism
• - Readily available
• - Relatively inexpensive
• - Capable of chemical modification
• Moreover, it satisfies most of the ideal
  requirements of polymers.
• But the only and major difficulty is the batch-
  to-batch reproducibility and purity of the sample.

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• Examples
• 1) Proteins
• - Collagen Found from animal tissue.
• Used in absorbable sutures, sponge wound
  dressing, as drug delivery vehicles
• - Albumin Obtained by fabrication of blood
  from healthy donor.
• Used as carriers in nanocapsules
  microspheres
• - Gelatin A natural water soluble polymer
• Used in capsule shells and also as coating
  material in microencapsulation.

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• 2) Polysaccharides
• - Starch Usually derivatised by introducing
  acrylic
• groups before manufactured int
  microspheres.
• Also used as binders.
• - Cellulose
• Naturally occuring linear polysaccharide. It
  is insoluble in water but solubility can be
  obtained by substituting -OH group.
• Na-CMC is used as thickner, suspending
  agent, and film formers.
• 3) DNA RNA
• They are the structural unit of our body. DNA
  is the blueprint that determines everything of
  our body.

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CURRENTLY AVAILABLE POLYMERS FOR CONTROLLED
RELEASE

• Diffusion controlled systems
• Solvent activated systems
• Chemically controlled systems
• Magnetically controlled systems

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DIFFUSION CONTROLLED SYSTEM 

• Reservoir type
• Shape spherical, cylindrical, disk-like
• Core powdered or liquid forms
• Properties of the drug and the polymer
  diffusion rate and release rate into the
  bloodstream
• Problems removal of the system, accidental
  rupture
• Matrix type
• Uniform distribution and uniform release rate
• No danger of drug dumping

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SOLVENT ACTIVATED SYSTEM

• Osmotically controlled system
• Semipermeable membrane
• Osmotic pressure decrease concentration gradient
• Inward movement of fluid out of the device
  through a small orifice
• Swelling controlled system
• Hydrophilic macromolecules cross-linked to form a
  three-dimensional network
• Permeability for solute at a controlled rate as
  the polymer swells
•  

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CHEMICALLY CONTROLLED SYSTEMS

• Pendant-chain system
• Drug chemically linked to the backbone
• Chemical hydrolysis or enzymatic cleavage
• Linked directly or via a spacer group
• Bioerodable or biodegradable system
• Drug uniformly dispersed
• Slow released as the polymer disintegrates
• No removal from the body
• Irrespective of solubility of drug in water
•   

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MAGNETICALLY CONTROLLED SYSTEMS

• Cancer chemotherapy
• Selective targeting of antitumor agents
• Minimizing toxicity
• Magnetically responsive drug carrier systems
• Albumin and magnetic microspheres
• High efficiency for in vivo targeting
• Controllable release of drug at the microvascular
  level
•   

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RECENTLY DEVELOPED MARKETED FORMULATIONS

• Medisorb
• Microencapsulation by PLA, PGA, PLGA
• Drug release week to one year
• Alzamer
• Bioerodible polymer release at a
  controlled rate
• Chronic disease, contraception, topical
  therapy

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USE OF FEW POLYMERS IN DRUG DELIVERY

• Poly(L-lactic acid) for release of progesterone,
  estradiol, dexamethasone
• Copolymer of gluconic acid and ethyl-L-glutamte
  as bioerodible monolithic device
• PLA, PGA, PLGA for parenteral administration of
  polypeptide
• Sustained release (weeks or months)
•  Orahesive sodium carboxymethyl cellulose,
  Pectin, gelatin
• Orabase blend in a polymethylene/mineral oil
  base  

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REFERENCES

• Novel drug delivery systems Y.W.Chien Dekker
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• Bioadhesive drug delivery system
• Dekker 98
• Encyclopedia of controlled drug delivery systems.
• www.google.com

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ANY QUERIES?
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Y
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Cell No 00919742431000 E-mailbknanjwade_at_yahoo.co
.in
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