Polymers are large molecules composed of many repeating structural units called monomers. There are two main types of polymerization: addition polymerization and condensation polymerization. Polymers can be classified in several ways, including by source (natural vs synthetic), structure (linear, branched, cross-linked), and molecular forces (elastomers, thermoplastics, thermosets, fibers). Common polymers used in pharmaceutical applications include cellulose, collagen, starches, polycaprolactone, and polymers used in controlled drug release formulations. Polymers can be synthesized via different polymerization methods like bulk, solution, suspension, emulsion, and their reverse phase counterparts.

1. POLYMERS

2. INTRODUCTION
• The word “polymer” means “many parts.” A polymer is a
large molecule made up of many small repeating units.
• In the early days of polymer synthesis, little was known
about the chemical structures of polymers.
• Herman Staudinger, who received the Nobel Prize in
Chemistry in 1953, coined the term “macromolecule” in 1922
and used it in reference to polymers.
• The difference between the two is that polymers are made of
repeating units, whereas the term macromolecule refers to
any large molecule, not necessarily those made of repeating
units. So, polymers are considered to be a subset of
macromolecules

3. • The word “Polymer” is derived from two Greek words, ‘Poly’
that means many (numerous) and ‘Mer’ which means units. In
basic terms, a polymer is a long-chain molecule that is
composed of a large number of repeating units of identical
structure. These identical structures, we understand as a unit
made up of two or more molecules, join together to form a
long chain
• Simply stated, a polymer is a long-chain molecule that is
composed of a large number of repeating units of identical
structure.

4. • A monomer is a small molecule that combines with other molecules
of the same or different types to form a polymer. Since drawing a
complete structure of a polymer is almost impossible, the structure
of a polymer is displayed by showing the repeating unit (the
monomer residue) and an “n” number that shows how many
monomers are participating in the reaction.
• From the structural perspective, monomers are generally classified
as olefinic (containing double bond) and functional (containing
reactive functional groups) for which different polymerization
methods are utilized.

5. • If two, three, four, or five
monomers are attached to each
other, the product is known as a
dimer, trimer, tetramer, or
pentamer, respectively.
• An oligomer contains from 30
to 100 monomeric units.
• Products containing more than
200 monomers are simply
called a polymer.
From a thermodynamic perspective, polymers cannot exist in the gaseous state
because of their high molecular weight. They exist only as liquids or high solid
materials

6. CLASSIFICATION OF POLYMERS
Since Polymers are numerous in number with different
behaviours and can be naturally found or synthetically created,
they can be classified in various ways.
The following below are some basic ways in which we classify
polymers:
I. Classification based on source
II. Classification based on structure
III. Classification based on polymerisation
IV. Classification based on molecular force

7. Classification Based on Source
The first classification of polymers is based on their source of origin
• Natural polymers
• The easiest way to classify polymers is their source of origin. Natural
polymers are polymers which occur in nature and are existing in
natural sources like plants and animals. Some common examples
are Proteins (which are found in humans and animals alike), Cellulose and
Starch (which are found in plants) or Rubber (which we harvest from the latex
of a tropical plant).
• Synthetic polymers
• Synthetic polymers are polymers, which humans can artificially
create/synthesize in a lab. These are commercially produced by industries for
human necessities. Some commonly produced polymers which we use day to
day are Polyethylene (a mass-produced plastic which we use in packaging)
• Semi-Synthetic polymers
• Semi-Synthetic polymers are polymers obtained by making modification in
natural polymers artificially in a lab. These polymers formed by chemical
reaction (in a controlled environment) and are of commercial importance.
Example: Vulcanized Rubber (Sulphur is used in cross bonding the polymer
chains found in natural rubber) and Cellulose derivatives such as cellulose
acetate (rayon) and cellulose nitrate etc.

8. Classification Based on Structure of Polymers
Classification of polymers based on their structure can be of three types:
• Linear polymers:
• These polymers are similar in structure to a long straight chain, which identical
links connected to each other. The monomers in these are linked together to form
a long chain. These polymers have high melting points and are of higher density.
A common example of this is PVC (Poly-vinyl chloride). This polymer is largely
used for making electric cables and pipes.

9. • Branch chain polymers:
• The structure of these polymers is like branches originating at random
points from a single linear chain. Monomers join together to form a long
straight chain with some branched chains of different lengths. As a result
of these branches, the polymers are not closely packed together. They are
of low density having low melting points. Low-density polyethene
(LDPE) used in plastic bags and general purpose containers is a common
example

10. • Cross-linked or Network polymers:
• In this type of polymers, monomers are linked together to form a three-
dimensional network. The monomers contain strong covalent bonds as they
are composed of bi-functional and tri-functional in nature. These polymers
are brittle and hard.
• Examples :- Bakelite (used in electrical insulators), Melamine etc.

11. • Based on Mode of Polymerisation
Polymerization is the process by which monomer molecules are reacted
together in a chemical reaction to form a polymer chain (or three-
dimensional networks).
Based on the type of polymerization, polymers can be classified as:
• Addition polymers:
• These type of polymers are formed by the repeated addition of monomer
molecules. The polymer is formed by polymerization of monomers with double
or triple bonds (unsaturated compounds). Note, in this process, there is no
elimination of small molecules like water or alcohol etc (no by-product of the
process). Addition polymers always have their empirical formulas same as
their monomers.
• Example: ethene n(CH2=CH2) to polyethene -(CH2-CH2)n-.
• Condensation polymers:
• These polymers are formed by the combination of monomers, with the
elimination of small molecules like water, alcohol etc. The monomers in these
types of condensation reactions are bi-functional or tri-functional in nature.
• A common example is the polymerization of Hexamethylenediamine and
adipic acid. to give Nylon – 66, where molecules of water are eliminated in the
process.

12. Classification Based on Molecular Forces
Intramolecular forces are the forces that hold atoms together within a molecule.
In Polymers, strong covalent bonds join atoms to each other in
individual polymer molecules.
Intermolecular forces (between the molecules) attract polymer
molecules towards each other.
Properties exhibited by solid materials like polymers depend largely on the
strength of the forces between these molecules.
Using this, Polymers can be classified into 4 types
• Elastomers:
• Elastomers are rubber-like solid polymers that are elastic in nature. Elastic
polymers mean that the polymer can be easily stretched by applying a little
force.
• The most common example of this can be seen in rubber bands (or hair bands).
Applying a little stress elongates the band.
• The weakest intermolecular forces, hence allowing the polymer to be
stretched, hold the polymer chains. But by removing that stress also results in
the rubber band taking up its original form. This happens as we introduce
crosslinks between the polymer chains, which help it in retracting to its
original position, and taking its original form.

13. • Thermoplastics:
• Thermoplastic polymers are long-chain polymers in which inter-molecules forces
(Van der Waal’s forces) hold the polymer chains together. These polymers when
heated are softened (thick fluid like) and hardened when they are allowed to cool
down, forming a hard mass. They do not contain any cross bond and can easily be
shaped by heating and using moulds.
A common example is Polystyrene or PVC (which is used in making pipes).
• Thermosetting:
• Thermosetting plastics are polymers which are semi-fluid in nature with low
molecular masses. When heated, they start cross-linking between polymer chains,
hence becoming hard and infusible. They form a three-dimensional structure on
the application of heat. This reaction is irreversible in nature.
The most common example of a thermosetting polymer is that of Bakelite, which is
used in making electrical insulation.
• Fibres:
• In the classification of polymers, these are a class of polymers, which are a thread
like in nature, and can easily be woven. They have strong inter-molecules forces
between the chains giving them less elasticity and high tensile strength. The
intermolecular forces may be hydrogen bonds or dipole-dipole interaction. Fibres
have sharp and high melting points.
A common example is that of Nylon-66, which is used in carpets and apparels

14. POLYMER SYNTHESIS
To make polymers, monomers have to interact with each other.
The structure of the monomer molecule will tell us how we should
polymerize it.
A monomer may be unsaturated; in other words it may contain a double
bond of σ (sigma) and π (pi) between a pair of electrons. The π bond
generally requires low energy to break; therefore, polymerization starts
at this site by the addition of a free radical on the monomer.
On the other hand, if a monomer does not contain a double bond but
possesses functional groups such as hydroxyl, carboxyl, or amines, they
can interact via condensation.

15. Addition Polymerization
• Free-radical polymerization is also known as chain or addition polymerization. As the
name implies, a radical generating ingredient induces an initiator triggering
polymerization.
The process of addition polymerization is consisted of following steps
• Initiation
• The initiator is an unstable molecule that is cleaved into two radical-carrying species
under the action of heat, light, chemical, or high-energy irradiation.
• Each initiating radical has the ability to attack the double bond of a monomer.
• In this way, the radical is transferred to the monomer and a monomer radical is
produced.
• This step in polymerization is called initiation.
• Propagation
• The monomer radical is also able to attack another monomer and then another
monomer, and so on and so forth.
• This step is called propagation by which a macroradical is formed

16. • Termination
Macroradicals prepared in this way can undergo another reaction with another
macroradical or with another inert compound (e.g., an impurity in the reaction)
which terminates the macroradical.
Figure shows the free-radical
polymerization of styrene, a monomer,
to polystyrene. Monomers such as
acrylic acid, acrylamide, acrylic salts
(such as sodium acrylate), and acrylic
esters (methyl acrylate) contain double
bonds and they can be polymerized via
addition reactions

17. Condensation Polymerization
• In condensation polymerization, also called step polymerization, two or
more monomers carrying different reactive functional groups interact
with each other as shown in Figure.
For example, a monomer containing a reactive hydrogen from the amine residue can
react with another monomer containing a reactive hydroxyl group (a residue of
carboxyl group) to generate a new functional group (amide) and water as a side
product

18. PHARMACEUTICAL POLYMERS
• Rosin
• Rosin is a solid form of resin obtained from pines and some other plants, a film‐forming biopolymer
and its derivatives have been extensively evaluated pharmaceutically as filmcoating and
microencapsulating materials to achieve sustained drug release. They are also used in cosmetics,
chewing gums, and dental varnishes. Rosin has been used to prepared spherical microcapsules by a
method based on phase separation or by solvent evaporation. Rosin combination with polyvinyl
pyrrolidone and dibutyl phthalate (30 % w/w) produces smooth film with improved elongation and
tensile strength.
• Chitin and Chitosan
• Chitin a naturally abundant muco polysaccharide and consist of 2‐acetamido‐2‐ deoxy‐b‐D‐glucose.
Chitin can be degraded by chitinase. Chitosan is a linear polysaccharide composed of randomly
distributed β‐(1‐4)‐linked D‐glucosamine (deacetylated unit) and N‐acetylD glucosamine (acetylated
unit). The most important property of chitosan with regards to drug delivery is its positive charge
under acidic conditions. This positive charge comes from protonation of its free amino groups. Lack
of a positive charge means chitosan is insoluble in neutral and basic environments
• Zein
• Zein an alcohol‐soluble protein contained in the endosperm tissue of Zeamais, occurs as a
by‐product of corn processing. Zein has been employed as an edible coating for foods and
pharmaceuticals for decades. Zein is an inexpensive and most effective substitute for the fast
disintegrating synthetic and semi synthetic film coatings currently used for the formulation of
substrates that allow extrusion coating

19. • Collagen
• Collagen is the most widely found protein in mammals and is the major
provider of strength to tissue. It not only has been explored for use in various
types of surgery, cosmetics and drug delivery, but in bioprosthetic implants
and tissue engineering of multiple organs.
• Starches
• It is the principal form of carbohydrate reserve in green plants and especially
present in seeds and underground organs. Starch occurs in the form of
granules (starch grains), the shape and size of which are characteristic of the
species, as is also the ratio of the content of the principal constituents,
amylose and amylopectin.
• A number of starches are recognized for pharmaceutical use. These include
maize (Zea mays), rice (Oryza sativa), wheat (Triticum aestivum), and potato
(olanum tuberosum).
• Polycaprolactone
• Polycaprolactone (PCL) is biodegradable polyester with a low melting point
of around 60°C and a glass transition temperature of about −60°C. PCL is
prepared by ring opening polymerization of ε‐caprolactone using a catalyst
such as stannous octanoate. The most common use of polycaprolactone is in
the manufacture of speciality polyurethanes. Polycaprolactones impart good
water, oil, solvent and chlorine resistance to the polyurethane produced.

20. CLASSIFICATION OF BIOMEDICAL PHARMACEUTICAL
POLYMERS
Polymers have played important roles in the preparation of biomedical pharmaceutical
products.
Their applications range widely from material packaging to fabrication of the most
sophisticated drug delivery devices.
Of the many materials used in the pharmaceutical formulations, polymers play the
most important roles.
Polymers in pharmaceutical applications are classified into three general categories
according to their common uses:
1. Polymers in conventional dosage forms
2. Polymers in controlled release dosage forms
3. Polymers for drug packaging
From the solubility point of view, pharmaceutical polymers can be classified into two
categories:
1. Water-soluble polymers
2. Water-insoluble polymers (oil soluble or organic soluble)

21. Polymers in Conventional Dosage Forms
Despite the well-known advantages of controlled release dosage forms,
conventional dosage forms are still more widely used, probably because they cost
less to manufacture. More than three-quarters of all drug formulations are made for
oral administration. Oral dosage forms such as tablets, capsules, and liquids are still
most popular.
Polymers Used in Modified Release Dosage Forms
One of the most important applications of polymers in modern pharmaceutics is the
development of new, advanced drug delivery systems, commonly known as
controlled release drug delivery systems. Controlled release formulations attempt to
alter drug absorption and subsequent drug concentration in blood by modifying the
drug release rate from the device. Polymer use in controlled release dosage
is reduced fluctuations in the plasma drug concentration, less side effects, and
increased patient compliance. Controlled release products consist of the active agent
and the polymer matrix or membranes that regulate its release.

22. Advances in controlled release technology in recent years have been possible as a
result of advances in polymer science that allow the fabrication of polymers with tailor
made specifications, charge density, such as molecular size, specific functional groups,
hydrophobicity, biocompatibility, and degradability.
Controlled release dosage forms refresh old drugs by reducing pharmaceutical
shortcomings and improving biopharmaceutical properties of the drugs. Polymers used
in controlled release dosage forms are an alternative to the development of new drugs,
which is extremely costly. The controlled release dosage forms are also important in
the delivery of newly developed protein drugs. Currently, most protein drugs are
administered by injection. Although protein drugs have delicate bioactivity, its success
in treating chronic illness
largely depends on the development of new delivery systems for the routine
administration other than injection.

23. POLYMERIZATION METHODS
Reactions may be carried out in homogeneous or heterogeneous
systems.
The former includes bulk and solution polymerizations, whereas the
latter includes any dispersed system such as suspensions, emulsions,
and their reverse phase counterparts; in other words, inverse
suspensions and inverse emulsions.
Homogeneous Polymerization
• Bulk polymerization occurs when no other materials except the
monomer and initiator are used. If the monomer is water-soluble, a
linear water-soluble polymer is theoretically prepared.
• With oil-soluble monomers, the polymer will be linear and soluble in
oil.
• Surprisingly, sometimes when an olefinic (unsaturated hydrocarbons)
water-soluble monomer is polymerized in bulk, a water-swellable
polymer is prepared. This is due to excessive exothermic heat
resulting in hydrogen abstraction from the polymer backbone, which
promotes cross-linking reactions at the defective site.

24. The cross-linked polymer obtained without using any chemical cross-
linker is called a popcorn polymer and the reaction is called “popcorn
polymerization.”
• Crospovidone, a superdisintegrant in solid dose formulations, is a
cross-linked polymer of vinyl pyrrolidone which is produced by
popcorn polymerization.

25. • Dispersion Polymerization
• Dispersion polymerization occurs in
• Suspensions,
• Emulsions,
• Inverse suspensions,
• Inverse emulsions.
• In dispersion polymerization, two incompatible phases of water and oil are
dispersed into each other. One phase is known as the minor (dispersed) phase
and the other as the major (continuous) phase.
• The active material (monomer) can be water-soluble or oil-soluble.
• To conduct polymerization in a dispersed system, the monomer (in the
dispersed phase) is dispersed into the continuous phase using a surface-active
agent.
• The surfactant is chosen on the basis of the nature of the continuous phase.
Generally, a successful dispersion polymerization requires that the surfactant be
soluble in the continuous phase. Therefore, if the continuous phase is water, the
surfactant should have more hydrophilic groups. On the other hand, if the
continuous phase is oil, a more hydrophobic (lipophilic) surfactant would be
selected.
• Generally, two basic factors control the nature of the dispersion system. These
are surfactant concentration and the surface tension of the system (nature of the
dispersed phase)

26. • The surfactant concentration determines the size of the polymer particles.
• The system will be a suspension or inverse suspension with particle sizes
around 0.2 to 0.8 mm below the critical micelle concentration.
• Above the critical micelle concentration, 10 to 100 μm particles are formed.
Nanosize particles can be made if a sufficient amount of surfactant is used.
Nanoemulsion or inverse nanoemulsion systems are rarely used in the
pharmaceutical industry because of the amount of surfactant required to
stabilize the system.
• Surfactants represent undesirable impurities that affect drug stability and
formulation acceptability.
• Water-insoluble polymers based on acrylic or methacrylic esters are prepared
via suspension or emulsion polymerization.
• Eudragit L30 D is a copolymer of methacrylic acid and ethyl acrylate which is
manufactured using an emulsion technique.
• Eudragit NE30D is also a copolymer of ethyl acrylate and methyl methacrylate
which can be manufactured in an emulsion system.
• On the other hand, water-soluble polymers based on acrylic or methacrylic
salts as well as acrylamide can be prepared using inverse suspension or
inverse emulsion systems.
• Emulsion systems that use water as a continuous phase are known as latex.

27. • COPOLYMERS AND POLYMER BLENDS
• If one polymer system cannot address the needs of a particular
application, its properties need to be modified. For this reason,
polymer systems can be physically blended or chemically reacted.
With the former, a two-phase system generally exists, whereas with
the latter a monophase system exists.
• Copolymerization refers to a polymerization reaction in which more
than one type of monomer is involved. Generally, copolymerization
includes two types of monomers.
• If one monomer is involved, the process is called polymerization and
the product is a homopolymer.
• For example, polyethylene is a homopolymer since it is made of just one type
of monomer

28. • Depending on their structure, monomers display different reactivities
during the polymerization reaction.
• If the reactivities of two monomers are similar, there will be no preference for
which monomer is added next, so the polymer that is formed is called a
random copolymer.
• When one monomer is preferentially added to another monomer, the
monomers are added to each other alternatively and the polymer product is
called an alternate copolymer.
• Sometimes, monomers preferentially add onto themselves and a block
copolymer is formed.
• This happens when one monomer has a very high reactivity toward itself.
• Once more reactive monomers have participated in the reaction, the
macroradical of the first monomer will attack the second monomer
with the lower activity, and the second monomer will then grow as a
block.
• Pluronic surfactants (EO-PO-EO terpolymers) are composed of block
units of ethylene oxide and propylene oxides attached to each other.

29. • The major difference between graft copolymer and the other
copolymer types is the nature of their building blocks.
• Other copolymer types are made of two or more monomer types,
while a monomer and a polymer are generally used to make graft
copolymers.
• For example, the physical chemical properties of carboxymethyl cellulose
(CMC) can be changed by grafting various monomers such as acrylic acid,
acrylamide, and acrylonitrile onto the cellulose backbone.
• Although not very common, a terpolymer will be obtained when three
monomers participate in the polymerization reaction.