Polymer science for pharmaceuticals

Introduction:
Polymers are macromolecules that are formed by coordination of covalent bond among the same
or different structural units. They are used in a variety of areas including drug delivery
development to general applications; current applications extend from coatings, adhesives, foams,
and packaging materials to industrial fibers and textiles, electronic devices, composites,
biomedical devices, optical devices, and novel approaches in drug delivery aspects.
Polymer Science or Macromolecular Science is a subfield of Materials Science. Polymer Science
has been the backbone for the development of new formulations for past few years and its advances
have led to development of several applications in pharmaceutical science.

Definition:
The term "polymer" derives from the ancient Greek word polus, meaning "many, much" and
meros, meaning "parts", and refers to a molecule whose structure is composed of multiple
repeating unit.
Polymers are high molecular weight compounds or macromolecules composed of many repeating
subunits called “MONOMERS”, connected by covalent bonds or chemical bonds. The reaction
involving combination of two or more monomer units to form a long chain polymer is termed as
polymerization.
Classification of Polymers
A. Based on Backbone

1. Polymers with carbon chain backbone:

Polyethylene, Polypropylene, Polystyrene, Poly (vinyl chloride), Polyacrylonitrile,
Polyacrylamide, Poly (vinyl alcohol), Poly (methyl methacrylate), Poly vinylpyrrolidone
2. Polymers with heterochain backbone:
Poly (ethylene oxide), Poly (propylene oxide), cellulose (Poly-glucopse,ß-→1.4), Amyloose
(Poly-glucoside,a-1,4) (Component of starch), Pectinic acid (Polygalacytouronoside), Polyehylene
glycolterepthalate, Polydimethylsiloxane etc.

B. Based on Occurrence

1. Natural polymers: Natural polymers are derived from natural sources and can be
polysaccharides and proteins in chemical nature.
Protein-based polymers: Collagen, albumin, gelatin etc.
Polysaccharides: Agarose, alginate, carrageenan, hyaluronic acid, dextran, chitosan, cyclodextrins
2. Synthetic polymers: Synthetic polymers are of artificial origin which consists of fibers
like Teflon and Dacron, Synthetic Rubbers, Plastics and PVC.

It has the following subtypes

I. Biodegradable Polymers: Biodegradable polymers are defined as polymers

comprised of monomers linked to one another through functional groups and have
unstable links in the backbone. They are broken down into biologically acceptable
molecules that are metabolized and removed from the body via normal metabolic
pathways.

a) Natural Bio-degradable polymer: These polymer are very common in nature. The use of these
polymers is limited because of their high costs and questionable purity. Examples-Albumin,
Collagen, Gelatin, Starch etc.

b) Synthetic Bio-degradable polymers: These types of polymers are preferred rather than natural
bio-degradable polymers due to their inertness and easy and cheap formulation.

Synthetic bio-degradable polymers have following advantages over natural ones:

Localized delivery of drug. Sustain delivery of drug. Stabilization of drug.Reduced side effects
etc. Examples-Poly lactide homopolymer, Polyester etc.

C) Semi-Synthetic Polymers: These types of polymers are derived from naturally occurring
polymers by means of chemical modifications. E.g. Vulcanized rubber, Gun cotton, Cellulose
diacetate, HPMC etc.,
d) Polyesters: Poly (lactic acid), poly(glycolic acid), poly(e-caprolactone), poly(ß-malic acid),
poly(dioxanones) poly(hydroxybutyrate),
e). Polyanhydrides: Poly (sebacic acid), poly(adipic acid),poly(terphthalic acid) and various
copolymers
g). Phosphorous-based polymers: Polyphosphates, polyphosphonates, polyphosphazenes
h) Others: polyacetals
Poly(cyano acrylates), polyurethanes, polyortho esters, polydihydropyrans,

II. Non-Biodegradable Polymer

It includes the followings

a. Cellulose derivatives: Carboxymethyl cellulose, ethyl cellulose, cellulose acetate, cellulose
acetate propionate, hydroxypropyl methyl cellulose
b.Silicones: Polydimethylsiloxane, colloidal silica
c.Acrylicpolymers:Polymethacrylates, poly(methylmethacrylate), polyhydro (ethylmethacrylate)

d. Others: Polyvinyl pyrrolidone, ethyl vinyl acetate, poloxamers, poloxamines

C. Based Upon Molecular Forces

Thermoplastic Polymer: Some polymer are soften on heating and can be converted into
any shape that they can retain on cooling. Such polymer that soften on heating and stiffen on
cooling are termed as 'thermoplastic' polymers. Ex. Polyethylene, PVC, nylon, sealing wax.

Thermosetting Polymer : Polymer that become an infusible and insoluble mass on heating
are called 'thermosetting' polymers. Thermosetting polymers are cross-linked polymers, which are
formed upon combined application of a cross-linker and heat or combined application of heat and
reaction of internal functional groups.

Plastics made of these polymers cannot be stretched, are rigid and have a high melting point. Ex.
Polyurethanes, Bakelite, phenol-formaldehyde ,Melamine resin ,Epoxy resin , Polyimides

Elastomers: When plastics are vulcanised into rubbery products exhibiting good strength
and elongation, polymers are known as 'elastomers'. E.g. silicone rubber, natural rubber, synthetic
rubber, etc.

Fibres: The polymers which are filament like materials, having their length at least 100
times to their diameter, are said to be 'fibres'. E.g. Nylon, terylene.

D. Based on Composition:
1. Homopolymer: Homopolymers- consist of chains with identical bonding linkages to each monomer unit.
This usually implies that the polymer is made from all identical monomer molecules. These may be
represented as : -[A-A-A-A-A-A]e.g. Polyethylene, polystyrene.
2. Copolymer: A polymer of two or more different monomers. The synthetic rubber used to make tire treads and shoe
soles, for example, is a copolymer made of the monomers butadiene and styrene These may be represented as :-[A-B-
A-B-A-B]e.g. Silicone, Ethyl cellulose.

Physical, chemical and mechanical properties of polymers:

Polymer properties are broadly divided into several classes based on the scale at which the property
is defined as well as upon its physical basis. These are as follows:

1. Monomers and repeat units 4. Mechanical properties

2. Microstructure a) Tensile strength
a) Polymer architecture b) Young's modulus of elasticity
b) Chain length
c) Monomer arrangement in copolymers 5. Transport properties
d) Tacticity 6. Phase behavior
3. Polymer morphology a). Melting point
a) Crystallinity b) Glass transition temperature
b) Chain conformation c). Mixing behavior
d) Inclusion of plasticizers
7. Chemical properties
8. Optical properties

a) Monomers and repeated units

The first and most important attribute of the repeat units (monomer residues, also known as "mers")
comprising a polymer is its identity. Polymers that contain only a single type of repeat unit are
known as homopolymers, while polymers containing a mixture of repeat units are known as
copolymers.

For example, polynucleotides such as DNA are composed of a variety of nucleotide subunits.A
polymer molecule containing ionizable subunits is known as a polyelectrolyte or ionomer.

2. Microstructure

The microstructure of a polymer (sometimes called configuration) relates to the physical

arrangement of monomer residues along the backbone of the chain. These are the elements of
polymer structure that require the breaking of a covalent bond in order to change.
a) Polymer architecture

An important microstructural feature of a polymer is its architecture and shape, which relates to
the way in which the branch points lead to a deviation from a simple linear chain. A polymer's
architecture affects many of its physical properties including, solution viscosity, solubility in
various solvents, glass transition temperature and the size of individual polymer coils in solution.

b) Chain length

The physical properties of a polymer are strongly dependent on the size or length of the polymer
chain. For example, as chain length is increased, melting and boiling temperatures increase
quickly. Increasing chain length furthermore tends to decrease chain mobility, increase strength
and toughness, and increase the glass transition temperature (TG).

c) Monomer arrangement in copolymers

Monomers within a copolymer may be organized along the backbone in a variety of ways.

Alternating copolymers Periodic copolymers Statistical copolymers Block Graft or grafted

copolymers

d) Tacticity

Tacticity describes the relative stereochemistry of chiral centers in neighboring structural units
within a macromolecule. There are three types: isotactic (all substituents on the same side), atactic
(random placement of substituents), and syndiotactic (alternating placement of substituents).

3. Polymer morphology

Polymer morphology generally describes the arrangement and microscale ordering of polymer
chains in space.

a) Crystallinity

Synthetic polymers may consist of both crystalline and amorphous regions; the degree of
crystallinity may be expressed in terms of a weight fraction or volume fraction of crystalline
material.

b) Chain conformation

The space occupied by a polymer molecule is generally expressed in terms of radius of gyration,
which is an average distance from the center of mass of the chain to the chain itself.

4. Mechanical properties

These are the properties that dictate how the polymer actually behaves on a macroscopic scale.
a) Tensile strength

The tensile strength is very important in applications that rely upon a polymer's physical strength
or durability.

b) Young's modulus of elasticity

Young's Modulus quantifies the elasticity of the polymer. It is defined, for small strains, as the
ratio of rate of change of stress to strain. Like tensile strength, this is highly relevant in polymer
applications involving the physical properties of polymers, such as rubber bands.

5. Transport properties

Transport properties are very important in many applications of polymers for films and
membranes.

6. Phase behavior

a) Melting point

The term melting point, when applied to polymers, suggests not a solid-liquid phase transition but
a transition from a crystalline or semi-crystalline phase to a solid amorphous phase.

b). Glass transition temperature

A parameter of particular interest in synthetic polymer manufacturing is the glass transition

temperature (T.), at which amorphous polymers undergo a transition from a rubbery, viscous
liquid, to a brittle, glassy amorphous solid on cooling. The glass transition temperature may be
engineered by altering the degree of branching or crosslinking in the polymer or by the addition of
plasticizer.

c) Mixing behavior

In general, polymeric mixtures are far less miscible than mixtures of small molecule materials. In
dilute solution, the properties of the polymer are characterized by the interaction between the
solvent and the polymer.
d). Inclusion of plasticizers
Inclusion of plasticizers tends to lower T, and increase polymer flexibility.
7. Chemical properties

The attractive forces between polymer chains play a large part in determining polymer's properties.
Different side groups on the polymer can lend to: Ionic bonding Hydrogen bonding Polymers
containing amide or carbonyl groups can form hydrogen bonds between adjacent chains.
Polyesters have dipole –dipole bonding between the oxygen atoms in C=O groups and the
hydrogen ato.ms in C-H groups. Dipole bonding is not as strong as hydrogen bonding

8. Optical properties
Polymers such as Poly(methyl methacrylate) :PMMA and HEMA: MMA are used as matrices in
the gain medium of solid-state dye lasers that are also known as polymer lasers.
9. Mechanical properties
Depending on their structure, molecular weight, and intermolecular forces, polymers resist
differently when they are stressed. For elastic materials the stress and strain correlation is linear
upto the failure point For fibers and height cross linked polymers the slope of the stress and strain
line is steeper. Energy is needed to break the polymer. The area under the stress/strain measures
it. The larger the area, is the tougher the polymer.

Number Average Molecular Masses:

If N1, N2, N3…. are the number of macromolecular with molecular masses. M1, M2, M3….. ,
respectively then the number average molecular masses of the polymer is given by
The number average molecular mass
is determined by colligative properties such as Osmotic Pressure.

Weight Average Molecular Mass:

If m1, m2, m3…. Are the masses of a macromolecule with molecular masses M1, M2, M3…,
respectively, Then weight average molecular mass of the polymer is given by

Polydispersive index: It is the ratio of weight average molecular mass and number
average molecular mass of Polymers.

Characteristics of an ideal polymer

An ideal polymer should have the following properties

1. It should be versatile and possess a wide range of mechanical, physical, chemical

properties.

2. It should be non-toxic.

3. It should have good mechanical strength.

4. It should be easily administered.

5. It should be inexpensive and easy to fabricate the dosage form.

6. It should be inert to host tissue.

7. It should be compatible with environment.

Application of Polymers in Pharmaceuticals

1. Artificial Heart.

2. Bones, Joints, and Teeth.

3. Contact Lenses and Intraocular Lenses.

4. Artificial Kidney and Hemodialysis Materials.

5. Oxygen-Transport Membranes.

6. Surgical structure

7. Water-Soluble Synthetic Polymers

Poly (acrylic acid): Immobilization of cationic drugs, base for Carbopol polymers

Poly (ethylene oxide): Coagulant, flocculent, swelling agent

Poly (ethylene glycol): plasticizer, base for suppositories

Poly (vinyl pyrrolidone): Used to make betadine (iodine complex of PVP) with

less toxicity than iodine, plasma replacement, and tablet granulation

Poly (vinyl alcohol): Water-soluble packaging, tablet binder, tablet coating

Polyacrylamide: Gel electrophoresis to separate proteins based on their

molecular weights, coagulant,absorbent

Poly (isopropyl acrylamide) and poly (cyclopropyl methacrylamide)

8. Thermogelling acrylamide derivatives, its balance of hydrogen bonding, and

hydrophobic association changes with temperature

Cellulose-Based Polymers

Ethyl cellulose: Insoluble but dispersible in water, aqueous coating system for

9. Sustained release applications

Carboxymethyl cellulose: Superdisintegrant, emulsion stabilizer

Hydroxyethyl and hydroxypropyl celluloses: Soluble in water and in alcohol, tablet coating.

Hydroxypropyl methyl cellulose: Binder for tablet matrix and tablet coating, gelatin alternative as
capsule material

Cellulose acetate phthalate: Enteric coating

10. Water-Insoluble Biodegradable Polymers (Lactide-co-glycolide) polymers:

Microparticle–nanoparticle for protein delivery

11. Starch-Based Polymers

Starch: Glidant, a diluent in tablets and capsules, a disintegrant in tablets and capsules, a tablet
binder

Sodium starch glycolate: Superdisintegrant for tablets and capsules in oral delivery

12. Hydrocolloids
Alginic acid: Oral and topical pharmaceutical products; thickening and suspending agent in a
variety of pastes, creams, and gels, as well as a stabilizing agent for oil-in-water emulsions; binder
and disintegrant.

Carrageenan: Modified release, viscosifier

Chitosan: Cosmetics and controlled drug delivery applications, mucoadhesive dosage forms, rapid
release dosage forms

Hyaluronic acid: Reduction of scar tissue, cosmetics

Pectinic acid: Drug delivery

PLASTICIZER
A plasticizer or softener is a substance incorporated in a material (usually a plastic) to increase the
flexibility, elongation, workability, dispensability.

A Plasticizer is a distinct polymer additive, that increase the plasticity or viscosity of a material.

Ideal properties of plasticizers:

1. It should be flexible resilient (fsfotot lelastic) and easier to handle.

2. It should be non-volatile with high boiling point.

3. It should not come out from materials to which it is added.

4. Plasticizers used for internal purpose should be non-toxic.

5. It should lower the tensile strength and softening temperature, of the polymeric materials
to which it is added.

6. It should reduce the brittleness, improve flow, flexibility, and increase toughness, shear
strength, and impart resistance to the polymeric film coating.

7. It should lower the glass transition temperature of the polymeric film coating.

8. It should reduce the viscosity of materials to which it is added.

9. It should impart permanent properties such as liability, shock resistance, hand drop.
 10. The main role of the plasticizer is to improve mechanical properties of the polymers by
increasing flexibility, decreasing tensile strength and lowering the second order transition
temperature.

Why do we need plasticizers?

Almost all the film forming agents or polymers are brittle in nature due to their complex structure.
Most commonly used polymers are the cellulose derivatives or cellulose related compounds like
HPMC, MC, EC, Nitrocellulose, HPMCP etc. These polymers are widely used as film forming
materials as they:

► Produce transparent films

► Produce intact films

► They have lower values for water vapor permeability rate.

► They have lower values for oxygen transmission rates.

They can be structurally modified to achieve sustained release, like HPMC can be converted to
HPMCP for enteric coating. But due to the presence of multiple polymeric strands within a single
molecule of polymer makes them brittle. When such a material is applied as a film coat on to tablet
a smooth film will not be obtained. This condition necessitates the addition of plasticizers to the
coating/Film forming dispersions. The addition of plasticizers to polymeric material causes them
to diffuse within the polymers and cause polymer deformation and coalescence into homogeneous
films.

The effectiveness of plasticizers on polymeric dispersion depends upon polymer compatibility and
the permanence of plasticizer during the course of shelf life, or when it comes in contact with
physiological fluids.

Effect of Plasticizers

• Easy melt

• Improve flexibility

• Increase Softness and Flexibility

• Improve Process ability

• Alters Softening point, Tensile Strength, Elongation at break & Impact.

Mechanism of action
• The mechanism of action of plasticizers is defined as to interpose between every individual strand
of polymer and thereby causing breakdown of polymer -polymer interactions.

• The tertiary structure of the polymer is modified into more porous, flexible and with less cohesive
structure.

• Plasticizers soften and swell the polymer (latex spheres) which aids in overcoming their
resistance to deformation.

• As a result, the plasticized polymer would deform at a lower tensile force as compared to without
plasticizer. This enhances the polymer -plasticizer interaction.

• This effect in turn enhances the film elongation effect.

• This interaction to a greater extend depends upon the glass transition temperature of polymers.
Glass transition temperature, Tg is the temperature at which hard glassy polymer is converted into
a rubbery material.

• All polymers have higher glass transition temperatures and addition of plasticizers reduces the
glass transition temperature.

• As plasticizers usually possess relatively long alkyl chains, they have the effect of screening the
polymer chains from each other, thereby preventing them from re-forming the chain-chain
interactions which give the unplasticized polymer its rigidity.

Plasticization
Plasticization, in general, refers to a change in the thermal and mechanical properties of a given
polymer which involves:

(a) Lowering of rigidity at room temperature;

(b) Lowering temperature at which substantial deformation can be effected with not to
large force.

(c) Incensement of the elongation to break at room temperature;

(d) Incensement of the toughness (impact strength) down to the lowest temperature of
serviceability.

These effects can be achieved:

(1) By compounding the given polymer with a low molecular weight compound or with another
polymer and
(2) By introducing into the original polymer a comonomer (one of the constituents of a copolymer)
which reduces crystallizability and increases chain flexiblity

Plasticization theories

There are mainly 3 theories regarding plasticization. These are as follows. Lubricity theory:

• According to Lubricity Theory the Plasticizer acts as a lubricant, reducing intermolecular

friction between polymer molecules responsible for rigidity of the polymer.
• This theory assumes the rigidity of the resin (pure polymer) arises from "intermolecular
friction."
• A "dry" polymer, a resin without plasticizer, is rigid because friction exists between its
chains, binding them into a network.
• When the polymer is heated in order to be plasticized, the binding is weakened and the
smaller plasticizer molecules are able to slip in between the chains.
• When the polymer cools, the plasticizer molecules act as a lubricant between the chains,
allowing them to "slip."

Gel theory:

According to Gel Theory the Polymers are formed by an internal three-dimensional network.

• The plasticizer molecules break up the polymer-polymer interaction by getting in between

the chains and "obscuring" these interaction sites from the polymer molecules.
• Resin-resin interactions occur at "centers of attachment." Plasticizer molecules break these
interactions and masks the centers from each other, preventing re-formation. This theory is
not sufficient to describe interaction- should be combined with Lubricity Theory.

The free volume theory:

• According to the Free Volume Theory the Plasticizer lowers the glass transition
temperature (Tg) of the polymer.
• The free volume of a polymer can be described as the "empty internal space" available for
the movement of the polymer chains. The free volume of a polymer greatly increases when
it reaches the glass transition temperature.
• At the glass transition temperature, the molecular motion begins to occur, which
corresponds to an increase in the free volume of the polymer.
• Plasticizer is meant to decrease the glass transition temperature, imparting increased
flexibility to polymer at room temperature.
• These plasticizer molecules are having low glass transition temperature than the polymer,
so that Tg of the resulting mixture will be lower.
Mechanistic Theory:

Plasticizer molecules are not bound permanently to the polymer molecules form.

PLASTICIZERS IN FILM COATING

There are more than 300 different types of plasticizers available. The most commonly used
plasticizers are ester like phthalates, adipates and trimellitates.

The commonly used plasticizers can be categorized into three groups:

1. Polyols:

(a) Glycerol (glycerin);

(b) Propylene glycol;

(c) Polyethylene glycols PEG (generally the 200-6000 grades).

2. Organic esters:

(a) Phthalate esters (diethyl, dibutyl);

(b) Dibutyl sebacete;

(c) Citrate esters (triethyl, acetyl triethyl, acetyl tributyl);

(d) Triacetin.

3. Oils/ glycerides:

(a) Castor oil;

(b) Acetylated monoglycerides;

(c) Fractionated coconut oil

4. Newer Plasticizers - DBS (Dibutyl Sebacate).

Plasticized Polymers
A plasticizer is added to a polymer formulation to enhance its flexibility and to help its
processing. It facilitates relative movement of polymer chains against each other. The addition of
a plasticizer to a polymer results in a reduction in the glass transition temperature of the mixture.
Since plasticizers increase molecular motion, drug molecules can diffuse through the plasticized
polymer matrix at a higher rate depending on the plasticizer concentration.

Example: Plasticized Polymers

• Fluoxetine (Prozac Weekly) (fluoxetine hydrochloride) capsules contain hydroxypropyl

methylcellulose and hydroxypropyl cellulose acetate succinate plasticized with sodium
lauryl sulfate and triethyl citrate.
• Omeprazole magnesium (Prilosec), a delayed release oral suspension, contains
hydroxypropyl cellulose, hydroxypropyl methylcellulose, and methacrylic acid
copolymer plasticized with glyceryl monostearate, triethyl citrate, and polysorbate.
• Triacetin can be found in ranitidine HCI (Zantac) 150-tablet formulations, which contains
hydroxypropyl methylcellulose as its polymer matrix.
• Dibutyl sebacate is found in methylphenidate HCI (Metadate) CDwhich contains
polymers such as povidone, hydroxypropyl methylcellulose, and ethyl cellulose.

Elastomers
An elastomer is a polymer with viscoelasticity (having both viscosity and elasticity). The term,
which is derived from elastic polymer, is often used interchangeably with the term rubber, although
the latter is preferred when referring to vulcanisates.

Elastomeric materials are those materials that are made of polymers that are joined by chemical
bonds, acquiring a final slightly cross-linked structure. The main characteristic of elastomer
materials is the high elongation and flexibility or elasticity of these materials, against its breaking
or cracking.
Depending on the distribution and degree of the chemical bonds of the polymers, elastomeric
materials can have properties or characteristics similar to thermosets or thermoplastics, so
elastomeric materials can be classified into:

1. Thermoset Elastomers - are those elastomer materials which do not melt when heated.

2. Thermoplastic Elastomers - are those elastomers which melt when heated.

Properties of elastomer materials:

1. Do not melt (before melting they pass into a gaseous state.

2. Swell in the presence of certain solvents.

3. Generally insoluble.

4. Flexible and elastic.

5. Lower creep resistance than the thermoplastic materials.

Examples and applications of elastomer plastic materials:

1. Natural rubber - It is used in pharmaceutical vial closures.

2. Polyurethanes - Generally they are used in these medical applications:

a) Diaphragms c) Surgical apparatus

b) Membranes d) Mechanical supports

3. Neoprene – It is used primarily in the manufacture of medical gloves.

4. Silicone - Silicones are used in a wide range of materials and areas due their excellent thermal
and chemical resistance. Silicones are used today in many life-saving medical devices like
pacemakers or hydrocephalic shunts. They are also used as excipients in topical formulations or
adhesives to affix transdermal drug delivery systems. They also have found use as active
pharmaceutical ingredients in products such as antacid and anti-flatulent formulations.

5. Medical Thermoplastic elastomers (TPE) products include drip chambers, seals, medical,
artificial skin to many of the artificial human body parts, drug encapsulation purposes etc.

References:
• https://chemed.chem.purdue.edu/genchem/topicreview/bp/1polymer/property.html
• http://www.ijpacr.com/files/22-10-16/06.pdf
• Researchgate
• https://www.slideshare.net/saikathossain4/polymer-science-102880475
• Wikipidea