Polymer classification biodegradable polymers and pharmaceutical industry

1. Biodegradable polymers
Represented by: Ph. Mohammed Ahmed Sadek Ibrahim
Pharmaceutics department

2. Outlines
 Introduction to polymers
 Classification of polymers
 Biodegradable polymers definition& classification
 Characteristics of Biodegradable polymers
 Applications of Biodegradable polymers

3. Introduction to polymers
Polymer: The word ‘polymer’ is coined from two Greek words poly
means many and mer means unit or part. The term polymer is defined
as very large molecules having high molecular mass (103-107u).
These are also referred to as macromolecules, which are formed by
joining of repeating structural units on a large scale. The repeating
structural units are derived from some simple and reactive molecules
known as monomers and are linked to each other by covalent bonds.
This process of formation of polymers from respective monomers is
called polymerization.
Polymers include:
 proteins, such as hair, nails, tortoise shell
 cellulose in paper and trees
 DNA
 silly putty
 rubber
Monomer: The small molecule or repeating unit or the building block
in the structure of polymer is called monomer.
To be a monomer, the substance unit should have a functionality of at
least two; some compounds have two functionality other have double
or triple bonds in the molecule.
The word monomer comes from mono- (one) and -mer (part).
Monomers are small molecules which may be joined together in a
repeating fashion to form more complex molecules called polymers.
Monomers form polymers by forming chemical bonds or binding
supramolecularly through a process called polymerization. Sometimes
polymers are made from bound groups of monomer subunits (up to a
few dozen monomers) called oligomers. A related term is "monomeric
protein", which is a protein which bonds to make a multi protein
complex. Monomers are not just building blocks of polymers, but are
important molecules in their own right, which do not necessarily form
polymers unless the conditions are right.

4. Examples of Monomers
Examples of monomers include vinyl chloride (polymerizes into
polyvinyl chloride or PVC), glucose (polymerizes into starch, cellulose,
laminarin, and glucans), and amino acids (which polymerize into
peptides, polypeptides, and proteins).
Glucose the most abundant natural monomer, which polymerizes by
forming glycosidic bonds.
Polymerization: it is chemical reaction in which two or more than two
molecules of one or more than one substance combine together to form
a molecule of high molecular weight.
Degree of Polymerization: Number of monomer or repeating unit (n)
in the polymer chain is called degree of polymerization (DP)
Degree of polymerization (DP) is used to calculate the average
molecular weight of polymer.
Average molecular weight of polymer= DP X Weight of repeating
unit. For examples of two different types of polymerization reactions.
The Structure of Polymers
Many common classes of polymers are composed of hydrocarbons,
compounds of carbon and hydrogen. These polymers are specifically
made of carbon atoms bonded together, one to the next, into long
chains that are called the backbone of the polymer. Because of the
nature of carbon, one or more other atoms can be attached to each
carbon atom in the backbone. There are polymers that contain only
carbon and hydrogen atoms. Polyethylene, polypropylene,
polybutylene, polystyrene and polymethyl pentene are examples of
these. Polyvinyl chloride (PVC) has chlorine attached to the all-carbon
backbone. Teflon has fluorine attached to the all-carbon backbone.

5. Other common manufactured polymers have backbones that include
elements other than carbon. Nylons contain nitrogen atoms in the
repeat unit backbone. Polyesters and polycarbonates contain oxygen in
the backbone. There are also some polymers that, instead of having a
carbon backbone, have a silicon or phosphorous backbone. These are
considered inorganic polymers. One of the more famous silicon-based
polymers is Silly Putty.
Characteristics of Polymers
The majority of manufactured polymers are thermoplastic, meaning
that once the polymer is formed it can be heated and reformed over and
over again. This property allows for easy processing and facilitates
recycling. The other group, the thermosets, cannot be reheated. Once
these polymers are formed, reheating will cause the material to
ultimately degrade, but not melt.
Every polymer has very distinct characteristics, but most polymers
have the following general attributes.
Polymers can be very resistant to chemicals. Consider all the cleaning
fluids in your home that are packaged in plastic. Reading the warning
labels that describe what happens when the chemical comes in contact
with skin or eyes or is ingested will emphasize the need for chemical
resistance in the plastic packaging. While solvents easily dissolve some
plastics, other plastics provide safe, non-breakable packages for
aggressive solvents.
Polymers can be both thermal and electrical insulators. A walk through
your house will reinforce this concept, as you consider all the
appliances, cords, electrical outlets and wiring that are made or covered
with polymeric materials. Thermal resistance is evident in the kitchen
with pot and pan handles made of polymers, the coffee pot handles, the

6. foam core of refrigerators and freezers, insulated cups, coolers, and
microwave cookware. The thermal underwear that many skiers wear is
made of polypropylene and the fiberfill in winter jackets is acrylic and
polyester.
Generally, polymers are very light in weight with significant degrees of
strength. Consider the range of applications, from toys to the frame
structure of space stations, or from delicate nylon fiber in pantyhose to
Kevlar, which is used in bulletproof vests. Some polymers float in
water while others sink. But, compared to the density of stone,
concrete, steel, copper, or aluminum, all plastics are lightweight
materials.
Polymers can be processed in various ways. Extrusion produces thin
fibers or heavy pipes or films or food bottles. Injection molding can
produce very intricate parts or large car body panels. Plastics can be
molded into drums or be mixed with solvents to become adhesives or
paints. Elastomers and some plastics stretch and are very flexible.
Some plastics are stretched in processing to hold their shape, such as
soft drink bottles. Other polymers can be foamed like polystyrene
(Styrofoam™), polyurethane and polyethylene.
Polymers are materials with a seemingly limitless range of
characteristics and colors. Polymers have many inherent properties that
can be further enhanced by a wide range of additives to broaden their
uses and applications. Polymers can be made to mimic cotton, silk, and
wool fibers; porcelain and marble; and aluminum and zinc. Polymers
can also make possible products that do not readily come from the
natural world, such as clear sheets and flexible films.
Polymers are usually made of petroleum, but not always. Many
polymers are made of repeat units derived from natural gas or coal or

7. crude oil. But building block repeat units can sometimes be made from
renewable materials such as polylactic acid from corn or cellulosics
from cotton linters. Some plastics have always been made from
renewable materials such as cellulose acetate used for screwdriver
handles and gift ribbon. When the building blocks can be made more
economically from renewable materials than from fossil fuels, either
old plastics find new raw materials or new plastics are introduced.
Polymers can be used to make items that have no alternatives from
other materials. Polymers can be made into clear, waterproof films.
PVC is used to make medical tubing and blood bags that extend the
shelf life of blood and blood products. PVC safely delivers flammable
oxygen in non-burning flexible tubing. And anti-thrombogenic
material, such as heparin, can be incorporated into flexible PVC
catheters for open heart surgery, dialysis, and blood collection. Many
medical devices rely on polymers to permit effective functioning.
CHARACTERISTICS OF IDEAL POLYMER
 Inert and compatible with the environment.
 Non-toxic.
 Easily administered.
 Easy and inexpensive to fabricate.
 Have good mechanical strength.
PHYSICAL, THERMAL, AND MECHANICALPROPERTIES
OF POLYMERS
1. PHYSICAL PROPERTIES
 Degree of Polymerization and Molecular Weight(DP)-n : the
number of repeating units in the polymer chain
 Molecular Weight Averages

8. The physical properties (such as transition temperature, viscosity, etc.)
and mechanical properties (such as strength, stiffness, and toughness)
depend on the molecular weight of polymer. The lower the molecular
weight, lower the transition temperature, viscosity, and the mechanical
properties. Due to increased entanglement of chains with increased
molecular weight, the polymer gets higher viscosity in molten state,
which makes the processing of polymer difficult.
 Polymer Crystallinity: Crystalline and Amorphous Polymers
The polymeric chains being very large are found in the polymer in two
forms as follows:
Lamellar crystalline form in which the chains fold and make lamellar
structure
Arranged in the regular manner and amorphous form in which the
chains are in the irregular manner.
The lamellae are embedded in the amorphous part and can
communicate with other lamellae via tie molecules
Polymer may be amorphous or semi-crystalline in nature.
2. THERMAL PROPERTIES OF POLYMERS
In the amorphous region of the polymer, at lower temperature, the
molecules of the polymer are in, say, frozen state, where the molecules
can vibrate slightly but are not able to move significantly. This state is
referred as the glassy state. In this state, the polymer is brittle, hard and
rigid analogous to glass. Hence the name glassy state.
When the polymer is heated, the polymer chains are able to wiggle
around each other, and the polymer becomes soft and flexible similar to
rubber.
This state is called the rubbery state. The temperature at which the
glassy state makes a transition to rubbery state is called the glass
transition temperature
Tg. The glass transition occurs only in the amorphous region, and the
crystalline region remains unaffected during the glass transition in the
semi-crystalline polymer.

9. Factors Affecting the Glass Transition Temperature.
 Intermolecular Forces. Strong intermolecular forces cause higher Tg.
 Chain Stiffness. The presence of the stiffening groups (such as amide,
sulfone, carbonyl, p-phenylene etc.) in the polymer chain reduces the
flexibility of the chain, leading to higher glass transition temperature.
 Cross-Linking. The cross-links between chains restrict rotational
motion and raise the glass transition temperature. Hence, higher cross-
linked molecule will show higher Tg than that with lower cross-linked
molecule.
 Pendant groups. The presence of pendent group can change the glass
transition temperature.
 Plasticizers. Plasticizers are low molecular weight and non-volatile
materials added to polymers to increase their chain flexibility. They
reduce the intermolecular cohesive forces between the polymer chains,
which in turn decrease Tg.
 Molecular Weight. The glass transition temperature is also affected by
the molecular weight of the. Tg is increased with the molecular weight.
The molecular weight is related to the glass transition temperature.
Classification of Polymers

10. BIODEGRADABLE POLYMERS
A “biodegradable” product has the ability to break down, safely,
reliably, and relatively quickly, by biological means, into raw materials
of nature and disappear into nature.
In recent years, there has been a marked increase in interest in
biodegradable materials for use in packaging, agriculture, medicine,
and other areas.
In particular, biodegradable polymer materials (known as
biocomposites) are of interest. As a result, many researchers are
investing time into modifying traditional materials to make them more
userfriendly, and into designing novel polymer composites out of
naturally occurring materials.
A number of biological materials may be incorporated into
biodegradable polymer materials, with the most common being starch
and fiber extracted from various types of plants.
The belief is that biodegradable polymer materials will reduce the need
for synthetic polymer production (thus reducing pollution) at a low
cost, thereby producing a positive effect both environmentally and
economically.
This paper is intended to provide a brief outline of work that is under
way in the area of biodegradable polymer research and development,
the scientific theory behind these materials, areas in which this research
is being applied.
Biodegradable polymers are defined as polymers comprised of
monomers linked to one another through functional groups and have
unstable links in the backbone.
They slowly disappear from the site of administration in response to a
chemical reaction such as hydrolysis.
Material progressively releasing dissolved or dispersed drug, with
ability of functioning for a temporary period and subsequently degrade
in the biological fluids under a controlled mechanism, in to product
easily eliminated in body metabolism pathway.

11. Polymer Degradation
Polymer degradation is a change in the properties – tensile strength,
colour, shape, etc of a polymer or polymer based product under the
influence of one or more environmental factors such as heat, light or
chemicals.
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 bioerosion of polymers is basically of two types:-
1) Bulk erosion
2) Surface erosion
Mechanismof Biodegradable Polymers

12. Types of Hydrolysis (Bioerosion)
1) Bulk erosion
 Degradation takes place throughout the whole of the sample.
 Ingress of water is faster than the rate of degradation
Eg : Polylactic acid (PLA)
Polyglycolic acid (PGA)
2) Surface erosion
 Sample is eroded from the surface.
 Mass loss is faster than the ingress of water into the bulk
Eg:Polyanhydrides , polyorthoesters
Enzymatic Degradation
Mechanism I
Cleavage of Crosslinks

13. Mechanism II
Transformation of Side Chains
Mechanism III
Cleavage of Backbone
FACTORS AFFECTING BIODEGRADATION OF POLYMERS
 Morphological factors
Shape & size
Variation of diffusion coefficient and mechanical stresses
 Chemical factors
Chemical structure & composition
Presence of ionic group and configuration structure
Molecular weight and presence of low molecular weight compounds
 Physical factors
Processing condition
Sterilization process

14. Classification of biodegradable polymers
Classification of biodegradable polymers based on the source
1) Synthetic biodegradable polymers:
eg: Aliphatic poly(esters)
Polyanhydrides
Polyphosphazenes
polyaminoacids
Poly orthoesters etc.,
2) Natural biodegradable polymers:
eg: Albumin
Collagen
Dextran
Gelatin
Pectin, starch etc.,
3) Copolymers or blends of non-degradable polymers with type 1 or 2
polymers

15. Synthetic biodegradable polymers
1) Aliphatic poly(esters)
These are prepared by ring opening and polymerization of cyclic ester.
Aliphatic polyesters include:
a) POLY (GLYCOLIC ACID)
Polyglycolide or Polyglycolic acid (PGA) is a biodegradable,
thermoplastic polymer and the simplest linear, aliphatic polyester.
It is a tough fiber-forming polymer.
Due to its hydrolytic instability its use has been limited.
It has a glass transition elevated degree of temperature between 35-40C
crystallinity around 45.
Its melting point is in the range 55%, thus resulting in of 225-230 C.
insolubility in water.
polyglycolide is degraded by hydrolysis, and broken down by certain
enzymes.
Applications
Used to deliver drugs in the form of microspheres, implants etc.,
Examples of drugs delivered include steroid hormones, antibiotics,
anti-cancer agents etc.,
Used to make biodegradable drug matrices and sutures for
Cataract surgery and for repairing inguinal hernias.
b) POLYLACTIC ACID
Polylactic acid or polylactide (PLA) is a thermoplastic aliphatic
polyester derived from renewable resources, such as corn starch,
tapioca products (roots, chips or starch) or sugarcane.
It can biodegrade under certain conditions, such as the presence of
oxygen, and is difficult to recycle.
Highly crystalline, high melting point, low solubility.
Bacterial fermentation is used to produce lactic acid from corn starch or
cane sugar.
Applications
PLA is used in the preparation of sutures or orthopaedic devices.

16. The resistance of PLA to attack from bacteria and fungi is an advantage
for food packaging applications
The biodegradability of polymers based on lactic acid (LA) and its
copolymers with ethylene glycol (EG) opens up new avenues for:
• Encapsulation & Drug Delivery
• Gene Therapy
• Drug Targeting
• Dental & Medical Devices
• Sutures
• Tissue Engineering
• Micellar Anti-cancer Carriers
• Orthopedic Fixation Devices
• Formulation of Artificial Blood Systems
• Determination of Cellular Pathway Mechanisms
c) POLYCAPROLACTONE
Polycaprolactone (PCL) is biodegradable polyester.
It has a low melting point of around 60 C.
It has a glass transition temperature of about −60 C.
Slower degradation rate than PLA.
It remains active as long as a year for drug delivery.
Applications:
A drug delivery application of PCL includes:
- Cyclosporin in the form of nanoparticles
- Ciprofloxacin in the form of dental implants
2) Poly anhydrides
Highly reactive and hydrolytically unstable.
Degrade by surface degradation without the need for catalysts.
Aliphatic (CH2 in backbone and side chains) polyanhydrides degrade
within days.
Aromatic (benzene ring as the side chain) polyanhydrides degrade over
several years.
Excellent biocompatibility.

17. Drug loaded devices prepared by compression molding or
microencapsulation.
Suitable for short term drug delivery.
Used for vaccination and localized tumor therapy.
3) polyphosphazenes
Its hydrolytic stability/instability is determined by change in side group
attached to macromolecular backbone.
Used in the construction of soft tissue prosthesis, tissue like coatings,
as material for blood vessel prosthesis.
Used for immobilization of antigen or enzyme.
Use for drug delivery under investigation
Based on side chain these are of 3 types:
Hydrophobic phosphazenes
Hydrophilic phosphazenes
Amphiphilic phosphazenes
4) Polyaminoacids
Aminoacid side-chains offer sites for drug attachment.
Low-level systemic toxicity owing to their similarity to naturally
occurring amino acids.
Investigated as suture materials.
Artificial skin substitutes.
Limited applicability as biomaterials due to limited solubility and
processibility .
Drug delivery (difficult to predict drug release rate due to swelling)
Polymers containing more than three or more amino acids may trigger
antigenic response.
Tyrosine derived polycarbonates developed as high-strength degradable
orthopedic implants.
5) Poly (hydroxy alkanoates)-PHAs
PHAs are produced by a wide range of microorganisms, including
Pseudomonas, Bacillus, Rhodobacter, cyanobacteria and marine algae,
using a range of carbon sources.

18. PHAs degrade via a variety of mechanisms:
In bacteria: enzymatic hydrolysis
In animals or in the environment: enzymatic or chemical hydrolysis
Natural biodegradable polymers
Natural polymers are an attractive class of biodegradable polymers as
they are:
Derived from natural sources
Easily available
Relatively cheap
1) Collagen
Collagen is the most widely found protein in mammals and is the major
provider of strength to tissue.
The number of biomedical applications in which collagen have been
utilized is too high; it not only has been explored for use in various
types of surgery, cosmetics, and drug delivery, but also in bioprosthetic
implants and tissue engineering of multiple organs as well.
It is used as sutures ,Dressings, etc.
Disadvantages
Poor dimensional stability. Variability in drug release kinetics.
Poor mechanical strength.
Applications:
Majorly used in ocular drug delivery system
2) 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.
Applications:
Albumin micro-spheres are used to deliver drugs like Insulin,
Sulphadiazene, 5-fluorouracil, Prednisolone etc.
It is mainly used in chemotherapy, to achieve high local drug
concentration for relatively longer time

19. 3) Dextran
Dextran is a complex branched polysaccharide made of many glucose
molecules joined into chains of varying lengths.
It consists of α-D-1,6-glucose-linked glucan with side-chains linked to
the backbone of Polymer. Its Mol.wt ranges from 1000 to 2,00,000
Daltons.
Applications:
Used for colonic delivery of drug in the form of gels.
4) Gelatin
Gelatin is a mixture of peptides and proteins produced by partial
hydrolysis of collagen, extracted from the boiled bones, connective
tissues, organs and some intestines of animals. Gelatin is an irreversible
hydrolyzed form of collagen, physicochemical properties depends on
the source of collagen, extraction method and thermal degradation.
Applications:
Employed as coating material.
Gelatin micro pellets are used for oral controlled delivery of drugs.
5) Chitosan
Chitosan is a linear polysaccharide composed of randomly distributed
β-(1-4)-linked D-glucosamine (deacetylated unit) and N-acetyl-D
glucosamine (acetylated unit).
It is made by treating shrimp and other crustacean shells with the alkali
sodium hydroxide. Chitin is the second most abundant agro-polymer
produced in nature after cellulose.
Chitosan has a number of commercial and possible biomedical uses. It
can be used in agriculture as a seed treatment and bio pesticide, In
industry, it can be used in a self-healing polyurethane paint coating. In
medicine, it may be useful in bandages to reduce bleeding and as an
antibacterial agent.

20. List of Biodegradable Polymers used in pharmaceutical purpose

21. CHARACTERISTICS OF Biodegradable POLYMER
 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.
 Polymer degrades in vivo to release the drug
 Simple release mechanism, but difficult to obtain fine control over
degradation
 Does not invoke an inflammatory or toxic response.
 It is metabolized in the body after fulfilling its purpose, leaving no
trace
 Absence of carcinogenicity
 Absence of teratogenicity
Advantages of biodegradable polymers
• Localized delivery of drug
• Sustained delivery of drug
• Stabilization of drug
• Decrease in dosing frequency
• Reduce side effects
• Improved patient compliance
• Controllable degradation rate
APPLICATIONS OF BIODEGRADABLE POLYMERS
• Polymer system for gene therapy.
• Biodegradable polymer for ocular, tissue engineering, vascular,
orthopedic, skin adhesive & surgical glues.
• Bio degradable drug system for therapeutic agents such as anti-
tumor, antipsychotic agent, anti-inflammatory agent.

22. • Polymeric materials are used in and on soil to improve aeration, and
promote plant growth and health.
• Many biomaterials, especially heart valve replacements and blood
vessels, are made of polymers like Dacron, Teflon and polyurethane.
Medical Applications of Biodegradable Polymers
• Wound management
Sutures, Staples, Clips, Adhesives, & Surgical meshes
• Orthopedic devices
Pins, Rods, Screws, Tacks, & Ligaments
• Dental applications
Guided tissue regeneration Membrane
Void filler following tooth extraction
• Cardiovascular applications
Stents
• Intestinal applications
Anastomosis rings
• Drug delivery system
• Tissue engineering
Biodegradable Polymeric Delivery System
A large number of the carriers have been designed for delivery of
proteins and peptides via liposome, niosome, polymeric nanoparticles,
solid lipid nanoparticles etc.
Polymer based carriers have taken much attention of the scientific
community for safe and effective delivery of proteins.
Biodegradable polymers are used through slight modifications of their
structures.
Biodegradable polymers have a great applications in pharmaceutical,
medical and biomedical engineering.

23. Biodegradable polymers are not limited to release of drugs, peptides or
proteins but are also extended to medical devices and wound dressing.
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.
Polymeric DDS devices
Particulate systems
• Nanoparticles
• Nanocapsules
• Nanospheres
• Microparticles
• Microspheres
• Microcapsules
Biodegradable Delivery Systems mechanism
Drug is physically incorporated (mixed) into a biocompatible polymer
matrix
Drug is protected by the polymer
Drug migrates from the polymer to the body
Drug is released in a controlled manner

24. After all drug is released, surgical removal of the polymer is not
necessary
Polymer contains labile bonds
Physical incorporation of a drug in a polymer-based delivery systems
are an improvement to conventional administration
Drawbacks:
Incorporate low percentages of drug
High potential for drug separation (accidental or intentional)
Drug is released with a burst
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.
Examples on uses of biodegradable polymers in pharmaceutical
market
1) Injectable Implant
Injectable implants have been developed on the basis of biodegradable
polymers.
Leuprolide (Eligard), a delivery system for prostate cancer, is
supplied as an injectable suspension that utilizes the Atrigel technology
for delivering the hormone leuprolide acetate.

25. The delivery system consists of a biodegradable (lactide-co-glycolide)
copolymer dissolved in a biocompatible solvent.
The polymer gradually loses its organic solubility once it is injected
subcutaneously.
Doxycycline (Atridox), a bio absorbable delivery system for the
treatment of periodontal disease, also uses Atrigel technology to deliver
an antibiotic, doxycycline hyclate.
2) Microspheres
3) Transdermal Patch

26. 4) Nano Carriers
• AmBisome
Drug: amphotericin B
Used as antifungal for cancer patients
Name of product: AmBisome
Approved in 1997
• Doxil
Drug: doxorubicin
Use Chemotherapy agent for ovarian cancer
Name of product: Doxcil
Reduced cardio toxicity
• Abraxane
Drug: Paclitaxel
Use Chemotherapy for breast cancer
Name of product: Abraxane
Approved in 2005 ($134 million in sales that
year)
Chemotherapeutic bound to protein nano-particle

27. 5) Protein-Polymer Conjugates
Advantages of Protein-Polymer Conjugates
Protein-polymer therapeutics are nano-sized drugs with many
advantages.

28. Protein-Polymer Conjugates on Market