BIO-COMPATIBLE AND BIO

-DEGRADABLE POLYMERS

CONTENTS
DRUG RELEASE MECHANISMS THROUGH
POLYMER MATRIX
INTRODUCTION
POLYMERS AND ITS APPICATIONS
CONCLUSION
REFERENCES

POLYMERS

Macromolecule that is formed by linking of repeating units through

covalent bonds in the main backbone
Properties are determined by molecular weight, length, backbone
structure, side chains, crystallinity Resulting macromolecules have
huge molecular weights

Terminology:

mer: a unit
monomer: one unit
dimer: two units
trimer: three units
tetramer: four units
polymer: many units
oligomer: few units fixed in size

Entrapment or Encapsulation

During the 1970, scientists first began to encapsulate and entrap

drugs within polymers

Encapsulation involves surrounding drug molecules with a solid

polymer shell

drug

polymer

Entrapment involves the suspension of drug molecules within a

polymer matrix.

Drug
polymer

Drug Release By Diffusion

Early encapsulation and entrapment systems released the drug

from within the polymer via molecular diffusion
When the polymer absorbs water it swells in size
Swelling created voids throughout the interior polymer
Smaller molecule drugs can escape via the voids at a
known rate controlled by molecular diffusion (a function of
temperature and drug size)

Add
water

Add
time

Drug Release By Erosion

Modern delivery systems employ biodegradable polymers
When the polymer is exposed to water hydrolysis occurs
Hydrolysis degrades the large polymers into smaller
biocompatible compounds

Bulk erosion process

Polymer

Surface erosion process

Water attacks bond

mer mer mer mer mer mer mer mer mer

mer mer mer mer mer

mer mer mer

mer mer mer mer mer mer mer mer mer

Bulk Erosion
(e.g. poly lactide, polyglycolic acid)

These small compound diffuse out of the matrix through the

voids caused by swelling
Loss of the small compounds accelerates the formation of voids
thus the exit of drug molecules

Add
water

Add
time

Surface Erosion
(e.g., polyanhydrides)
When the polymer is exposed to water hydrolysis occurs
Hydrolysis degrades the large polymers into smaller
biocompatible compounds
These small compound diffuse from the interface of the polymer
Loss of the small compounds reveals drug trapped within
Note these polymer do not swell.

Add
water

INTRODUCTION

Biocompatible polymer lacks adverse response, immunogenicity

histocompatability of the material upon injection.

Biodegradation relates to the breakdown of the polymer into its

monomeric units upon coming contact with bodyfluids, enzymes.

Biocompatible and Biodegradable which are used as interchangeable

terms to polymers.

The term biocompatible polymers are used to denote all transient

polymeric materials, regardless of their chemical type, origin, and mode
of clearance or absorption from the application site.

Biocompatible polymers can be derived from

1 Naturally occurring polysaccharides and proteins,
2 Totally synthetic polymers, or
3 Combinations of natural and synthetic components

POLYSACCHARIDES

Acacia, known as gum arabica, is widely used as an emulsifier and

a viscosity modifier

Tragacanth is widely used as a natural emulsifier in conjunction

with acacia and is an effective viscosity modifier for suspension
formulations.

It contains a variety of methoxylated acids that upon contact with

water become a gel.

Xanthan gum is an anionic, water-soluble polysaccharide obtained

from a pure culture fermentation of Xanthomonas camprestris

It has been used to develop sustained-release dosage forms

because the high-molecular-weight gum dissolves slowly in water.

CELLULOSE

Cellulose is a polysaccharide; it is a natural polymer . It consists of

glucose repeating units, bridged with oxygen. Each repeating unit has
three hydroxyl groups per molecule of glucose.

Its high crystallinity results from the strong

hydrogen bonding

Microcrystalline cellulose

Two types of applications of microcrystalline cellulose are dry powders

and aqueous dispersions.
Microcrystalline cellulose are used for pharmaceutical applications as
fillers, binders ,disintegrants, lubricants, and flow aids.
Microcrystalline cellulose is a good candidate for fillers because it is
chemically inert, free from organic and inorganic contaminants, and
compatible with other active drugs and excipients.

Cellulose acetate alone or in combination with cellulose triacetate or

cellulose butyrate is used as a semipermeable membrane for
osmotic pumping tablets, primarily in controlled release systems.

The permeability of the membrane can be further modulated by

adding water-soluble excipients to the cellulose esters.

Water-soluble hydroxypropylmethyl cellulose and water-insoluble

cellulose acetate are further treated with phthalic anhydride or
succinic anhydride to yield hydroxypropyl methylcellulose phthalate,
cellulose acetate phthalate, and hydroxypropylmethylcellulose
acetate succinate.

These polymers are used as enteric materials and are water soluble
or insoluble above or below a specific pH, respectively.

Chitin and chitosan

Chitosan is a useful derivative of chitin, which is the second most

plentiful natural polymer.

Crustaceans, Insects: exoskeleton

Major source
(currently: shellfish waste: animal feed)

Chitin is a naturally occurring polysaccharide consisting of amino

sugars. It is a natural polymer formed of repeating monomer units of (1-4)-2-acetamido-2-deoxy-D-glucose.

Chitin

Chitosan

Insects

Shrimp

Fungi

Fungi

Chitosan and its derivatives have been applied to enhance the

absorption of proteins (e.g., insulin) and polypeptides
(e.g.,buserelin).

N-Trimethyl chitosan chloride exhibits opening of the tight junctions

of the intranasal and intestinal epithelial cells so that the transport of
hydrophilic compounds is increased through the paracellular
transport pathway.

Chitosan and hydroxypropyl chitosan were found to be

enzymatically degraded so that they can be used for implantable
controlled-release dosage forms.
chitosan and chitin have been used in numerous areas such as
wound dressing, cholesterol control, food stabilization, hair/skin
care, and cell/enzyme immobilization.artificial sskin

Alginates

Alginate is a linear polysaccharide (MW 47,000 to 370,000) extracted from

brown seaweed (mainly Laminaria) consisting of D-mannuronic acid and Lguluronic acid residues.

Sodium alginate forms a flexible, translucent gel upon contact with Calcium
chloride solution (i.e., cross-linking) by replacing the hydrogen bonding

.The longer the cross-linked gel remains in the calcium chloride solution, the
more rigid the gel that will be obtained. The cross-links can be broken by
placing them into brine..

Sodium alginates and propylene glycol alginate are used for a variety of
applications such as cell immobilization (e.g., encapsulation of pancreas
cells), wood dressings, antacids (e.g.,Gaviscon), dental impression
materials, pharmaceutical excipients, and drug delivery

GELATIN

There are two types of gelatin, depending on the source material

and the preparation
1 Type A is derived from an acid process, primarily of pigskin
2.Type B is derived from alkaline or lime and acid processes,
primarily of cattle or calf skins and bones where the collagen is older
and densely cross-linked
The film-forming property of gelatin finds many applications in
pharmaceutical products (e.g., hard and soft capsules).
Gelatin is amphoteric and amphiphilic and thus has limited
emulsifying properties (HLB 9.8) (e.g., whipped cream) that can be
used in water-in-oil emulsions
Gelatin is also used for tablets, suppositories (e.g., glycerinated),
hemostatics

Hydrogels
(e.g. polyacrylic acids)

Cross-linked, hydrophilic, 3-D polymer networks that are highly

permeable

Do not swell in the presence of water unless activated

Swelling activate by pH, temperature, electric field

Drug release happens via void generated & diffusion (diffusion rate
is regulated by cross-linking ratio)

mer mer mer mer

mer mer mer mer

Add water
+
activator

mer

mer

mer

mer

mer mer

mer
mer

Hydrogels have been used extensively for the controlled release of

bioactive molecules and the encapsulation of cells.

In particular, the use of hydrogels is increased for tissue

engineering for tissue repair or tissue regeneration in the body.

.Hydrogels are biocompatible

Enzyme-mediated HA (hyaluronic acid-tyramine) gel formation in

vivo shows promise for achieving effective drug therapy and tissue
regeneration.

The new materials are being examined for controlled protein

release, immunocancer therapy, and tissue engineering

Polyanhydrides
Polyanhydrides were specifically prepared in attempts to produce
surface-eroding dosage forms.
A wide variety of aliphatic and aromatic monomers have been used to
prepare surface-eroding polyanhydride polymers
Aliphatic polyanhydrides are normally prepared from dicarboxylic acids
such as adipic acid, sebacic acid (SA) and fumaric acid (FA).

The release of a number of drugs from polyanhydride matrices has

been studied including ciprofloxacin, p-nitroaniline, cortisone acetate,
insulin and a variety of proteins

In many instances drug release was reported to coincide with polymer

degradation.
Polyanhydrides shows more biocompatability

Poly(esters)
Polylactic Acid, Polyglycolic Acid, and Polycaprolactone

Poly(esters) are the best widely used biodegradable and biocompatible

materials.

There are a number of different grades of poly(lactic acid) (PLA), poly(glycolic

acid) (PGA), and copolymers of lactic and glycolic acids (PLAGA) with respect
to molecular weights and compositions.

One of the major advantages of using PLA, PGA, PLAGA, and

polycarprolactone (PCL) is that the byproducts of the biodegradation are lactic
and glycolic acids, which are chemical compounds naturally found in the
human body.

As a result, these polymers are biocompatible, have been used for surgical
sutures, and are adapted to pharmaceutical applications (especially, controlled
release of proteins and peptides).

Silicone polymers

Silicone polymers are one of the most widely used types of polymer within the medical and
pharmaceutical industries.

Silicone polymers are inorganic polymers with no carbon atoms in the backbone chain, which
is a chain of alternating silicon and oxygen atoms.

Silicone polymers are highly biocompatible, easily

fabricated, and highly permeable
to many important drugs.

Besides, they can be sterilized by heat, which is an important aspect for implantable devices.
Common silicone polymers are
1. polymethylphenylsiloxane and
2 . polydimethylsiloxane,
3 . polydiphenylsiloxane.

Most silicone polymers are synthesized by the condensation

polymerization of purified chlorosilane and water.

Dimethicones are liquid polymers having the general form

The dimethicones are prepared over a wide range of viscosity

grades. The polymers have been used as a lubricant for artificial
eyes and joints and as water repellants in lotions and creams.

Polymethylphenylsiloxanes are used as a lubricant for syringes

Glassware coated with silicone polymers is rendered so

hydrophobic that water drains easily from such containers.

Conclusion
This is the exciting time for the development of
biodegradable and biocompatible drug delivery systems.
The sustained delivery of drugs to the body has,
practically speaking,become a reality as numerous
products have passed regulatory review and proven to
be commercially successful.
New polymers continue to be developed
At the same time, new therapeutic applications are being
increasingly recognized.

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THANKU