SEMINAR ON

POLYMER SCIENCE

SUBMITTED TO :

DR. R. V. KULKARNI

(M.PHARM, Ph.D)

SUBMITTED BY:

ROSHNIKUMARI PATEL

1ST YEAR M.PHARM

DEPT. OF PHARMACEUTICAL TECHNOLOGY

2014-2015

CONTENTS:

INTRODUCTIO

POLYMER CLASSIFICATION

APPLICATION OF POLYMER IN

FORMULATION OF CONTROLLED DRUG

DELIVERY SYSTEM

BIODEGRADABLE AND NATURAL POLYMER

ITRODUCTION:-

The word polymer is derived from greekword“Poly” means “many”“Meros” means “parts”.The basic unit is known as monomer.

Definition:

Polymer is composed molecule with large molecule mass, composed of repeating structural units or monomers connected by covalent chemical bonds.

The process used for this is known as “polymerization”.

IDEAL CHARACTERISTICS :

Should be inert.

Should be compatible with environment.

Should be non toxic.

Easy and inexpensive to fabricate dosage form.

Should have good mechanical strength.

Should be inexpensive.

Factors that affects physical properties of polymer:

Degree of polymerization

Molar mass distribution.

Crystallinity.

Branching.

Stereo regularity : isoelectric arrangement of function group of backbone of carbon skeleton.

Strength may vary with temperature and formulation.

POLYMERIZATION:

The use of heat , pressure or a chemical catalyst to link monomer material into polymer chain.

Polymerization is a process of linking of small molecule together .

These small molecules are called monomers.

These monomer are linked together in different ways to form: Linear polymers Branched polymer Cross linked polymer

Linear polymer or branched polymer :

They are also known as thermoplastic materials.

They flow when heated .

They can be fabricated by the application of heat and

pressure.

They are soluble in certain solvents.

Example: Polyesters, polyamides, etc

Cross linked polymers:

They are also known as thermosetting polymer.

They do not flow when heated .

They can not be fabricated by the application heat and pressure.

Since all the polymer chain are interconnected by the covalent cross links these polymers can not be dissolved and only swell to the extent allowed by the cross linked density.

Example : Bakelite, phenol formaldehyde polymers, resins, urea formaldehyde polymer.

Classification of polymers:

Polymers are classified based on :•Depending on the way by which monomer are linked•Method of polymerization•Mechanism of polymerization•Origin of polymer•Degradability of polymer•Based on composition

1. Depending on the way by which monomers are linked:•Linear polymer•Branched polymer•Cross linked polymer

2. Based on composition:•Homo polymer•Co polymer

3. Method of polymerization:Addition polymer

Condensation polymer

4. Mechanism of polymerization:Chain polymerizationStep growth polymerization

5. Origin of polymer:Natural polymerSemi-synthetic polymer

6. Degradability of polymer:Synthetic polymerBiodegradable polymernon Biodegradable polymer

METHOD OF POLYMERIZATION:-Here the polymers are classified depending upon the method of

polymerization:-

•Addition polymers

•Condensation polymers

ADDITION POLYMERS:-•In this the repeating units of the polymers have the same

molecular formula as the monomers.

These are prepared by the polymerization of the monomers

bearing one or more double or triple bonds or by the ring

opening reactions of the cyclic structures

E.g. Low Density Polyethylene(LDPE), High Density

Polyethylene(HDPE),Poly Vinyl Chloride (PVC),Poly Styrene

(PS), Poly Tetra Fluoro Ethylene (PTFE or TEFLON),Poly

Vinyl Acetate (PVAc) etc

CONDENSATION POLYMERS:-

These are formed by the successive reactions of the

functional groups.

Since the by-product formed is a smaller molecule, the

repeating units of the polymers have fewer atoms than the

monomers.

Examples: Polyesters like Dacron, Mylar etc. Polyamides

like Nylon 6, Nylon 66, Perlon , Kevlar, Nomex etc.

Polyurethanes like Spandex etc.

Polyamide: Nylon

Based on composition:

Homopolymer:

Eg: polythene

Polystyrene

Like a-a-a-a

Copolymer :

Eg: silicon

Ethyl cellulose

Like a-b-a-b-a-b

MECHANISM OF POLYMERIZATION:-

Here the polymers are classified depending upon the

mechanism by which they are formed:

•Chain (Addition) polymerization

•Step growth (Condensation )polymerization

CHAIN (ADDITION)POLYMERIZATION:-

•In this the polymerization reaction proceeds via discrete

initiation, propagation and termination steps.

•Once the polymerization stars, each polymer chain

undergoes rapid preferential growth in terms of molecular

weight with a steady decrease in monomer concentration.

Examples: Vinyl polymers were probably the first to be

synthesized in this manner, when in 1839 Simon reported

the conversion of styrene to some gelatinous mass, Low

Density Poly Ethylene (LDPE), High Density Poly Ethylene

(HDPE), Poly Vinyl Chloride (PVC), Poly Styrene, Poly

Tetra Fluoro Ethylene (PTFE or TEFLON), Poly Vinyl

Acetate (PVAc) etc.

There are several different techniques of synthesis

depending on the active site. These are:

Active site Synthesis technique

Free radicals Free radical polymerization

Carbanions Anionic polymerization

Carbonium ions cationic polymerization

Coordination bonds with

transition metals

Ziegler-natta polymerization

STEP GROWTH (CONDENSATION)

POLYMERIZATION:-

In this there are no discrete initiation, propagation,

termination steps

Here the reaction proceeds via specific reactions between

the functional groups and thus any two molecular species

with appropriate group react.

The molecular weight of the polymer increases steadily

throughout the reaction and monomer disappears early in the

reaction.

Examples: Polyesters like Dacron, Mylar etc. Polyamides

like Nylon 6, Nylon 66, Perlon, Kevlar,Nomex etc.

Polyurethanes like Spandex etc.

KEVALAR

NOMEX

SPANDEX

ORIGIN OF POLYMERS:

Here the polymers are classified depending upon their

origin.

Natural polymers:

Example: Gelatin, Collagen etc.

Semi synthetic polymers:

Example: EC,HEC, HPMC,HPC etc.

Synthetic polymers:

Example: PGA, PLA etc.

DEGRADABILITY OF POLYMERS:

Here the polymers are classified depending upon their ability

to degrade.

•Biodegradable polymers: Example: Natural polymers like

gelatin, collagen etc and Synthetic polymers like PGA, PLA

etc.

•Non-biodegradable polymers: Example: Semi synthetic

polymers like EC, HEC, HPMC, HPC etc.

Importance:•Polymers are used as carrier materials in the formulation of

controlled drug delivery systems.

•The selection of the polymer depends upon the intended use

and the desired release profile.

BIODEGRADABLE POLYMERS:

These are polymers consisting of monomers

linked to one-another through functional groups and

have unstable linkages in their backbone.

These polymers are biologically degraded or eroded

into oligomers or monomers that can be metabolized and

excreted :

By the enzymes introduced in-vitro(or)

By the enzymes generated by surrounding living

cells(or)

By the enzymatic process.

There are three basic approaches which govern the design

of controlled drug delivery systems containing bio-

degradable polymers:

Erosion of the polymer surface with concomitant release

of the physically entrapped drug.

Cleavage of the covalent bond between the polymer and

the drug, occurring at the polymer bulk or at the surfaces

followed by the diffusion drug release.

Diffusion controlled release of the physically entrapped

drug, with bio absorption of the polymer delayed until drug

depletion.

These polymers are applicable to a wide range of drugs.

Ideal characteristics of Biodegradable

polymer:-

They should be biocompatible-(shape, surface, and

leachable)

They should be bio absorbable-(degradability profile,

reabsorption of degradation products.)

They should be bifunctional-(physical, mechanical and

biological).

They should be stable-(processing, sterilization and

storage).

Mechanism of release through biodegradable

polymers:

Diffusion

Swelling

Erosion

CLASSIFICATION OF BIODEGRADABLE

POLYMERS:

•Natural polymers:

Proteins: Example: Albumin, Collagen, Gelatin etc.

Polysaccharides: Example: Sodium alginate, Chitin,

Chitosan, Cellulose, Dextran, Insulin, Hyaluronic acid,

Starch

•Synthetic polymers:

Aliphatic polyesters: Example: Poly-Glycolic Acid

(PGA), Poly Lactic Acid (PLA), Poly-Hydroxy Butyrate

(PHB), Poly-β-Malic Acid (PMA) etc.

Poly Phospho Esters

Poly Anhydrides

Poly Phosphazenes

Pseudo Amino Acids

Poly Ortho Esters

NATURAL POLYMERS:-

The use of natural biodegradable polymers to deliver

drugs continues to be an area of active research despite

the advent of synthetic biodegradable polymers.

Natural polymers remain attractive primarily because,

They are an attractive class of biodegradable polymers.

They are derived from natural sources.

They are easily available.

They are relatively cheap.

They qualify for a number of chemical modifications.

They can be a protein or a polysaccharide in chemical

origin.

Modified natural polymers are natural polymers altered to

improve their biodegradation profile that can be achieved

by chemical modifications or enzymatic alteration.

Examples:

Proteins:

•Albumin

•Collagen

•Gelatin

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.

SERUM ALBUMIN AND ALBUMIN:-

Advantages:

It is easily available.

It is biodegradable into natural products.

Non-toxic and non-antigenic.

The release pattern of drugs from albumin micro-

spheres is biphasic initial burst release is followed by a

comparatively slower first order release.

Factors affecting drug release from albumin

micro-spheres:

Physicochemical properties and the concentration of the

drug.

Interaction between the drug and the albumin matrix.

Size and density of microspheres.

Nature and degree of cross-linking.

Presence of the enzymes and pH of the environment.

Uses:-

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.

It is the primary structural protein.

It occurs in the animal tissue as aligned fibres in

skin, connective tissue and the organic substances of

the bone.

Collagen:-

Advantages:It is easy to isolate and purify in large quantities.

It is biocompatible and non-toxic.

It has well established physicochemical, structural and

immunological properties.

It is easy to process collagen in various forms.

Disadvantages:Poor stability.

Variation in drug release kinetics.

Low mechanical strength and elasticity.

To overcome poor mechanical properties and non-

reproducible delivery rates of collagen, collagen shields

(which look like the contact lens) are prepared from

intact porcine sclera tissue. They are spherical in shape,

having a thickness of 0.027mm-0.071mm.

Uses:Collagen shields are used in the ocular

drug delivery system of drugs like Pilocarpine,

Gentamycin etc.

Gelatin:It is a heterogeneous product obtained by irreversible

hydrolytic extraction of treated animal collagen.

This converts tough fibrous collagen into a water soluble

protein.

The physicochemical properties of gelatin are dependent

on the source of collagen, the extraction method, pH value,

thermal degradation and electrolyte content.

Advantages:It is easily available.

It has low antigenic profile.

It binds poorly to the drug molecules.

It reduces the chances of drug degradation as low

temperature is used for the preparation technique.

Uses:

It is used as a matrix and as a coating material

in drug delivery systems.

Gelatin micro-pellets can be prepared for oral

controlled drug delivery systems.

Polysaccharides:

Sodium alginate

Chitin

Chitosan

Dextran, etc.

Sodium alginate:

Alginates are hydrophilic carbohydrates obtained from

various species of brown sea weeds, by the use of dilute

alkalies.

They can be easily fabricated into particulate systems.

Advantages:

Since the use of organic solvents and high

temperature is not required even viable bacteria and

viruses can be employed.

It protects the antigen and the vaccines against

degradation in GIT.

It acts as an adjuvant.

Uses:

Alginates are particularly used as carriers of peptides

and other sensitive drug molecules since particulate

carriers can be easily prepared in aqueous solution at

room temperature.

Alginate micro-spheres are efficiently used for oral

delivery of vaccines.

Chitin:It is a linear poly-cationic polymer of N-acetyl-D-

glucosamine units linked by β-D (1-4) bonds.

It is insoluble in common solvents.

It has low chemical reactivity.

Industrial sources of chitin are: shells of lobster shrimp

and crab.

Chitosan:It is a principle derivative of chitin and is obtained by

alkaline deacetylation.

Both chitin and chitosan are distinguished by their

solubility profile in dilute aqueous acid solutions.

Drug diffusion from chitosan matrix can be controlled

by employing a cross-linking agent like glutaraldehyde

Characteristic properties of chitosan:

It has antacid, antiulcer, hypocholesterolemic and wound

healing properties.

Haemostatic and spermicidal properties owing to its ability

to bind strongly with the mammalian cells by the virtue of

their poly-cationic character.

Presence of reactive functional group and cationic

character opens up possibilities for their application in

controlled drug delivery systems.

It is biodegradable, biocompatible and non-toxic.

It has gel forming ability at low pH and so is a suitable

polymer for oral sustained release drug delivery system.

The chitosan matrix formulation floats and gradually

swells in acidic medium.

It also has an antitumor activity and so is used for the

treatment of cancer.

Factor affecting drug release from chitosan

micro-spheres:

Particle size and density of micro-spheres.

Nature and degree of cross-linking.

Physicochemical properties and the concentration of

the drug.

Type of chitosan.

Viscosity of lipophilic phase.

Uses:

It is used as directly compressible excipient.

It is used to decrease the angle of repose and hence

improve the flow properties of conventional excipients like

mannitol, starch, lactose etc.

It is used as a diluent, binder, lubricant and a potential

disintegrant due to its water uptake properties.

Ulcerogenic drugs like aspirin can be effectively

administered with chitosan as it has a gel forming property at

low pH and also has antiulcer and antacid properties.

It is used to reduce the gastric mucosal injury associated

with Diclofenac sodium.

Liposome Stabilization.

Imparts targeting potential to the Liposome owing to

its Mucoadhesive property

Chitosan 5-fluorouracil conjugates have lower side

effects than native 5-fluorouracil.

The film forming ability of chitosan can be employed

for the development of contact lenses.

It is also used in ocular bandage lenses, which is used

as a protective device for acute or chronic traumatic

eyes.

It interacts with liposome and results in:

Dextran:

It is a polymer of glucose.

It is prepared by subjecting the sucrose to the action

of the bacterium Leuconostoc mesenteroides.

The crude high molecular weight Dextran which is

formed is hydrolyzed and fractionated to yield Dextran

of desired molecular weight.

. It is used in the form of a gel for colonic delivery of

drugs

Synthetic polymers:

Most attractive class of polymers.

Biocompatible and versatile in terms of physical,

chemical and biological properties.

Examples:

Aliphatic polyesters: PGA, PLA etc.

poly Phospho Esters (PPE)

Poly Ortho Esters (POE), etc.

PGA and PLA:

They are also known as poly-glycolic acid and poly-

lactic acid respectively.

They are the simplest linear aliphatic polyesters.

The copolymers of glycolic acid and both L-Lactic

acid and DL-Lactic acid are used for the development of

drug delivery systems.

The in-vitro degradation profile is determined by the

water uptake capacity and the crystallinity of the

polymer.

The rate of hydration and subsequent degradation can

be increased by increasing the glycolic acid ratio and the

lactic acid ratio in the copolymer respectively.

Solubility of polymers in common solvents is of prime

importance while formulating delivery systems.

Poly-glycolic acid and glycolic acid rich copolymers

are insoluble in most organic solvents except highly

fluorinated organic solvents like Hexafluoroisopropanol.

Homo-polymers based on D-, L- and DL-Lactic acids

are soluble in dioxane, ethyl acetate, halogenated

hydrocarbons and tetrahydrofuran,

Poly-lactic acids offer broad spectrum activity and

versatility by changing:

Monomer stereochemistry

Co-monomer ratio

Polymer chain linearity

Polymer molecular weight

Biodegradation:

PGA/PLA chains are cleaved by hydrolysis to form

monomeric acid units.

They are eliminated in-vivo through Krebs ‘cycle as

CO2 and in urine.

PGA/PLA on hydrolysisGlycolic acid /Lactic

acidKrebs’s cycle CO2+Excreted in urine.

Formulation Techniques:

PGA/PLA micro-spheres can be prepared by:

Solvent evaporation

Phase separation

Fluidized bed coating

Implants can be prepared by:

Compression moulding

Injection moulding

Screw extrusion method

Precaution:First dry the bulk polymer and the bioactive drug at ambient

temperature under vacuum prior to processing.

The process equipment must be covered with dry N2

blankets.

Drug release from the polymer:

Leaching of the contents from the polymer.

Bio-erosion of the matrix.

Poly-phospho esters:

1. These are referred to as polyphosphates,

polyphosphonates or polyphosphates depending upon the

nature of side chain attached to phosphorus.

2. These polymers are:

•Versatile

•Have good physicochemical profile

•Biocompatible

3.These polymers are used to deliver paclitaxel and

cisplatin in the form of micro-spheres.

Poly-ortho esters:

•These polymers have acid-sensitive linkages in their

backbones and allow easy manipulation of hydrolysis rate

by physical incorporation of acidic or basic excipients into

the matrix.

•The hydrolysis of these polymers is predominantly

confined to the outer surface and the resultant surface

erosion allows excellent control of the release of the

incorporated therapeutic agent.

•Hydrolysis takes place via initial protonation of alkoxy

oxygen followed by bond cleavage involving exocyclic or

endocyclic alkoxy group.

•Since these are acid sensitive and are stable in base control

over erosion can be achieved by:

•Use of an acidic excipients to accelerate rate of

hydrolysis (or)

Use of a base to stabilize the interior of the device.

These are prepared by trans-esterification.

Implants and oral drug delivery systems can be

developed

Non-Biodegradable Polymers:

Examples:

•Ethyl cellulose

•Hydroxyl Propyl Methyl Cellulose

•Ethylene Vinyl Acetate

•Poly-ethylene oxide, etc.

Applications of polymer in formulation of

controlled drug delivery system:

ORAL DRUG DELIVERY SYSTEM

TRANDERMAL DRUG DELIVERY SYSTEM

OCCULAR DRUG DELIVERY SYSTEM

OTHER APPLICATION

1.ORAL DELIVERY SYSTEM:Here the drug gets released at controlled rate when administered orally. for that several mechanisms are involved.

•Osmotic pressure controlled GI deliver system.•Gel diffusion controlled GI delivery system•Mucoadhesive GI delivery system

•Osmotic Pressure Controlled deliverysystem:Semi permeable membrane made from biocompatible polymerse.g. cellulose acetate•Gel diffusion controlled delivery system:Fabricated from gel forming polymerse.g. CMC.

•Mucoadhesive drug delivery system:It is capable of producing an adhesion interaction witha biological membrane.e.g. carbopol.

2.TRANSDERMAL DRUG DELIVERY

SYSTEM:Mostly used when the medicaments are applied

on topical route. It is easily removable when termination of treatment is needed or else in case of condition of toxicity is seen.e.g. Transdermal patch of scopolamine, nitro glycerin

3. OCULAR DRUG DELIVERY SYSTEM:

It allows prolonged contact of drug with corneal surface of eye.

Highly viscous suspension and emulsion are served to have such purpose but these preparations don’t achieve this purpose at a controlled rate.

Many ocular drug delivery formulations developed which continuously release the drug at a controlled rate

The best example is ocular insert/ocusert

developed to delivered pilocarpine in the

treatment of glaucoma

Example of pilocarpine ocusert

4.Other applications:

Drug Delivery and the Treatment of Diabetes: Here the polymer will act asBarrier between blood stream and insulin

example of polymer- N,N-dimethylaminoethylmethacrylateor polyacrylamide.

Drug delivery of various contraceptivesand hormones:

Example: Medroxy progesterone acetate releasingvaginal contraceptive rings

Polymers can be used as film-coatings to disguise

the unpleasant taste of a drug to enhance drug stability

and to modify drug release characteristics.

Lactic acid and glycolic acids are widely used in

drug delivery research due to their versatility in

polymer properties.

Poly-anhydrides are used in CDDS because of their

unique property of surface erosion.

Poly-caprolactone is used with other polymers in

designing CDDS.

Poly-phosphazenes are used in the formulation of

Melfalan matrix systems.

Pseudo-amino acids are used in controlled release

formulations.

Hyaluronic acid is used in controlled release

ophthalmic preparations

Various uses of polymer in

pharmaceutical sciences:

Formulation of matrix tablets

Formulation of nanoparticles

Formulation of solid dispersion

In targeted drug delivery system

In a preparation of Polypeptide Vesicles for drug

Delivery

In a formulation of Cross linked Polymer micelles

for Cancer Therapeutics

EVALUATION OF POLYMER:

Differential scanning calorimetry (DSC)

Gel permeation chromatography (GPL)

Light scattering

1)DIFFERENTIAL SCANNING

CALORIMETRY:

This technique can make

calorimetric measurements of heat capacity and

energies of phase transitions. In case of polymer a

glass transition can be observed as a discontinuity

in the heat capacity.

The degree of crystallinity of

semi –crystalline polymers can be determined

from the heat of melting temperature can easily

be measured and these are often found to depend

on heating rates.

2)GEL PERMEATION

CHOMATOGRAPHY (GPL):This chromatographic technique

passing a solution of polymer through a coumn

with porous packing . The small molecules are

retained for longer on the column and hence

eluted and detected after the large molecues.

The polymer can be detected as they are

eluted by measuring changes in the refractive

index , infrared absorption, viscosity or light

scattering detectors connected to the output

stream and give a direct measure of the absolute

molecular size.

3)LIGHT SCATTERING :This method determines the size and the or

mobility of colloides and polymer . It can be

divided into two different techniques

•Static light scattering in which the angular

distribution of scattered intensity is measured to

determine the size of scattering object.

•Dynamic light scattering in which a correlation

function of scattered photons is measured and is

measured and if often used to determine mobility

and to deduce a hydrodynamic size.

References :Targeted and controlled drug delivery by

S.P.VYAS & R.K.KHAR

Robinson , CDDS

N.K.JAIN, CDDS

Encyclopedia of controlled drug delivery

system

www.google.com