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POLYMER SCIENCEPresented by Arantha j josephFirst year Mpharm

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Contents• Introduction•Definition• Classification• Application• Polymers as thickening agent• Viscosity• Solvent selection• Fabrication technologies

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1. INTRODUCTION A word polymer is a combination of two Greek

words, “Poly” means “many” and “Meros” meaning “parts or units”.

A polymer is a large molecule of which is formed by repeated linking of the small molecules called “monomers”.

More monomer molecules joined in units of long polymer.

n(CH2-CH2) (-CH2-CH2-)n ethylene polyethylene

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2. DEFINITIONS

Polymer science or macromolecular sciences is a subfield of material science concerned with polymers.

Polymer sciences has been the backbone for the development of new formulations.

Development of several applications in pharmaceutical sciences.

Monomer - is the smaller molecule(s) that are used to prepare a polymer.

Polymerization : The process of linking the repeating units (monomers) is termed as polymerization

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Classification based on SOURCE.

Classification based on BACKBONE.

Classification based on STRUCTURE.

Classification based on POLYMERISATION.

3. CLASSIFICATION

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1.Classification based on SOURCE

1.Natural polymers:- polymer that results from only raw materials that are found in nature.

Example:- Proteins, Cellulose, Starch, Rubber. Protein based: eg: albumin collagen, gelatin..polysaccharides : eg: agrose, alginate, chitosan, dextran.. 2. Synthetic polymers a. BiodegradablePolyesters : polylatic acid, polyglycolic acid, polyhydroxy

butyrate. polyanhydrides : poly sebacic acid, poly adipic acid, poly

terphthalic acid

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They are degraded in the body to the simple molecules like water and CO2 which are easily eliminated in the urine.

Mainly used for parental drug delivery system and can also be used for oral drug delivery system like liposomes, nanoparticles, microspheres etc.

Eg:- poly(glycolic acid)etc….

They are non bio degradable in the body.

Used only for oral administration .

They cannot be used for parental drug delivery of drugs.

Eg:- ethyl cellulose, methyl cellulose etc.

Biodegradable V/S Non Biodegradable

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2.Classification based on BACKBONE

Carbon chain backbone: eg: polyethylene,polypropylene,pvc,

pvp, polystyrene.

Hetrochain backbone: polyethylene oxide, polypropylene oxide.

cellulose , amylose, pectinic acid.

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3.Classification based on structure1.Linear polymers:- consist of long and straight chains. Eg:- pvc2.Branched chain polymers:- contain linear chains having some branches, e.g., low density polymer.3.Cross linked chain polymers:- formed from bi-functional and tri-functional monomers and contain strong covalent bonds e.g. bakelite, melamine.4.3Dnetwork

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4. Classification based on polymerization1. Addition polymers Formed by the repeated addition of monomer molecules possessing double or triple bonds. n(CH2=CH2) -(CH2 -CH2 )- Ethylene polyethylene2. Condensation polymers Formed by repeated condensation reaction between two different bi-functional or tri-functional monomeric units. eg: nylon 6, 6, nylon 6.

n(H2N(CH2)6 NH2) + n(HOOC(CH2)4COOH) NH(CH2)6NHCO(CH2)4CO-]n nH2O (Nylon 6:6)

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CHARACTERISTICS OF IDEAL POLYMER1) It should be versatile.2) It should possess a wide range of mechanical,

physical properties.3) It should be non-toxic 4) should be easily administered.5) It should be inexpensive 6) Easy to fabricate.7) It should be inert to host tissue.

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MECHANISM OF DRUG RELEASE FROM POLYMER

There are three primary mechanisms by which active agents can be released from a delivery system: namely,Diffusion, Degradation, Swelling .

Diffusion occurs when a drug or other active agent passes

through the polymer that forms the controlled-release device.

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The diffusion can occur on a macroscopic scale as through pores in the polymer matrix or on a molecular level, by passing between polymer chains.

In this design, a reservoir whether solid drug, dilute solution, highly concentrated drug solution

within a polymer matrix is surrounded by a film or membrane of a rate-controlling material.

The diffusion rate of the active agent can be kept fairly stable throughout the lifetime of the delivery system.

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The system shown in Figure (a) is representative of an implantable or oral reservoir delivery system, whereas the system shown in (b) is transdermal system.

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BIO DEGRADATION OF POLYMERS

Bio degradation is the chemical changes that alter the molecular weight or solubility of the polymers.

Bio erosion may refer to as physical process that result in weight loss of a polymer device.

The erosion of polymers basically takes place by two methods:-

1. Chemical erosion2. Physical erosion

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CHEMICAL EROSIONBio erosions through chemical mechanisms are explained below-Mechanism-I

It describes the degradation of water soluble macromolecules that are cross-linked to form three-dimensional network

Degradation in these systems can occur by

Type (1A)- Degradation occur at crosslinks to form soluble backbone polymeric chains. It provides high molecular weight, Water soluble fragments.

Type (1B)- Degradation occur to form water-soluble fragments. Such type provides low molecular weight, water soluble oligomers and monomers.

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Mechanism-II Describes the dissolution of water insoluble macromolecules

with side groups that are converted to water insoluble polymers as a result of ionization, Protonation or hydrolysis of the groups.

Molecular weight remains unchanged. Materials showing this type of erosion include Cellulose acetate derivatives, Co-polymers of maleic anhydride.

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Mechanism-III Describes the degradation of insoluble polymers with

liable bonds. It forms low molecular weight, water soluble molecules. Polymers undergoing this type of erosion include Poly(lactic acids) Poly(glycolic acid) and their co-polymers etc.

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PHYSICAL EROSION The physical erosion mechanisms can be characterized as

heterogeneous or homogeneous. Most polymers undergo homogenous erosion that means the hydrolysis

occur at even rate through out the polymeric matrix. loss of integrity of the matrix or polymer.

In heterogeneous erosion, also called as Surface Erosion. The polymer erodes only at the surface and maintains its physical integrity as it degrades.

Highly crystalline polymers tend to undergo heterogeneous erosion.

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DIFFERENT TYPES OF BIODEGRADABLE POLYMERS1. Lactide / Glycolide Polymers.2. Polyanhydrieds.3. Poly Caprolactone.4. Poly Orthoesters.5. Poly Phosphazenes.6. Pseudo Poly Amino Acids.7. Natural Polymers.

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1. Lactide/ Glycolide Polymers• Widely used• Bio compactable• Predictable biodegradation kinetics• Ease of fabrication• A broad spectrum of applicability is obtained by

manipulating 4 variables• Co monomer ratio, monomer stereochemistry, polymer

molecular weight and polymer chain linearity.• Crystalinity and water uptake key factor for determining

rate of in vivo degradation.

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• Solubility depends on type of monomers present.• Lactide polymers show solubility in org solvents.

Bio degradation• polymer chains are cleaved by hydrolysis monomeric

acid

eliminatesKrebs cycle

Bio erosion of Lactide Occours with no enzymatic involvement.

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Biodegradation of lactide/glycolide polymers

Poly[l-Lactide]18-24

Poly[dl-lactide]12-16

Poly[glycolide]2-4

50::50[dl-lactide-co-glycolide]

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85::15[dl-lactide-co-glycolide]

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2. POLY ANHYDRIDESOH-(-C-R-C-O-)n-H

O ODegrade from the surface.To maximize control over the release process.increased degradation by copolymerization with sebacic acid. [800]

eg:-bis carboxyphenoxypropane polymer.Degrade rapidly in basic media.[100 days in ph 10]Acidic media [3 years]

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• Cortisone acetate incorporated into several poly anhydrides

Rate of release• Poly[terepthalic acid] poly[terepyhalic acid –sebacic acid] is 50::50.

• Eg formulation containing macromolecules like insulin in poly anhydride matrices.

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3. Poly carpolactone an its copolymers• Carpolactone ring opening polymerization• Suitable for long term drug delivery more than one year.• Homopolymer degrade slowly compared to polyglycolic

acid and polyglycolic acid-co-lactic acid. • Polymerization of carpolactone can affected by four

mechanism.• Anionic, cationic, coordination and radicle.• Imp in the permeability and degradability of polymers.• Eg: steroids, tetracycline's,

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4. POLY[ORTHO ESTERS]• Acid labile linkages in their backbone.

Manipulation of hydrolysis rate .

Incoorpation

acidic /basic excipientsThough it is acid sensitive a base is used to neutralize and maintain hydrolysis under control.

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• Hydrolysis is complicated • Acid catalysis hydrolysis proceeds with the initial

protonation of an alkoxy oxygen followed by bond cleavage involving exocyclic or endocyclic alkoxy gp.• Incorporation of <1%.mol of 9,10dihydroxy stearic acid

into the polymer accelerate polymer erosion.• Long term surface erosion is desired interior of the device

is stabilized by the use of basic excipients like Mg(OH)2

Mg(OH)2+drug

Mg(OH)2+drug

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5. POLYPHOSPHAZENES• Hydrolytic stability/instability is determined by the

change in side gp.• Long chain backbone altering P and N• Side gp attached to each P.• Molecular structural change is by macromolecular

substitution reaction.Amphiphilic Phosphazenes• Attachment of hydrophilic and hydrophobic side gp.• Eg. Trifluroethoxy and methyl amino gp • Varied surface property,semipermiability.

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•Polyphosphazenes as hydrogels• Intra ocular lens •Soft tissue prosthesis•Hydrophilic coating for biomedical devices.

Water soluble bioactive polyphosphazenes.

Higher biological activity As a carrier molecule.

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6. Pseudopoly[amino acids]• Derived from simple nutrient amino acids • No toxic degradation products.Limitations antigenicity unfavourable material property. expensive.• Slowly degrading polymer• Long term therapyEg implantable multilayer contraceptive formulation.Ttrosine-derived poly[imino carbonates]

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7. Natural polymers• Deliver drug in an area.• Natural products of living organism .

Easily available.Relatively in expensive.Capable of chemical modification.

• Proteins and polysaccharides .Collagen- solid ocular inserts. Starch ,dextran ,cellulose ,inulin – drug carriers.

[ antibiotic enzymes]

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APPLICATIONS IN CONVENTIONAL DOSAGE FORMS• Tablets : - As binders

- To mask unpleasant taste - For enteric coated tablets• Liquids : - Viscosity enhancers

- For controlling the flow• Semisolids :

- In the gel preparation - In ointments• In transdermal Patches

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APPLICATIONS IN CONTROLLED DRUG DELIVERY

Reservoir Systems - Ocusert System- Progestasert System- Reservoir Designed Transdermal Patches

Matrix SystemsSwelling Controlled Release SystemsBiodegradable SystemsOsmotically controlled Drug Delivery

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Polymers as thickening agentsViscosity of polymer solution increases with concentration.Viscosity of methyl cellulose has viscosity of 80 poise Water 0.01poise2%dissolved polymer increase viscosity up to 8000fold.5% polymer viscosity- set into gel.Viscosity of polymer solution is greater than free draining

coils.Thermal agitation results molecule to be entangled.[random coils expose to large amt of solvent so Brownian motion Chain entanglement's causes reduced viscosity

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This effect is independent of shearPartial uncoiling, elongation and alignment of random coils results

in decreased viscosity. Dependent of shear.

At low shear rate.• Chain random coil.• Trap large amount of solvents.• Remain entangled.• Large flow units and high apparent viscosity.At high shear rate.• Uncoiled and elongated.• Trapping less solvents.• Usually distangled.• Small flow units and less apparent viscosity

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SOLVENT SELECTION IN POLYMERS• Primary functions of a solvent system is to dissolve or

disperse the polymers and other additives .Important considerations for ideal solvent systemShould either dissolve or disperse polymer system.Easily disperse other solution components .Should be colorless, tasteless, odorless, inexpensive,

non toxic, inert, nonflammable.Have a rapid drying rate.Have no environmental impact.

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• Most widely used solvents either alone or in combination are water, ethanol, methanol, isopropanol, chloroform , acetone, methylethyl ketone, methylene chloride.

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VISCOSITY

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Molecular weight of polymer

• Mark-Houwink equation gives a relationship between intrinsic viscosity, [η] and molecular weight, M of a polymer solution, expressed as:

• [η] = KMa • where the constants, a and K, depend on the particular

polymer-solvent system.• A value of a = 0.5 is indicative of 'theta solvent'. A value

of a = 0.8 is typical for 'good solvents'. For most flexible polymers, 0.5 ≤ a ≤ 0.8.

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Depending on the experimental techniques used, polymers may have four different kinds of average molecular weights

1. Weight average molecular weight, Mw (light scattering) 2. Number average molecular weight, Mn (colligative

properties) 3. Z-average molecular weight, Mz (centrifugation data)4. viscosity average molecular weight, Mv (viscometric behavior) and the

relative order of their values are: Mz > Mw > Mv > Mn Molecular weights based on viscosity measurements are less precise, as it depends on the solvent used, but is less expensive and easy to perform.

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FABRICATION TECHNOLOGIES

Conversion of monomers or bulk polymer into the desired form.

Methods of polymer fabrication.• 1. MOLDING • 2. EXTRUSION• 3. PREPARATION OF FILMS

1.MOLDING compression molding, injection molding, transfer molding

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MOLDING• Polymer is forced to flow into a closed container having the desired shape by the application of heat and pressure.• The closed container is used as the mold.• VARIOUS MOLDING PROCEDURES

• Compression molding• Injection molding • Transfer molding

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Compression molding• Polymer is placed in the lower half of

the heated mold ,

• Mold is closed air and excess polymer are forced out .

• Fixed pressure is applied for the selecting time.

• The mold is cooled and the object is removed with thermoset material .

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Injection molding• Polymer is first preheated and

then forced into a cold mold cavity by means of a hydraulic plunger.• The mold becomes cold.• This is a high speed method

not require a time consuming cooling step.• This methodology needed an

extremely high degree of sophistication.

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Transfer molding•As the polymer is a good insulator uniform heat transfer through out the bulk of a sizable molded object is difficult.

•May result in uneven setting of thermosetting material .

• For the reason transfer molding a combination of compression molding and injection molding are developed.

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•Heating the polymer in a semisolid cavity until it becomes semisolid and forcing by means of a ram through an orfice into the mold cavity.• Because the entire mold is heated , thermoplastic material

cannot be removed until the mold has cooled.

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Extrusion

• Polymer is propelled continuously along a screw through a region of high temp and pressure.

• It is melted and comparted and finally forced through a die to give the final object.

• Procedure is useful for preparing rods , tubes , channels and sheets.

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PREPARATION OF FILMSMETHODS INCLUDES,

• MELT FABRICATION OR CALENDERING

• SOLUTION CASTING

• POLYMERISATION IN SITU

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MELT FABRICATION OR CALENDERING• Films can be made through a suitably shaped disc or

extrusion.

• By first extruding the `tube and then expanding the hot tube by compressed gas into a tube of thin films.

• As in calendaring polymer is squeezed into a thin film between healed rollers

• Films can also be produced by melt pressing where the polymer is placed between two melted plates and the plates then placed between two heated plates.

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SOLUTION CASTING

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•Polymer is dissolved in a suitable solvent to form a viscous solution .•The solution is then spread on a flat non adhesive

surface.•Solvent is slowly evaporates .

•The resultant polymer is peeled from the surface .

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POLYMER IN -SITU•polymerization inside a suitable mold.

•useful for the preparation of rigid polymers

•particularly sheets of cross linked polymers.

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BIBLIOGRAPHY

• file:///D:/polymerization/polymers%20with%20biodegradable.htm • file:///D:/polymerization/Polymerization.htm • Vishakha K et AL, Natural polymer- a comprehensive

review. International journal of research in pharmaceutical and biomedical sciences.Dec-2012;3(4):1597-1599.• The Theory And Practice Of Industrial Pharmacy, Lachman

/Lieberman; Fourth Edition, Pg: No- 365-376• Controlled Drug Delivery, Concepts And Advances; Suresh P.

Vyas,pg No-98-107• Controlled And Novel drug Delivery, N.K.Jain ; Pg No-

365,27,31,67

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