Polymer Science

Introduction:

1. Every pharmaceutical product contains one or more polymers to improve its stability or

performance.

2. Example: Sodium CMC is used to increase physical stability of suspensions.

3. Example: Ethyl cellulose is used for enteric coating of tablets.

4. Polymers are very large molecules made up of repeat units called monomers. Structure in bracket

represents the repeat unit.

5. Carbon atoms have the capacity to bond with another and form long polymer chains. Silicone and

sulfur also has the same ability to form polymer chains.

6. Example: Poly ethylene, poly propylene, starch, gelatin, poly ethylene glycol, nylon, poly ester,

poly vinyl chloride (PVC), acacia, sodium alginate etc.

7. Example: Starch is made of 300 to 600 glucose repeat units and is shown below. The number

after the brackets indicates the number of repeat units. It is called degree of polymerization (n).

8. If n =1, it is a monomer, n=2 it is a dimer, n = 3 it is a trimer, n = 5 it is a pentamer, n = 20 to 30

it is called oligomer.

Example: Poly ethylene is made by polymerization of ethylene and is shown below.

Types of Polymers:

1. Homo chain polymers have the following back bone structures. They have the same repeat atom.

C – C – C – C – C – C – C – C – C – C – C – C – C – C – C –

S – S – S – S – S – S – S – S – S – S – S – S – S – S – S – S –

Si – Si – Si – Si – Si – Si – Si – Si – Si – Si – Si – Si – Si – Si –

2. Hetero chain polymers have different atoms in the back bone.

C – C – O – C – C – O – C – C – O – C – C – O – C – C – C –

3. Homo polymers have single monomer as repeat unit. Example: PVC has vinyl chloride as repeat

unit.

4. Co polymers have two or more monomers as repeat units.

5. Random co polymers have two or more monomers as repeat unit. Example: Poly olefin has

ethylene (E) and propylene (P) as repeat unit.

-PPEPEPPEEPPEEPPEPPPEPPEPEPEPEPEPPPEPEPEPP-

6. Alternate co polymer has two monomers alternating.

-PEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEP-

7. Block co polymer has long sequence of one monomer followed by another monomer and so on.

- PPPPPP – EEEEEE – PPPPPP – EEEEEE – PPPPPP-

8. Branched polymer has branches in the polymer chain.

9. When polymer chains are cross linked they are called as cross linked polymers. Example: Cross

linked PVP.

10. Thermoplastic polymers: These are linear or branched polymers. They melt at higher

temperatures and can be recycled. Example: Poly ethylene, PVC, Poly styrene.

11. Thermo setting polymers: They are cross linked polymers. They soften on heating, they get

destroyed before melting. They cannot be recycled. They just swell in water. Example: Bakelite,

cross linked poly styrene.

12. Natural polymers: They are obtained from natural sources. Example: wool, silk, rubber,

cellulose, starch, DNA, RNA, etc.

13. Synthetic polymers: They are produced in the labs and are called plastics. Example: Synthetic

rubber, nylon, PVC, Poly ethylene, poly propylene etc.

14. Addition polymers: They are made by addition polymerization reaction using a catalyst.

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15. Condensation polymers:

These polymers are produced by a condensation reaction between two different monomers to give a

polymer.

Ethyl alcohol reacts with acetic acid to form ethyl acetate an ester. It cannot undergo further

condensation reaction. There is no chance for polymerization.

Phthalic acid has two carboxyl groups and ethylene glycol has two hydroxyl groups. They react with

each other to form an ester. As this ester still has free functional groups, they will undergo

etherification reactions to form polymer chains. The phthalate ester will combine with another

phthalic acid molecule to form an ester which will in turn combine with another ethylene glycol

molecule and so on. As a result a polymer chain is formed.

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16. Elastomers: These polymers have elastic properties. Example: Rubber.

Molecular weight averages:

1. During the synthesis of polymers, all the polymer chains do not grow equally.

2. Hence, in a sample, the polymer chains are of different lengths and different molecular weights.

Hence molecular weight average is calculated for polymers on number basis or weight basis.

3. Molecular weight average calculation on number basis (Mn) : Consider poly styrene sample

has one small molecule A (1000 g/mole) and one large molecule B (99000 g/mole).

4. Molecular weight average = (1000 + 99000) / 2 = 50000 g/mole.

5. Molecular weight average calculation on weight basis (Mw): Consider poly styrene sample has

one small molecule A (1000 g/mole) and one large molecule B (99000 g/mole). Now we have to

give importance to the weight contribution by polymer chains A and B.

6. Weight fraction of A = (Weight of A / Weight of A + Weight of B) = 1000 / 100000 = 0.01

7. Weight fraction of B = (Weight of B / Weight of A + Weight of B) = 99000 / 100000 = 0.99

8. Molecular weight average = 0.01 x 1000 + 0.99 x 99000 = 98020 g/mole.

9. This average is better in describing the molecular weight of the polymer sample. The polymer

will have the properties of the long chain because it is dominating in the polymer sample.

10. If all the chains are of same length, Mn and Mw will be same.

11. Poly dispersity (PD): It gives an idea about how the Mn varies from Mw.

12. PD = Mw / Mn = 99000 / 50000 = 2.

13. If PD is one, it indicates that all the polymer chains are of equal size. Greater the PD value, more

the variation in polymer chains.

14. A very narrow molecular weight distribution is required for a polymer to be strong and useful in

pharmacy. Polymers are available in different viscosity grades. Polymers with small molecules

are of low viscosity grade and polymers with large chains are of high viscosity grade.

Determination of molecular weight from solution viscosity:

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1. The viscosity of a dilute polymer solution depends on the nature of the polymer, concentration of

polymer, average molecular weight of polymer, solvent, temperature and shear rate.

2. The intrinsic viscosity of a polymer solution can be used to determine the molecular weight of

polymers using the Mark – Houwink equation.

3. [η] = K Ma -------- 1

4. [η] = intrinsic viscosity, K and a are constants which depend on polymer, solvent and

temperature.

5. M = average molecular weight of polymer

6. The value of exponent “a” is between 0.6 and 0.8 and K values are between 0.2 x 10 - 4 to 8 x 10- 4

dl/g.

7. If “a” value is close to 0.8, it indicates that there is good interaction between polymer and solvent

and the solution will have high viscosity.

8. K and “a” values can be obtained from literature or books.

9. First, we prepare a series of dilute solutions of the polymer. The viscosities of the

solutions are found out using a viscometer. The following viscosity terms are

calculated and a graph is drawn to determine the intrinsic viscosity.

10. The different equations to calculate intrinsic viscosity are given below.

11. ηrel = [η / ηo] --------- 3,

12. ηsp = [ηrel – 1] ------- 4,

13. ηsp / c = reduced viscosity -------- 5

14. η = viscosity of polymer solution, ηo = viscosity of solvent, ηre = relative viscosity

15. ηsp = specific viscosity, c = concentration of polymer

16. A plot of reduced viscosity versus c will give a straight line with a y intercept

equal to intrinsic viscosity. Once, intrinsic viscosity is known, we can calculate the

molecular weight of the polymer.

Polymers as thickening agents / viscosity building agents:

1. Polymers increase the viscosity of the solvent exponentially. Example: A 2 % methyl cellulose

solution has a viscosity of 8000 centi poise.

2. They show the phenomena of Thixotropy. They are highly viscous at rest and become thin on

application of shearing stress.

3. The polymer molecules are solvated, entangled and form a three dimensional network as shown

in the below figure. They entrap the solvent within the polymer coil and show high resistance to

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flow. On application of stress / shaking, uncoiling of polymer chain takes place, solvent is freed

and the solution becomes thin.

4. The loss in viscosity is again slowly regained by Brownian motion. The polymer chains get

entangled slowly by Brownian motion and viscosity of the solution increases. This slow recovery

of the lost viscosity is called Thixotropy.

5. Thixotropy is useful in suspensions and emulsions. At rest, suspension has high viscosity due to

the three dimensional network of polymer chains and settling of drug particles is less. When the

suspension is shaken, disentanglement of polymer coil takes place, viscosity is lost and the

suspension can be poured out of the bottle easily. Once placed back in the shelf, the suspension

regains its original viscosity and will be stable.

6. Similarly, emulsions are highly viscous at rest and creaming is minimal. On shaking the

emulsion, it loses viscosity and can be poured out of the bottle easily. Once placed back in the

shelf, the emulsion regains its original viscosity and will be stable.

7. Depot injections are long acting I.M injections. They have a polymer showing thixotropy. The

injection becomes thin while passing through the needle due to break down of three dimensional

structure. In the muscle, it forms a viscous drug depot due to thixotropy and releases the drug at a

slow rate for long periods (3 days) of time. Example: Pencillin gel injection.

Polymers in solutions:

1. Selection of solvent is done using solubility parameter of polymer and solvent. The polymer and

the solvent will have good interaction if their solubility parameters are similar. The polymer

molecules will be covered by a solvent sheath and form coils entrapping the solvent. Hence, the

solution will have high viscosity due to good interaction between polymer and solvent.

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S.NO Polymer Solubility Parameter

In Hilderbands

Solvent Solubility Parameter

In Hilderbands

1 Poly ethylene 7.9 H Water 23.4 H

2 Poly propylene 8.7 H Glycerol 16.5 H

3 PVC 9.6 H Octanol 10.3 H

4 Cellulose 15.7 H Propylene

glycol

12.6 H

Example: from the above table, we can say that PVC will have good solubility in octanol.

2. In case of cross linked polymers, they swell to the maximum extent in solvents having similar

solubility parameters. Cross linked polymers do not dissolve in solvents.

Preparing polymer solutions:

1. A suitable solvent is selected for the polymer using the solubility parameter values.

2. First, the polymer is dispersed in a non solvent and is then added to the solvent to prepare a

solution. Example: Starch is dispersed in cold water and this suspension is gradually added

to hot water with stirring to prepare a starch solution.

3. Example: Methyl cellulose is less soluble in hot water and more soluble in

cold water. Hence, it is dispersed in hot water and then it is added to ice cold

water with stirring to prepare a solution.

4. In another procedure, the polymer is allowed to swell in the solvent for one

day, and then it is mixed slowly on a magnetic stirrer to dissolve the polymer

molecules. Excess mixing may break the polymer chains.

Thermodynamics of polymer solutions:

1. The thermodynamic equation for the solution process is given below.

2. G = H – T S --------- 6

3. G = Change in free energy of system due to dissolution of polymer in solvent.

4. H = Change in enthalpy of system due to dissolution of polymer in solvent.

5. S = Change in entropy of system due to dissolution of polymer in solvent.

6. If G is negative, the polymer will dissolve rapidly in the solvent. This is possible if H is

negative and S is positive.

7. If the solution process is exothermic, H will be negative.

8. During the solution process, disorder of the system increases and S will be positive. As a result,

the polymer will dissolve rapidly.

9. Entropy is a measure of disorder in a system. If the system is in an orderly manner, entropy will

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be less. If the system is in a disorderly manner, entropy is more.

10. Example: In solid state, the polymer molecules are in an orderly manner, once they are dissolved,

they move in the solvent having different coil shapes and entropy is more. Hence, the polymer

will dissolve readily, because every system wants to go from highly ordered state to disorder.

11. (Example: School children are in an order in class room. Once the school is over, they move

randomly with disorder and entropy is more.)

Gel formation, Coacervation and micro encapsulation:

1. In a polymer sol, the long chain polymer molecules are solvated by hydrogen bonding and Van

der Waal’s forces. This solvent sheath (cover) prevents the polymer molecules from coming

close to each other. They stay separately in the solution.

2. If this solvent sheath is lost due to any reason, the polymer molecules come together, attract each

other through hydrogen bond and Van der Waal’s forces, entangle with each other, cross link

with each other and form a network like structure, and phase separation / gelification occurs.

3. If the polymer is sufficient to trap the entire solvent within its network, gelification occurs.

Gelification is defined as the formation of gel, where a liquid substance is turned into solid.

4. Coacervation is defined, as the separation of polymer solution into two liquid phases, polymer

rich phase (coacervate) and a dilute liquid phase having a small quantity of polymer.

5. Coacervation is subdivided into simple and complex coacervation.

6. In simple coacervation, the polymer is salted out by electrolytes, such as sodium sulfate, or

desolvated by the addition of a water miscible non-solvent such as ethanol, or by an increase or

decrease in temperature. The added salt / non solvent will compete with the polymer chain

molecules for water, as a result, the polymer chain becomes desolvated, and phase separation

occurs.

7. Example: By adding sodium sulfate or alcohol to a gelatin sol, we can get phase separation.

8. Complex coacervation is achieved by adding a polymer of opposite charge to a polymer solution.

9. The two oppositely charged polymer chains attract each other and cross link leading to phase

separation.

10. Example: If sodium alginate sol (poly anion) is added to chitosan sol (poly cation) and mixed,

phase separation or gelification occurs.

11. Example: If calcium chloride is added to a sodium alginate sol, the calcium ions bring the

polymer chains together as shown in the below figure and phase separation / gel occurs.

12. Coacervation / phase separation principle is used in micro encapsulation technique.

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Micro encapsulation is a process of producing

particles of small size in the range 1 to 1000

μm.

a. They have a small core (liquid or solid)

surrounded by a thin polymeric wall.

b. The steps in producing micro capsules by

coacervation are:

c. Phase separation upon polymer desolvation;

Droplet formation or deposition of the

coacervate phase on a given surface.

d. Hardening of the coacervate phase.

e. Isolation of microparticles or surface-coated

material

13. Example: The fine solid drug particles are stirred in a polymer sol. Now a salt solution or non

solvent for the polymer is added gradually. Phase separation occurs and coacervate droplets are

formed on the solid drug particles. These droplets coalesce and form a coat around the drug

particle. This polymer coat can be further cross linked by adding a cross linking agent like

formaldehyde or gutaraldehyde.

14. Ionic gelation method can also be used to prepare micro particles. Example: When a solution

containing drug and sodium alginate is added to calcium chloride solution, micro particles are

produced. The calcium ions cross link the alginate to form gelled droplets. These micro particles

are filtered and dried. These micro capsules will release the drug over a long period of time.

Gels / jellies:

1. They are semisolid systems consisting of large polymer molecules interpenetrated by a liquid.

2. The long polymer chain molecules get entangled, attract each other by Van der Waals forces and

hydrogen bonds and form a three dimensional network.

3. Example: Sodium CMC forms viscous fluids at low concentrations. At higher concentrations

(2%), a gel is formed.

The concentration at which gels start forming is called critical gel point. This depends on the

nature of the polymer, its chain flexibility and its interaction with solvent.

4. Most gels are reversible. On shaking or stress the polymer chains get disentangled and the

gel becomes a fluid (sol).

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5. When polymer molecules come close, cross

linking of the polymer molecules by

covalent bonds may take place and a

permanent gel is formed.

6. Gels contract on standing and some of the

interstitial fluid is squeezed out and is called

syneresis.

7. Gels show plastic behavior. At, low stress they undergo elastic deformation or reversible

deformation. Above a particular shearing stress value, they behave like Newtonian liquids. If the

yield value is high, the gel is hard, and if the plastic viscosity is more, the gel is said to be stiff.

8. Gel-forming hydrophilic polymers are used to prepare lipid-free semisolid dosage forms,

including dental, dermatological, nasal, ophthalmic, rectal, and vaginal gels and jellies.

9. Example: Voveran gel, xylocaine jelly, gel tooth paste.

10. Gels containing drugs are useful for application to mucous membranes and ulcerated or burned

tissues, because their high water content reduces irritancy.

11. Another advantage is, these hydrophilic gels are easily removed by gentle rinsing or natural

flushing with body fluids.

12. Poloxamer and carbomer are used to produce transparent ophthalmic gel products.

13. Gels have a wide range of rigidity, beginning with a sol and increasing in rigidity to a mucilage,

jelly, gel, and hydrogel.

14. Substances that form aqueous gels are usually hydrophilic polymers capable of extensive

solvation. At certain temperatures and polymer concentrations, and, in some cases, with the

addition of ions, a three dimensional network is formed.

15. Poloxamer is a block co polymer of propylene oxide and ethylene oxide. For example, poloxamer

188 can be written as (PEO)75-(PPO)30-(PEO)75. At high concentrations (>20%), poloxamers

form thermo reversible gels; they gel on heating rather than cooling.

16. Poloxamer gels are used as artificial skin, which is helpful in treating third-degree burns. The

gels are non-toxic, and prevent loss of water, heat, and electrolytes.

17. Because of poloxamer’s inverted thermo reversibility, cool solutions can be poured onto

damaged tissue, they form gels at body temperature. The gels are easily removed by rinsing with

cool water.

18. Poloxamer gels mimic mucus and are optically clear, which makes them suitable for ophthalmic

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drug

19. Delivery. A poloxamer gel formulation containing pilocarpine showed improved bioavailability

over an aqueous solution of the drug.

20. Subcutaneous injection of insulin loaded poloxamer gels prolonged the hypoglycemic effect of

insulin in rats.

Pharmaceutical application of polymers:

1. Polymers are used in tablets as diluents, binders, and disintegrants.

2. Example: Starch – disintegrant, PVP – binder, micro crystalline cellulose – diluent, etc.

3. Polymers are used in coating of tablets. Example: ethyl cellulose is used to make enteric coated

tablets. The polymer coat dissolves in the intestine and releases the drug there.

4. Polymers are used as viscosity building agents in suspensions and emulsions to improve their

stability. Sodium CMC is a polymer which shows thixotrophy in suspensions, emulsions and

depot injections.

5. Thixotropy is useful in suspensions and emulsions. At rest, suspension has high viscosity due to

the three dimensional network of polymer chains and settling of drug particles is less. When the

suspension is shaken, disentanglement of polymer coil takes place, viscosity is lost and the

suspension can be poured out of the bottle easily. Once placed back in the shelf, the suspension

regains its original viscosity and will be stable.

6. Similarly, emulsions are highly viscous at rest and creaming is minimal. On shaking the

emulsion, it loses viscosity and can be poured out of the bottle easily. Once placed back in the

shelf, the emulsion regains its original viscosity and will be stable.

7. Depot injections are long acting I.M injections. They have a polymer showing thixotropy. The

injection becomes thin while passing through the needle due to break down of three dimensional

structures. In the muscle, it forms a viscous drug depot due to thixotropy and releases the drug at

a slow rate for long periods (3 days) of time. Example: Pencillin gel injection.

8. Gel-forming hydrophilic polymers are used to prepare lipid-free semisolid dosage forms,

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including dental, dermatological, nasal, ophthalmic, rectal, and vaginal gels and jellies.

9. Example: Voveran gel, Gel tooth paste.

10. Gels containing drugs are useful for application to mucous membranes and ulcerated or burned

tissues, because their high water content reduces irritancy.

11. Another advantage is these hydrophilic gels are easily removed by gentle rinsing or natural

flushing with body fluids.

12. Poloxamer and carbomer are used to produce transparent ophthalmic gel products.

13. Poloxamer is a block co polymer of propylene oxide and ethylene oxide. For example, poloxamer

188 can be written as (PEO)75-(PPO)30-(PEO)75. At high concentrations (>20%), poloxamers

form thermo reversible gels; they gel on heating rather than cooling.

14. Poloxamer gels are used as artificial skin, which is helpful in treating third-degree burns. The

gels are non-toxic, and prevent loss of water, heat, and electrolytes.

15. Because of poloxamer’s inverted thermo reversibility, cool solutions can be poured onto

damaged tissue, they form gels at body temperature. The gels are easily removed by rinsing with

cool water.

16. Poloxamer gels mimic mucus and are optically clear, which makes them suitable for ophthalmic

drug

17. Delivery. A poloxamer gel formulation containing pilocarpine showed improved bioavailability

over an aqueous solution of the drug.

18. Subcutaneous injection of insulin loaded poloxamer gels prolonged the hypoglycemic effect of

insulin in rats.

19. Polymers are used in making sustained release products, controlled release dosage forms and

novel drug delivery systems like liposomes, nano particles, micro capsules, trans dermal drug

delivery systems, osmotic pumps etc.

20. Polymers are used to enhance solubility and dissolution rate of drugs.

Dr. Eswar Gupta Maddi, M.Pharm., Ph.D.,Professor and Head, Dept. of Pharmaceutics, Sir C.R. Reddy College of Pharmaceutical Sciences, Eluru, West Godavari district, A.P, India 534007. Cell: +91 988 55 237 60, email: meguptas@yahoo.com, meguptas@gmail,com

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