Physical Pharmacy 2

1K A U S A R A H M A D

K U L L I Y Y A H O F P H A R M A C Y , I I U MH T T P : / / S T A F F . I I U . E D U . M Y / A K A U S A R

INTRODUCTION TO POLYMERS

CONTENTS

Polymers in drug delivery• Copolymer• Polysaccharides

Properties of polymers• Crosslink density• Molecular weight

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POLYMERS IN DRUG DELIVERY

use in drug delivery due to

Surface activity efficient stabilisers for colloidal drug delivery system

Gel forming capacity

rheological control

Formation of self-assembly structure

analogous to simple surfactants: solubilisation of sparingly-soluble drugs

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POLYMERS IN DELIVERY SYSTEMS:EXAMPLES

Polyurethane• elasticity• catheter

Polysiloxane/silicone• inert• implants

Polymethyl methacrylate• physical strength & transparency

Polyvinylalcohol• hydrophilicity & strength

Polyethylene• toughness & lack of swelling

Polyvinyl pyrrolidone• suspension capabilities

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BLOCK COPOLYMERS

• Consisting of block of two or more polymers

• Example is poly(ethylene oxide)-poly(propylene oxide) block copolymers:

H-OCH2CH2)a(OCH2CHCH3)b(OCH2CH2)cOH

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ADVANTAGE OF BLOCK COPOLYMERS

• degradation rate of polymers can be

controlled.

• can obtain controlled drug release

• protect compound from harsh environment • e.g. in stomach – in particular polymers containing

poly(lactic) acid or poly(glycolic) acid

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EXAMPLE OF BLOCK COPOLYMERS

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Poly(lactic) acid

Poly(glycolic) acid

POLYSACCHARIDES

• Mainly due to formation of gels in aqueous solutions

• Examples: • carrageenans• alginates• starch

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CHEMICAL STRUCTURE OF SOME POLYSACCHARIDES USED IN DRUG DELIVERY

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PROPERTIES OF POLYMERS

• High molecular weight

• Repeating units

• Exist as linear or branched

• Can be crosslinked

• Properties depend on the polymerisation of the

monomers

• Can be divided into homopolymers or copolymers

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TYPES OF COPOLYMERS

These can be further divided into:

1. Alternating

2. Block

3. Graft or branched

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NATURAL POLYMERS

• Chemical modification can be carried out

to change the properties

• Example: Crosslinking

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RIGIDITY

In decreasing order:

• Plastics• Rubbers• Elastomers

Can be related to the glass transition temperature

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STRUCTURE OF POLYMER

Linear Branched Crosslinked

Thermoset polymer

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CROSSLINK DENSITY

The extent of crosslinking in a polymer is expressed as the crosslink density

As number of crosslinks increases, the glass transition temperature increases.

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From: Florence & Attwood

MOLECULAR WEIGHT/TEMPERATURE & POLYMER PROPERTIES

MOLECULAR WEIGHT

Both natural and synthetic polymers do not have specific molecular weight

Molecular weight is normally expressed as an average

The range of molecular weight is described by the POLYDISPERSITY

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MOLECULAR WEIGHT DETERMINATION

Methods that can be used are:-

1. Chemical analysis

2. Osmotic pressure

3. Light scattering measurement

4. Gel permeation chromatography

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AVERAGE MW

• The averages can be in terms of:-• Number• Weight• Viscosity• Z (sedimentation)

• The above depends on the type of analytical method employed

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NUMBER AVERAGE MW

i

iin

n

MnM

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Determined by:1. Osmometry2. End-group titration 3. Colligative properties

WEIGHT AVERAGE MW

ii

iiw

Mn

MnM

2

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• Determined from1. Light scattering 2. Small Angle Neutron Scattering

(SANS) 3. Sedimentation velocity [Hiementz]

• Bias towards larger molecules

VISCOSITY AVERAGE MW

Determined by intrinsic viscosity

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a

ii

aii

vMn

MnM

/11

MARK-HOUWINK EQUATION

h = KMva

• ‘K’ and ‘a’ are the Mark-Houwink parameters and depend on polymer-solvent characteristics.

• rigid rods, a=2. • hard sphere, a=0. • good solvent, a=0.8

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Z-AVERAGE MW

Determined by sedimentation equilibrium

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2

3

ii

iiz

Mn

MnM

POLYDISPERSITY

• The ratio of Mw/Mn is the degree of

polydispersity

Mw/Mn > 1

• The smaller the ratio, the narrower is the

distribution in molecular weight of the

polymer

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MOLECULAR WEIGHT DISTRIBUTION

REFERENCES

Aulton, M. E. (1988). Pharmaceutics: The Science of

dosage form design. London: Churchill Livingstone.

Wise, D. L. (2000). Handbook of Pharmaceutical Controlled

Release Technology. New York: Marcel Dekker.

Chasin, M & Langer, R (1990). Biodegradable polymers as

drug delivery systems. New York: Marcel Dekker.

Vyas, S. P & Khar, R. K. (2002). Targeted and controlled

drug delivery. New Delhi: CBS.

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