Physical Pharmacy 2

1K A U S A R A H M A DK U L L I Y Y A H O F P H A R M A C Y , I I U M

H T T P : / / S T A F F . I I U . E D U . M Y / A K A U S A R

POLYMER SOLUTIONS

CONTENTS

• Molecular characteristics• Polymer assemblies• Polymer dissolution • Polymer swelling• Viscosity of polymer solutions• Solubility factors• Gel• Interactions in polymer solutions• Solubility parameter

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MOLECULAR CHARACTERISTICS

• Polymers are dispersed as isolated molecules in very

dilute solutions

• molecular characteristics necessary for understanding

polymer properties can be determined:

• chain length, conformation, and flexibilityhttp://www.chem.sci.osaka-u.ac.jp/graduate/mms/English_version/Norisuye_lab.html

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XANTHANT. SATO ET AL. MACROMOLECULES, 17, 2696 (1984)

• A polyelectrolyte polysaccharide which is produced by a parasitic bacteria on cabbage and used as a food gum. This polymer takes double-stranded helix structure in aqueous solutions with salts.

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POLYMER ASSEMBLIES

In solution, polymer chains exist in various states e.g.

1. uniformly molecularly dispersed state (dilute)

2. aggregating or micellar state

• a number of polymer chains are assembled together

3. gel state

• polymer chains form a network though the system

4. liquid crystalline state

• polymer chains align toward a certain direction

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FACTORS AFFECTING POLYMER ASSEMBLIES

• chemical structure

• chain conformation

• intermolecular interaction of polymers

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INTERPOLYMER INTERACTION

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CONCENTRATED SOLUTION

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LIQUID CRYSTAL

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Helix

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ASSOCIATION MICELLE, GEL

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AMPHIPHILIC POLYMERS

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POLYMER DISSOLUTION HTTP://WWW.PSRC.USM.EDU/MACROG/PROPERTY/SOLPOL/PS1.HTM

• the dissolution of a polymer is a slow process

• due to size, structure/coiled shape, MW & the attraction forces between them, polymer molecules become dissolved quite slowly than low molecular weight molecules.

• when a low MW solute such as sucrose is added to water, the dissolution process takes place almost immediately.

• The sugar molecules leave the crystal lattice progressively, disperse in water, and form a solution.

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POLYMER DISSOLUTION PROCESS

• Billmeyer Jr. (1975) points out that there are two stages involved in this process:

1. polymer swelling

2. dissolution

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POLYMER SWELLING

When a polymer is added to a given solvent, attraction as well as dispersion forces begin acting between its segments, according to their polarity, chemical characteristics, and solubility parameter.

If the polymer-solvent interactions >> polymer-polymer attraction forces, the chain segment start to absorb solvent molecules, increasing the volume of the polymer matrix, and loosening out from their coiled shape

the segments are now "solvated" instead of "aggregated", as they were in the solid state. Thus swollen.

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DISSOLUTION PROCESS FOR POLYMER MOLECULES

VISCOSITY OF POLYMER SOLUTIONS

For small molecular size, the solute does not swell when dissolving. Since molecular mobility is not restricted, and therefore intermolecular friction does not increase drastically, the viscosity of the solvent and the solution are similar. In the dissolution process of polymers, such big molecules swell appreciably, restricting their mobility, and consequently the intermolecular friction increases. The solution in these cases, becomes highly viscous. THUS VISCOSITY MODIFIER!

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SOLUBILITY FACTORS

Rate of dissolutio

n decreases

Increasing molecular

weight

Increasing degree of crystallinit

y Increasing number of crosslinkin

g

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GEL

A three-dimensional crosslinked network

• Drastic increase in viscosity• Rubber-like, elastic• At high concentration will yield a stress point

Defined by a critical concentration or temperature and depends on• Structure of polymer• Polymer-solvent interaction• Molecular weight • Chain flexibility

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TYPE 1 GEL

Irreversible formation of gel as a result of network formed by covalent crosslinking

Used in drug delivery

• Poly(glycol methacrylate) implant• Surgical suture with gel coating• Softlens• Eye medication via viscosity control

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TYPE 2 GEL

Most common in pharmaceutical application

Heat-reversible gel held by intermolecular bonds, e.g. hydrogen bond in aqueous medium

10% PVA aqueous solution formed a gel at 14oC. When applied to skin, it dries up and leave a layer of the intended drug

Gel point can be altered

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HETEROGELS

• A copolymer A-B may exhibit different structure • when immersed in different solvents

• depending of the swellability of the composites A and B towards the solvent

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INTERACTIONS IN POLYMER SOLUTIONS

Formation of polymer complexes• Some biological macromolecules reactions are important esp

on effects of drugs, viscosityBinding of ions to macromolecules• E.g. calcium ions to polysaccharides

Adsorption of macromolecules• Stabilisers for suspension and emulsion

Interaction with solvents• Swelling and drug release

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INTERACTION WITH SOLVENTS

Swelling and drug release: Sw = vd(t)/D

Sw - swelling interface numberv - the viscosity of solvent, d(t) - thickness of polymer D - diffusion coefficient of drug in polymer

Swelling is a function of temperature Application in disposable towels and nappies

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SOLUBILITY PARAMETER

• unit (cal/cm3)1/2or SI unit:(cal/cm3)1/2 = (4.187 J/10-6m3)1/2 = 2.046 x 103

(J/m3)1/2 = 2.046 MPa1/2 • solubility parameters useful when studying how

capable is a polymer to being dissolved in a given solvent.

• above equation is valid only for solutions where strong polymer-solvent interactions do not take place.

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SOLUBILITY PARAMETERS FOR SOLVENTS & POLYMERS FROM "POLYMER HANDBOOK" / J. BRANDRUP AND E.H. IMMERGUT, EDS., 3RD ED., WILEY-

INTERSCIENCE, NEW YORK, 1989)

Solvent ds (MPa1/2) Polymer dp (MPa1/2)

Carbon Tetrachloride

17.6 Polyethylene 15.8-18.0

n-Hexane 14.9 Polymethylmethacrylate

18.4-26.3

Toluene 18.2 Nylon 6.6 27.8

Water 47.9 Polyvinyl alcohol 25.8

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REFERENCES

Aulton, M. E. (1988). Pharmaceutics: The Science of dosage form design. London: Churchill Livingstone.

Chasin, M & Langer, R (1990). Biodegradable polymers as drug delivery systems. New York: Marcel Dekker.

Florence, A. T. & Attwood, D. (1988). Physicochemical Principles of Pharmacy

(2nd ed.). London: Chapman & HallMartin, A. N. (1993). Physical Pharmacy: Physical chemistry principles in

Pharmaceutical Science (4th ed.). Philadelphia: Lea & Febiger.Vyas, S. P & Khar, R. K. (2002). Targeted and controlled drug delivery. New

Delhi: CBS.Wise, D. L. (2000). Handbook of Pharmaceutical Controlled Release Technology.

New York: Marcel Dekker.

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