Polymer Chemistry Quiz

Introduction to Pharmaceutical Polymers

• Polymers are made of repeating units.
• Macromolecule refers to any large molecule, not necessarily made of repeating units.
• Polymers are a subset of macromolecules.

Monomers, Dimers, Trimers, Oligomers, and Polymers

• A monomer is a small molecule combining with others to form a polymer.
• If two, three, four, or five monomers are attached, the product is a dimer, trimer, tetramer, or pentamer, respectively.
• An oligomer contains 30 to 100 monomeric units.
• Products containing over 200 monomers are polymers.
• Polymers cannot exist as gases due to high molecular weight; they exist as liquids or solids.

Polymer Synthesis

• Monomers interact to form polymers.
• Polymerization mechanism is dependent on the monomer's structure.

Addition Polymerization

• Unsaturated monomers with double or pi bonds require low energy to break.
• Polymerization begins at the site of the double bond, with the addition of a free radical.
• Typically used for monomers with double bonds (ethylene-based) or sterically strained cyclic monomers.
• Fast, high MW chains are formed at the beginning of the reaction (e.g., Styrene and acrylic acid derivatives).
• Polymerization involves three steps:
  • Initiation: Radical is transferred to monomer, forming a monomer radical.
  • Propagation: Monomer radical attacks another monomer, creating macroradicals (repeating units).
  • Termination: Macroradicals react with each other or an inert compound, stopping the chain reaction.

Condensation Polymerization

• Monomers without double bonds but with reactive functional groups (e.g., hydroxyl, carboxyl, or amines) interact via condensation.
• Slower, high MW polymer is formed near the end of polymerization when most of the monomer is depleted.
• Examples include nylon and polyester.
• A monomer containing reactive hydrogen from an amine residue can react with another monomer containing a reactive hydroxyl group to form an amide group and water.

Polymer Synthesis Techniques

• Bulk polymerization
• Solution polymerization
• Suspension and inverse suspension polymerization
• Emulsion and inverse emulsion polymerization (dispersed systems)

Bulk Polymerization

• Advantages: simplest technique, highest polymer purity, high yield, and easy polymer recovery.
• Requirements: only a monomer, a monomer-soluble initiator, and sometimes a chain-transfer agent to control the molecular weight.
• Limitations: removing residual monomer, heat dissipation, especially in free-radical polymerization.
• If the monomer is water-soluble, a linear water-soluble polymer is prepared.
• If the monomer is oil-soluble, a linear oil-soluble polymer is prepared.

Solution Polymerization

• To solve the problem of exothermic heat in bulk polymerization, polymerization is conducted in solution.
• Solvent (diluent) molecules reside between monomer molecules, reducing interactions between neighboring monomers.
• Less heat is generated in a given time period.
• Solvent should dissolve monomer and initiator, and have suitable melting and boiling points for the reaction conditions and solvent removal.
• Disadvantages include relatively low yield and the need for a solvent removal step.

Dispersion Polymerization

• Two incompatible phases (water and oil) are dispersed into each other.
• The active material (monomer) can be water-soluble or oil-soluble.
• The monomer (dispersed phase) is dispersed into the continuous phase using a surface-active agent (surfactant).
• Surfactant should be soluble in the continuous phase.
• Factors controlling the dispersion system: surfactant concentration and surface tension.
• Emulsion systems using water as a continuous phase are known as latex.

Copolymers and Polymer Blends

• Polymer systems can be physically blended or chemically reacted if one system cannot meet the needs of the application.
• Copolymerization: polymerization reaction involving more than one monomer type.
• Homopolymer: polymerization process using one monomer type (e.g., polyethylene).
• Monomer sequence can range from random to perfectly alternating; sequence determined by relative reactivities of monomers.
• Examples: Eudragit polymers

Copolymers (Continued)

• If two monomers have similar reactivities, the result is a random copolymer.
• If one monomer is preferentially added to another, the result is an alternate copolymer.
• When monomers preferentially add to themselves, a block copolymer is formed.
• A monomer and a polymer are generally used to make graft copolymers.
• Pluronic surfactants (EO-PO-EO terpolymers) are composed of block units of ethylene oxide and propylene oxides.

Copolymer Examples

• Illustrative diagrams showing different copolymer structures (homopolymer, random copolymer, alternate copolymer, block copolymer, and graft copolymer).

Polymer Blends

• Polymer properties can be changed by mixing or blending two different polymers in a molten or solution state.
• Examples include making thermoplastic polymers rigid with the addition of flexible polymers like rubber.

Interpenetrating Polymer Networks (IPNs)

• Semi-IPNs are prepared by dissolving one polymer into a solution of another monomer.
• An initiator and cross-linker are added, and the monomer polymerizes and becomes cross-linked in the presence of the dissolved polymer.
• The result is a structure where one cross-linked polymer interpenetrates the non-cross-linked polymer.
• In complete IPNs, two different monomers and their respective cross-linkers polymerize and cross-link simultaneously.

Polymer Topology

• Topology of a polymer describes its structure as linear, branched, or cross-linked.
• Topology affects polymer properties.
• Linear polymers have non-covalent (weak) intermolecular forces holding chains together.
• Linear polymers show dual behavior:
  • Linear chains move freely, resulting in low melting temperature.
  • Linear chains have a higher chance of approaching each other, increasing crystallinity and melting temperature.

Polymer Topology (Continued)

• Branched polymers have chains moving with difficulty due to steric hindrance; weaker intermolecular forces help them move freely.
• In cross-linked polymers, chains are chemically linked, restricted from movement depending on cross-linking level, resulting in very rigid structures.

Polymer Isomerism

• Structural isomerism: occurs when there are unsaturated sites along a polymer chain, leading to cis and trans isomers, differing in glass transition and melting temperatures.
• Sequence isomerism: monomers with pendant groups can attach in head-to-tail, head-to-head, or tail-to-tail conformation.
• Stereoisomerism: applies to polymers with chiral centers, presenting three different configurations (isotactic, syndiotactic, atactic) based on the position of pendant groups.

Thermoplastics

• Polymers with linear or branched structures.
• Can be reversibly refabricated and reshaped with heat (undergo melting).
• Are originally solids that can flow upon heat application.
• The process of melting and solidifying can be repeated indefinitely (e.g., polystyrene, polyethylene, polypropylene, PVC).

Thermosets

• Formed from cross-linked polymers (combination of a cross-linker and heat or combination of heat and internal functional group reaction).
• Resist thermal softening and cannot be reshaped.
• Their flow behavior is temperature-independent.
• No reversible melting and solidifying (e.g., epoxy, fiberglass).

Crystalline and Amorphous Polymers

• Polymers have varying thermal, physical, and mechanical properties depending on structure, molecular weight, linearity, and interactions.
• In linear polymers, chains pack regularly, creating crystalline lattice and exhibiting sharp melting temperatures.
• Irregular polymer structures lead to glassy or amorphous regions.
• Amorphous polymers soften over a wide temperature range.

Thermal Transitions

• When a crystal melts, polymer volume significantly increases due to the liquid state.
• Melting temperature (Tm) represents a first-order thermal transition.
• Amorphous polymers undergo broad, continuous changes (glass transition, Tg) over a wide temperature range, representing a second-order thermal transition.
• Differential scanning calorimetry (DSC) can detect Tm and Tg as endothermic peaks and baseline shifts, respectively.

Glass Transition Temperature (Tg)

• Tg is not an absolute property but is influenced by factors, affecting polymer chain movement.
• Below Tg, amorphous polymers are hard, stiff, and glassy.
• Above Tg, polymers are rubbery and flow more easily.
• Tg value in linear organic polymers ranges from about -100°C to above 300°C.

Glass Transition Temperature (Tg) (Continued)

• Tg is an important factor for solid dosage forms, such that a chewable dosage form needs to be soft and flexible at mouth temperature (37°C).
• This implies that polymers used for chewable matrices should have Tg close to 37°C.
• Example: Nicotine gum (Nicorette® gum)

Glass Transition Temperature (Tg) (Continued)

• Segmental motion in polymers is facilitated by free volume between polymer chains.
• Free volume increases with chain length and affects segmental movement and thus Tg.
• Longer end-to-end distances obtained if chains are longer and have more interactions with the solvent.
• Hydrophilic polymers are better dissolved in water; lipophilic polymers in organic solvents.

Factors Affecting Tg

• Chain length: Shorter chains, lower molecular weights result in less restriction and lower Tg.
• Side groups: Bulky side groups hinder motion, increasing Tg. Polar groups lead to stronger intermolecular forces, again increasing Tg.
• Chain Flexibility: more flexibility lowers Tg.
• Cross-linking: cross-linking limits chain movement, increasing Tg; highly cross-linked polymers have very high Tg values.
• Plasticizers: plasticizer molecules increase polymer chain entropy and mobility, lowering Tg.

Molecular Weight of Polymers

• Typical polymer batches have chains of different lengths and molecular weight distributions.
• Narrow molecular weight distributions are desired for mechanically strong polymers.
• Polymer molecular weight is expressed as an average due to chain variations.
• Number-average MW (Mn), weight-average MW (Mw), and viscosity-average MW are common methods for polymer weight expression.
• Polydispersity (PD): the ratio Mw/Mn; this value indicates how homogeneous/heterogeneous the polymer is with regard to molecular weight.

Mechanical Properties

• Polymer mechanical properties depend on structure, molecular weight, and intermolecular forces.
• Important properties include tensile strength, compressive strength, flexural strength, impact strength, and fatigue.
• Flexible polymers perform better under stretching, while rigid ones are better for compression.
• Some polymers do not have a breaking point; they deform and yield before breaking apart.
• Toughness relates to the energy needed to break the polymer (area under the stress-strain curve).

Viscoelastic Properties

• Polymers are viscoelastic, neither pure solids nor pure fluids; they store and dissipate energy (elastic and viscous behaviors).
• Examples include poly(vinyl chloride) (PVC), which behaves like a solid at temperatures below Tg (100°C) and like a fluid above.
• Viscoelasticity can be measured through creep tests (applied stress and deformation monitored over time) and stress relaxation tests (deformed polymer and observed stress decrease over time).

Varieties of Polymers-Rubbers

• Silicone rubber is a very inert rubber with low affinity to other materials.
• It is a good candidate for implants.
• Rubbers tend to be weak in their raw forms but can be crosslinked and cured under high pressure and temperature to improve strength.
• Tg of rubbery polymers (elastomers) are usually below room temperature.

Plastics

• Plastics generally have a Tg above room temperature.
• Plastics are manufactured through injection molding, extrusion, and thermoforming, requiring a molten state.

Plastics (Continued)

• Polymers like polyethylene, polypropylene, and polystyrene have only carbon in their backbone.
• Engineering plastics (polyesters, polyamides, and polyacetals) used in engineering applications resist impact, weather, and solvents and have high intermolecular forces, giving them high melting points.

Fibers

• Polymers used for fibers must have a crystalline structure with a sharp melting point—this allows them to be melt-spinnable.
• Examples of fiber-forming materials include cellulose acetate, rayon, polypropylene, nylon, polyesters, polyamides, and polyacrylonitrile.

Adhesives

• Polymers for adhesives need adhesive properties balancing cohesive forces (interaction within the material).
• Strength of adhesive forces (interaction with the second material) and cohesive forces (interaction within itself) increases with molecular weight due to increased interactions.
• Polar polymers adhere to polar surfaces (like dissolves like).

Coatings

• Coatings protect underlying materials from various environments (air, oxygen, water, stomach fluid, solvents).
• Examples include poly(vinyl acetate), acrylates, and ethyl cellulose.

Polymers as Rheology Modifiers

• Polymer chains coil when resting and extend when loaded.
• Increased solution viscosity is often desired; adding polymers to increase end-to-end chain distance under load is a common strategy.
• Loading of a polymer in dissolution/swelling processes depends on polymer interactions with solvents.
• Longer chains will interact more, creating greater viscosities.
• Hydrophilic polymers are excellent solvent candidates for water.

Hydrogels

• Hydrogels consist of hydrophilic polymers able to swell in water, holding large amounts of water.
• Cross-links (chemical bonds, cohesion forces) are important for maintaining hydrogel structure.
• Hydrogels behave like elastic solids, able to return to their original shapes after loading.
• Nonionic hydrogels rely on polymer-solvent interactions for swelling; ionic hydrogels rely on osmotic and electrostatic forces.

Chemical Gels

• Chemical gels are cross-linked by covalent bonds.
• Unlike physical gels, chemical gels do not readily dissolve in water or solvents unless the covalent cross-links are broken.
• Cross-linking via double bonds may be energetically favored compared to reactions between functional groups.

Physical Gels (Continued)

• Hydrogen bonding, hydrophobic interactions, and complexation are important methods in creating physical gels.
• Hydrogen bonding is important for some polymers (e.g., polyvinyl alcohol).
• Hydrophobic interactions play a role in thermoresponsive hydrogels (e.g., some cellulose derivatives).
• Complexation, e.g., alginate with chitosan, is also used to create gels, and the complex solubility is pH-dependent.