L4 - Dispersed System and Interfacial Phenomenon

What are the two types of liquid dosage forms?

Monophasic and polyphasic

What are the two types of monophasic liquid dosage forms?

Aqueous solutions and non-aqueous solutions

What are the three types of polyphasic liquid dosage forms?

- Suspensions

- Colloids

- Emulsions

Describe monophasic liquid dosage forms.

Clear, homogeneous preparations with one or more drugs completely dissolved in a single phase.

Describe aqueous solution dosage forms.

Drugs dissolved in a water-based vehicle.

Describe nonaqueous solution dosage forms.

Drugs dissolved in a non-water vehicle (e.g., alcohol, glycerin, or oils).

Describe polyphasic liquid dosage forms.

Preparations containing two or more phases in which one phase is dispersed throughout another.

Describe suspension dosage forms.

Insoluble solid particles dispersed in a liquid vehicle.

Describe colloid dosage forms.

Very small particles dispersed in a liquid that remain suspended and do not settle rapidly.

Describe emulsion dosage forms.

One liquid dispersed as droplets within another immiscible liquid (e.g., oil-in-water or water-in-oil).

What is a dispersed system?

A system in which the dispersed phase (internal/discontinuous phase) is distributed throughout a dispersion medium (external/continuous phase).

What type of dispersed system is a solid dispersed in a liquid?

Suspension

What type of dispersed system is a liquid dispersed in a liquid?

Emulsion

What type of dispersed system is a solid or liquid dispersed in a gas?

Aerosol

What type of dispersed system is a gas dispersed in a liquid?

Foam

What are the three classifications of dispersed systems? What are they based on?

- Molecular dispersions

- Colloidal dispersions

- Coarse dispersions

Based on particle size.

Describe molecular dispersions.

True solutions with particle sizes <1 nm. The solute is completely dissolved and uniformly distributed.

Example: Electrolyte solutions.

Describe colloidal dispersions

Microheterogeneous systems with particle sizes 1 nm-0.5 μm. Particles remain suspended and do not settle under gravity.

Example: Milk.

Describe coarse dispersions

Heterogeneous systems with particle sizes >0.5 μm. Particles settle relatively quickly.

Example: Suspensions.

What are pharmaceutical foams?

Dispersed systems in which gas bubbles are dispersed in a liquid containing the drug.

How is gas distributed in a foam?

Gas is the dispersed phase, distributed as bubbles throughout the continuous liquid phase.

Why are surfactants needed in foams?

They reduce surface tension, allowing gas bubbles to form by reducing the air-liquid interface

What are the advantages of pharmaceutical foams?

- Non-greasy

- Easy to apply

- Good for mucosal and sensitive areas

- Rapid drug absorption

What is the interfacial phenomenon?

The behavior that occurs at the boundary (interface) between two immiscible phases.

Does the interfacial phenomenon occur in homogeneous solutions?

No

What is an interface?

The boundary between two different phases.

What is the liquid-gas interface?

The surface of a liquid exposed to air.

Example: Water surface.

What is the solid-gas interface?

The surface of a solid exposed to air.

Example: Tablet or table surface.

What is the liquid-liquid interface?

The boundary between two immiscible liquids.

Example: Oil-water interface (emulsion).

What is the liquid-solid interface?

The boundary between a solid and a liquid.

Example: Suspension.

Is a gas-gas interface possible?

Nope. Gases mix completely, so no interface exists.

Why are interfaces important in pharmaceutics?

They affect:

- Drug solubility

- Drug dispersion

- Stability of suspensions

- Stability of emulsions

Describe molecules in the bulk of a liquid.

They are surrounded by molecules of the same kind and experience equal attractive forces in all directions.

Describe molecules at the surface/interface of a liquid.

They are not completely surrounded by like molecules, so they experience unequal attractive forces with a net pull toward the bulk of the liquid.

How do surface molecules create surface tension?

The inward pull on surface molecules causes the surface to contract, producing surface tension (or interfacial tension between two liquids).

How does the ABCD wire frame demonstrate surface tension?

A soap film forms across the frame. As the film tries to shrink, it pulls the movable EK bar upward, demonstrating the force created by surface tension.

What equation describes the force produced by surface tension?

F = 2γL

What does F represent?

The force required to move the EK bar.

Units: dynes (CGS) or newtons (SI)

What does γ (gamma) represent?

Surface tension.

Units: dynes/cm or N/m

What does L represent?

The length of the movable EK bar.

Why is there a "2" in the equation F = 2γL?

Because the soap film has two surfaces (front and back), both contributing to the pulling force.

How does surface tension affect immiscible liquids?

It resists mixing by minimizing the contact between the two liquids.

What is a surface-active agent (surfactant)?

A molecule that has affinity for both immiscible phases and reduces surface/interfacial tension, allowing them to mix.

Give an example of a surface-active agent.

An amphipathic molecule (e.g., soap) in an oil-water system.

What is an amphipathic molecule?

A molecule with a hydrophilic (polar) head and a hydrophobic (nonpolar) tail.

What can happen when oil is added to the surface of water?

- Spread into a thin film

- Form a liquid lens (droplet)

- Spread as a monolayer

What determines whether a liquid will spread?

The surface tensions of the two liquids and the interfacial tension between them.

For a liquid to spread over another surface, the spreading coefficient (S) must be _____.

Positive (S > 0).

What is the equation for the spreading coefficient?

S = γs − γl − γsl

What does γs represent?

The surface tension of the substrate.

What does γl represent?

The surface tension of the spreading liquid.

What does γsl represent?

The interfacial tension between the liquid and the substrate.

What must happen before a solid can be dispersed in a liquid?

The liquid must wet the solid by replacing the air surrounding the particles.

Solid particles must be _____ before they can be dispersed in a liquid.

Wetted.

What determines whether a solid can be dispersed in a liquid?

The degree of wetting.

What determines the degree of wetting?

The contact angle (θ).

What is the contact angle?

The angle formed where a liquid drop meets a solid surface. It measures how well the liquid wets the solid.

What does a small contact angle indicate?

Good wetting (the liquid spreads).

What does a large contact angle indicate?

Poor wetting (the liquid beads up).

What contact angle represents complete wetting?

θ = 0°

What contact angle represents no wetting?

θ = 180°

What contact angles represent partial wetting?

Surface tension of the spreading liquid0° < θ < 180°

What contact angle is considered highly wettable?

Less than 20°.

Above what contact angle is a surface generally considered nonwettable?

Greater than 90°.

What are wetting agents?

Surfactants that lower the contact angle, allowing liquids to spread more easily over solids.

How do surfactants improve wetting?

They lower surface tension and interfacial tension, reducing the contact angle.

Do hydrophilic materials have high or low contact angles?

Low contact angle → Good wetting.

Do hydrophobic materials have high or low contact angles?

High contact angle → Poor wetting.

Describe the distribution of charge at an interface.

An interface has an uneven distribution of charge, with opposite charges on each side, while the overall system remains electrically neutral.

What is the Stern layer?

The tightly bound layer of counterions directly attached to the charged particle surface.

What is a diffuse layer (Gouy-Chapman)?

A loosely bound layer of counterions surrounding the Stern layer that can move freely.

What is the electrical double layer?

The combination of the Stern layer and the diffuse layer surrounding a charged particle.

How do the Stern and diffuse layers differ?

Stern layer: Tightly attached to the particle.

Diffuse layer: Loosely associated and mobile.

Where is charge density greatest?

At the particle surface, then it gradually decreases with distance.

What happens when two particles with electrical double layers approach each other?

Their double layers create electrostatic repulsion, helping keep the particles apart.

What is the zeta potential?

A measure of the electrical potential at the edge of the double layer that reflects the strength of repulsion between particles.

What does a high zeta potential indicate?

Strong repulsion and a more stable suspension.

What does a low zeta potential indicate?

Weak repulsion, allowing particles to stick together and aggregate.

Reminder: What are surface-active agents (surfactants)?

Amphipathic molecules that accumulate at interfaces and reduce surface/interfacial tension, allowing immiscible liquids to mix.

How are surfactants classified?

By the charge of their polar (hydrophilic) head group.

What are anionic surfactants?

Surfactants with a negatively charged head group.

Examples: Sulfates, sodium lauryl sulfate (SLS).

What are cationic surfactants?

Surfactants with a positively charged head group.

Examples: Quaternary ammonium compounds, benzalkonium chloride.

What are nonionic surfactants?

Surfactants with an uncharged polar head group.

Examples: Tween® and Span®.

What are zwitterionic surfactants?

Surfactants with both positive and negative charges, but an overall net charge of zero. Their charge behavior can change with pH.

What determines whether an amphipathic molecule is more hydrophilic or hydrophobic?

The balance of its polar and nonpolar groups.

What makes an amphipathic molecule more hydrophobic?

A longer hydrocarbon (alkyl) chain, making it more lipophilic and less water-soluble.

What makes an amphipathic molecule more hydrophilic?

A shorter hydrocarbon chain and/or larger polar region, making it more water-soluble.

What is the Hydrophilic-Lipophilic Balance (HLB)?

A numerical scale that indicates whether a surfactant is more hydrophilic or lipophilic.

What does a high HLB value indicate?

A more hydrophilic surfactant that favors oil-in-water (o/w) emulsions.

What does a low HLB value indicate?

A more lipophilic (hydrophobic) surfactant that favors water-in-oil (w/o) emulsions.

How can drugs or preservatives interact with their containers?

They can be adsorbed onto the container surface, reducing their amount in solution.

What happens if a drug is adsorbed onto the container?

The drug concentration in solution decreases.

What happens if a preservative is adsorbed onto the container?

The preservative concentration decreases, leaving the product less protected against microbial growth.

What are three ways surfactants adsorb onto solid surfaces?

Ion exchange - replaces similarly charged ions.

Ion pairing - binds to oppositely charged sites.

Hydrogen bonding - forms hydrogen bonds with the surface.

How can ion exchange cause surfactant adsorption?

The surfactant replaces ions of the same charge that are already attached to the solid surface.

How can ion pairing cause surfactant adsorption?

The surfactant binds to oppositely charged sites on the solid surface.

How can hydrogen bonding cause surfactant adsorption?

The surfactant forms hydrogen bonds with the solid surface.