Interfacial Phenomena and Surfactants

If you want to entrap a drug in a micelle, you want to be above/below the CMC?

Above

At concentrations _______ the CMC, the concentration of surfactant monomer in the aqueous phase will _________ _______.

Above Remain constant

What can you do to prevent the coagulation of proteins during mixing?

Add a small amount of oil to attract hydrophobic regions and prevent accumulation of protein at the air-liquid interface

Impact of Interfaces: ___________ of surfactants onto surfaces

Adsorption

What is an example of a surface active protein we talked about in class?

Albumin

Some drugs exhibit surface active properties such as

Amitriptyline, Orphenadrine and Diphenhydramine *Be aware of interactions with other drugs and surfaces

Anionic/Cationic/Zwitterionic/Nonionic: Alkane carboxylate salts (sodium stearate)

Anionic Surfactant

Anionic/Cationic/Zwitterionic/Nonionic: Alkyl/Aryl Sulfonates (sodium dodecylbenzenesulfonate)

Anionic Surfactant

Anionic/Cationic/Zwitterionic/Nonionic: Sulfates (sodium dodecyl sulfate or sodium lauryl sulfate)

Anionic Surfactant

What happens when surfactants align at the air-liquid interface?

Association of hydrophobic groups at the air-liquid interface may result in aggregation of surfactants (tails sticking out of the water). Micelles can form if the surfactant concentration is high enough.

Anionic/Cationic/Zwitterionic/Nonionic: long chain amine salts (dodecylamine hydrochloride)

Cationic Surfactant

Anionic/Cationic/Zwitterionic/Nonionic: Quaternary Ammonium salts (CTAB)

Cationic surfactant

Hydrophobic phase is the _________ phase and water is the ________ phase

Continuous Dispersed

Factors Affecting CMC & Micellar Size: Hydrophobic Group Increasing chain length results in _____________ CMC and ___________ micelle size

Decreased Increased

Factors Affecting CMC & Micellar Size: Addition of electrolytes _________ CMC and _________ micelle size

Decreases Increases

HLB Range: 11-15

Detergents (hydrophilic)

Determining CMC: Ring attached to a wire measures the surface tension by water clinging to the wire; measuring force as you pull up

DuNouy Ring

Where are their surfactants in our bodies?

GI Tract (bile salts) Eye (surfactant protein A) Lung (pulmonary surfactant)

Entropy is _____ than the charge repulsion of micelles

GREATER (this is why micelles can form)

High HLB values suggest a compound is ________ and low HLB values suggest a compound is _________.

Hydrophilic Lipophilic

Perflubron has F where H are normally making it

Hydrophobic

What are the driving forces behind micelle formation?

Hydrophobic force and entropy

What factors affect CMC and micellar size?

Hydrophobic group Hydrophilic group Nature of Counter-ion Addition of electrolytes

Factors Affecting CMC & Micellar Size: Hydrophilic group CMC increases with ________ in chain length of polyoxyethylene chain

Increases

Factors Affecting CMC & Micellar Size: Nature of Counter Ion Micelle size increases with ____________ atomic weight of counterion

Increasing

Why should micellar drug products not be diluted prior to administration?

It could bring the concentration of the surfactant below the CMC (once below the CMC, you can't form a micelle)

Factors Affecting CMC & Micellar Size: Nature of Counter Ion The more weakly hydrated the counter ion, the ___________ the micelles.

Larger

Factors Affecting CMC & Micellar Size: Hydrophilic group Nonionic micelles have __________ CMC than their ionic counterparts

Lower -No 'electrical work' required in process of formation -May be asymmetric

Anionic/Cationic/Zwitterionic/Nonionic: Polysorbates (polyoxyethylene esters of sorbitan)

Non-ionic Surfactant

Anionic/Cationic/Zwitterionic/Nonionic: Poloxamers (Poluronics)

Non-ionic surfactants

_____ surfactants are growing in importance in pharmaceutical formulations

Nonionic (have lower CMC values)

HLB Range: 8-18

Oil in Water Emulsifiers (hydrophilic)

Micelle: Heads ________ with water ___________

Outside, Outside

Sorbitan mono-palamitate (HLB=6.7) is:

Palmitic Acid

What is an example of a low surface-tension liquid used for ventilation of lungs?

Perfluoro octyl bromide (Perflubron)

HLB Range: 1-3

Reverse micelles, most antifoaming agents (lipophilic)

Surface active proteins __________ into _____ and _________ regions and may be followed by aggregation

Separated Hydrophilic and Hydrophobic

Foam fractionation is:

Separation of surface active material using rising column of foam

Why should patients be instructed to not shake their insulin bottles?

Shaking insulin (protein) can cause air bubbles (increased surface area between the air-liquid interface) to form leading to aggregation, reducing the concentration

HLB Range: 15-18

Solubilizing Agents (hydrophilic)

Foam fractionation column with reflux:

Some of the top product is returned to the column.

Sorbitan monostearate (HLB=4.7) is sometimes called:

Span 60, Stearic Acid

Sorbitan mono-oleate (HLB=4.3) is also sometimes called:

Span 80, Oleic Acid

Hydrophilic Lipophilic Balance (HLB) is a classification system for _________ and _______ ___________ of ____________.

Surfactants Water solubility of surfactants

How would surfactants align if added to an oil?

They would form a micelle with a hydrophilic interior, sometimes called inverse micelle

T/F: Micelles can be used to increase the apparent aqueous solubility of lipophilic drugs.

True.

Polyoxyethylene (20) sorbitan monostearate (HLB=14.9) is sometimes called:

Tween 60

Polyoxyethylene (20) sorbitan monooleate (HLB=15.0) is sometimes called:

Tween 80

How can you prevent electric charges between surfactants and air-solid interfaces?

Washing with a surfactant (soap) solution (for example, inhalers or IV lines)

HLB Range: 3-6

Water in Oil Emulsifiers (lipophilic)

HLB Range: 7-10

Wetting agents (lipophilic)

Determining CMC: Dip plate into solution that measures the surface tension; measuring force as you pull plate up

Wilhelmy Plate

Can ions from preservatives affect micelle stability?

Yes

If you add more surfactant molecules, will new micelles form?

Yes, equilibrium exists between the surfactant molecules at the interface, in solution and in micelles

A double chain amphiphile (with a phosphate and amine group) is an example of a _________ surfactant.

Zwitterionic

Anionic/Cationic/Zwitterionic/Nonionic: Phosphatidyl Choline (Ledthin)

Zwitterionic Surfactant

Surface tension is between which 2 phases

air/liquid

Double chain amphiphiles have a tendency to form:

bilayer liposome

Amphipathic compounds accumulate at the ______ ______ _____ _______, results in _____ of interfacial tension

boundary between 2 phases reduction

What are the forces opposing micelle formation?

concentration gradient, Thermal (Brownian) motion, *charge repulsion between ionic polar heads

Impact of Interfaces: _________ interfacial tension between aqueous and oil phases

decrease

Adding surfactant __________ surface tension (until the CMC is reached)

decreases

Surfactants and air-solid interfaces adsorb due to:

electrostatics. The build-up of stationary electric charges on non-conducting surfaces can cause adhesion of pharmaceutical powders.

Types of Interfaces

g-g, g-l, g-s, l-l, l-s, s-s

Adding polyoxy groups ______ (increases/decreases) the HLB

greatly increases (more hydrophilic) Examples: Span 85 > Tween 80 Span 80 > Tween 20

Pluronic is hydro_____-hydro______-hydro_______-

hydrophilic - hydrophobic - hydrophilic

HLB is a measurement of

hydrophilicity to lipophilicity

Saturation will (increase/decrease) the HLB

increase

Decreasing the number of fatty acid groups __________ the HLB.

increases (more hydrophilic) Examples: Span 85 > Span 80 Tween 80 > Tween 20

Shorter carbon chains result in less ______ compounds

lipophilic

Interfacial tension is between which 2 phases

liquid/liquid

Overcoming surface tension at an air-water interface mediated by surface active proteins is crucial for:

many diverse biological processes

Genexol PM, Flucide and Basulin are all examples of

micellar drug products

Impact of Interfaces: micellar solubilization of __________-_________ drugs

poorly soluble

Beractant (Survanta), Calfactant (Infasurf), Poractant (Curosurf) and Lucinactant (Surfaxin) are examples of

pulmonary surfactant products

The critical micelle concentration is:

the surfactant concentration where micellization occurs

What is the core of a bilayer liposomes?

water (polar head groups face the core)

Phospholipids are commonly made up of:

zwitterions