Lecture 13 & 14 Suspension and Emulsion Theory

Describe suspensions and their desired features Identify when suspensions are preferred as a dosage form Describe advantages and disadvantages of suspensions Describe importance of physical stability of suspensions Describe sedimentation theory and factors affecting rate of sedimentation of particles Preparation of suspensions – flocculated and unflocculated suspensions What are emulsions? Different terminologies about emulsions Routes of administration of emulsions Classification of emulsions, their properties and applications Composition of emulsions, different types of emulsifying agents, Hydrophile – lipophile balance Theories of emulsification Preparation methods of emulsion Stability of emulsions Quality control tests of emulsions.

What are disperse systems?

• it is a type of preparation in which undissolved solid particles or immiscible (liquid) are distributed throughout another substance

• dispersed phase + continuous phase

What is a dispersed phase?

a. external phase

b. internal phase

c. example: water

b. internal phase

What is a dispersion/continuous medium?

a. external phase

b. internal phase

c. example: water

a. external phase

c. example: water

Which of the following dispersions are colloids?

a. coarse dispersion

b. fine dispersion

b. fine dispersion

0.1-10μM

Which of the following dispersions are seen often in pharmacy?

a. coarse dispersion

b. fine dispersion

a. coarse dispersion

• suspensions and emulsions

• have greater tendency to separate

• 10-50μM

What are suspensions?

A dispersed system in which finely divided, insoluble solid drug particles are uniformly dispersed throughout a liquid vehicle

A drug should have ___ solubility in vehicle to be dispersed

low

Which of the following is not a reason to use suspensions?

a. use when drug has high potency or small dose

b. better bioavailability

c. use when accurate dosing is critical

d. use when drug is chemically unstable in a solution

e. use when a drug tastes bad

f. patient preference

a. use when drug has high potency or small dose

c. use when accurate dosing is critical

True or false: Increasing rate of bioavailability

Solution > Suspension > Capsule > Compressed Tablet > Coated Tablet

True!

Suspensions are more bioavailable than other forms; improves chemical stability of drugs and improves controlled release of some drugs

True or false: Some advantages of suspensions are that they do not form cakes/sedimentation.

False. They do form sedimentation and forms cake which is a disadvantage.

True or false: Suspensions are thermodynamically stable.

False. They are thermodynamically unstable.

• They have the tendency to coagulate/aggregate

Which of the following are factors that lead to aggregation?

a. when particles are highly dispersed and have large surface area

b.  ↑ high surface free energy: particles want to minimize energy by sticking together

c. when particles are low in high surface free energy —> sedimentation of particles

d. Gravity leads to the sedimentation of particles —>  chance of aggregation/coagulation

a. when particles are highly dispersed and have large surface area

b.  ↑ high surface free energy: particles want to minimize energy by sticking together

d. Gravity leads to the sedimentation of particles —>  chance of aggregation/coagulation

∆G = γSL*∆A

ΔG---- change of surface free energy

ΔA---- change of total area of particles

γSL ---- Interfacial tension between solid and liquid surface

Based on this equation, how do you reduce surface free energy?

a. decrease interfacial tension

b. increase interfacial tension

c. increase surface area of particles

d. decrease surface area of particles



Which of the following are forces that bring particles together:

a. Brownian movement

b. Van der Waals forces

c. Gravity

d. Surface free energy

e. zeta potential —> Electrostatic repulsion

b. Van der Waals forces

c. Gravity

d. Surface free energy

Which of the following are forces that push particles apart:

a. Brownian movement

b. Van der Waals forces

c. Gravity

d. Surface free energy

e. zeta potential —> Electrostatic repulsion

a. Brownian movement

e. zeta potential —> Electrostatic repulsion

When ρ0 (dispersion medium) > ρs(particle density).. is it desirable or nondesirable?

nondesireable

• particles are less dense than medium

• start to float (creaming)

• example: oil droplets in water and rise to the top

When ρ_s(particle density) > ρ₀ (dispersion medium).. is it desirable or nondesirable?

desirable

• ↑ ρs(particle density) ↑ sedimentation

What are flocculated particles?

a. a loose network of particles that settle in a suspension when sedimented

b. particles that settle in a suspension that forms a cake

c. easy to re-suspend

d. hard to re-suspend

a. a loose network of particles that settle in a suspension when sedimented

c. easy to re-suspend

What are unflocculated particles?

a. a loose network of particles that settle in a suspension when sedimented

b. particles that settle in a suspension that forms a cake

c. easy to re-suspend

d. hard to re-suspend

b. particles that settle in a suspension that forms a cake

d. hard to re-suspend

What is the degree of flocculation determined by?

• Determined by forces at particle surface

• Attractive forces: van der waals

• Repulsive forces: electrostatic repulsion (Zeta potential)

What is sedimentation volume (F)?

• used to identify if suspension is flocculated or not

• Ratio of final volume of sediment to original volume

↑ F = ______ suspension while ↓ F = _______ suspension

F = 1 _____

floculated, deflocculated

If F = 1 it is deflocculation (no clear supernatant)

↑ Zeta potential means..

a. ↑ faster sedimentation

b.↓ slower settling

c.  easy to redisperse

d. deflocculation occurs (cake forms)

b.↓ slower settling

d. deflocculation occurs (cake forms)

• Zeta potential: electrical charge on particle surface; controls repulsion between particles

↓ Zeta potential means..

a. ↑ faster sedimentation

b.↓ slower settling

c.  easy to redisperse

d. deflocculation occurs (cake forms)

a. ↑ faster sedimentation

c.  easy to redisperse

If viscosity increases, then sedimentation rate _____

decreases

Viscosity is inversely proportional to sedimentary rate

𝑣 α 1/η_o

True or false: Viscosity depends on liquid content

False. It depends on solid content. Too high viscosity makes liquid hard to poor and hard to redisperse particles

What do suspending agents do to dispersion medium?

Increase viscosity to help suspend particles

examples: methylcellulose, xanthan gum, acacia

What is thixotropy?

The slow reversible conversion of gel (semisolid) to sol (liquid) with the use of force (shear stress)

↑ Thixotropy ↓ sedimentation rate

What are emulsions?

A heterogeneous system, with at least 1 immiscible liquid phase intimately dispersed throughout a 2nd phase in form of droplets or globules.

True or false: Unlike suspensions, emulsions are thermodynamically stable.

False. Both suspensions and emulsions are thermodynamically stable.

Which phase determines the physiochemical properties of the emulsion?

a. internal phase (discontinuous phase)

b. external phase (continuous phase)

b. external phase (continuous phase)

What are Oil-in-Water (o/w) emulsions?

a. have an aqueous internal phase, oleaginous external phase

b. have an oleaginous internal phase, aqueous external phase

b. have an oleaginous internal phase, aqueous external phase

What are Water-in-Oil (w/o) emulsions?

a. have an aqueous internal phase, oleaginous external phase

b. have an oleaginous internal phase, aqueous external phase

a. have an aqueous internal phase, oleaginous external phase

What is used to stabilize emulsions?

a. oleaginous agents

b. aqueous agents

c. emulsifying agents

c. emulsifying agents

Which of the following routes has W/O emulsions in addition to O/W emulsions?

a. oral

b. topical

c. ophthalmic

d. IV

b. topical

Which route of administration has this property:

Enhances bioavailability of lipophilic drugs. It also enhances dispersibility and improves solubility in an o/w

a. topical

b. iv

c. oral

c. oral

How are emulsions classified?

They are classified based on their…

• dispersed phase

• size of liquid droplets

• choice of emulsion type

In Oriented-Wedge Theory..

Emulsifying agent ___ HLB → O/W emulsion

Emulsifying agent ___ HLB → W/O emulsion

increases

decreases

The curvature the wedge formed at the interface determines the size of dispersed phase.

What are the 2 mechanisms used to prepare the methods of emulsions?

1. dispersion of 1 liquid as droplets to another liquid

• (↑ input; ↑ ΔG)

2. ↓ΔG through coalescence of formed droplets