E. Coarse Dispersion

greater than 500nm

Coarse Dispersion has particle size ___

Visible

Coarse Dispersion is (visible/not visible) under ordinary microscope

Do not pass

Coarse Dispersion (pass/do not pass) through filter paper

Do not pass

Coarse Dispersion (pass/do not pass) through semipermeable membrane

Do not diffuse

Coarse Dispersion (diffuse/do not diffuse)

Insoluble solid

What is the dispersed phase in a pharmaceutical suspension?

• Orally administered suspensions

• Externally applied suspensions

• Parenteral suspensions

3 Types of Suspensions

125 to 500 mg per 5 mL of solid material

Concentration of antibiotic suspension

High concentration

Concentration of antacid suspension and radiopaque suspension

> 20 %

Concentration of externally applied suspensions

0.5-30%

Concentration of parenteral suspensions

• Make insoluble drugs more palatable

• Provide suitable dosage form for dermatologic materials to skin and mucous membranes

• Parenteral administration of water-insoluble drugs

Advantages of Pharmaceutical Suspension

• Suspended material should NOT settle rapidly

• Sediments do NOT form a hard cake

• Readily dispersed when shaken

• Not too viscous

• For lotions: easily spread, dry quickly, have acceptable color and odor

Characteristics of an Acceptable Suspension

• Particles do not aggregate.

• They remain uniformly distributed throughout.

• Easily resuspended by moderate agitation

Physical Stability of Suspensions

• Flocculation

• Aggregation

• Caking

Interfacial Properties of Suspended Particles (3)

Flocculation

Formation of light, fluffy conglomerates or floccules that are held together by weak Van der Waals forces à flocs or floccules

Choices

• Flocculation

• Aggregation

• Caking

Aggregation

The process where particles adhere by stronger forces in compacted cake → aggregates; worse than flocculation

Choices

• Flocculation

• Aggregation

• Caking

Caking

Growth and fusing together of crystals in the precipitate to produce a solid aggregates

Choices

• Flocculation

• Aggregation

• Caking

Flocculated Suspension

Sediments are loosely pack

Choices:

• Flocculated Suspension

• Deflocculated Suspension

Flocculated Suspension

High sedimentation rate

Choices:

• Flocculated Suspension

• Deflocculated Suspension

Flocculated Suspension

High sedimentation volume

Choices:

• Flocculated Suspension

• Deflocculated Suspension

Flocculated Suspension

Easily redispersed when shaken

Choices:

• Flocculated Suspension

• Deflocculated Suspension

Flocculated Suspension

Pharmaceutically elegant suspension

Choices:

• Flocculated Suspension

• Deflocculated Suspension

Deflocculated Suspension

Sediments are tightly pack

Choices:

• Flocculated Suspension

• Deflocculated Suspension

Deflocculated Suspension

Low sedimentation rate

Choices:

• Flocculated Suspension

• Deflocculated Suspension

Deflocculated Suspension

Low sedimentation volume

Choices:

• Flocculated Suspension

• Deflocculated Suspension

Deflocculated Suspension

Difficult to redispersed when shaken; forms compact cake

Choices:

• Flocculated Suspension

• Deflocculated Suspension

Stoke’s

Velocity of sedimentation is expressed by __ Law

• Dilute Suspension → Free Settling

• >5% Suspension → Hindered Settling

Larger

(Smaller/Larger) particles settle more rapidly.

• Wetting agents

• Flocculating agents

• Dispersing agents

• Suspending agents

Components of Suspension (4)

Wetting agents

Surfactants that decrease the solid–liquid interfacial tension and contact angle between the solid particles and the liquid vehicle.

Choices:

• Wetting agents

• Flocculating agents

• Dispersing agents

• Suspending agents

Suspending agents

Retard settling and agglomeration of the particles by functioning as an energy barrier, which minimizes interparticle attraction

Choices:

• Wetting agents

• Flocculating agents

• Dispersing agents

• Suspending agents

Dispersing Agents (Deflocculants)

Do not appreciably lower the surface and interfacial tension but are used to produce deflocculated suspensions.

Choices:

• Wetting agents

• Flocculating agents

• Dispersing agents

• Suspending agents

Flocculating agents

Neutral electrolytes that are capable of reducing the zeta potential of suspended charged particles to zero

Choices:

• Wetting agents

• Flocculating agents

• Dispersing agents

• Suspending agents

Protective colloids

Do not reduce interfacial tension

Choices:

• Protective colloids

• Viscosity-builders

Protective colloids

Forms mechanical barrier around particles

Choices:

• Protective colloids

• Viscosity-builders

Protective colloids

Used in low concentration (0.1%)

Choices:

• Protective colloids

• Viscosity-builders

Viscosity-builders

Organoleptic Agents

Choices:

• Protective colloids

• Viscosity-builders

Viscosity-builders

Include the preservative, color, smell and flavor; they may materially affect the characteristics of the suspension system.

Choices:

• Protective colloids

• Viscosity-builders

• Precipitation method

• Dispersion method

• Controlled flocculation

Preparation of Suspensions (3)

Precipitation method

pH precipitation - applicable to only those drugs where solubility depends on the pH value; organic solvent precipitation

Choices:

• Precipitation method

• Dispersion method

• Controlled flocculation

Dispersion method

The vehicle must be formulated so that the solid phase is easily wetted and dispersed

Choices

• Precipitation method

• Dispersion method

• Controlled flocculation

Controlled flocculation

1) Wetting agent + Vehicle

2) + Drug → Slurry

3) Sieved

4) Agitated

5) + Flocculating agent

6) Agitated

7) Allowed to settle

8) + Adjuvants

9) Dilute to final volume

Choices

• Precipitation method

• Dispersion method

• Controlled flocculation

Emulsion

A thermodynamically unstable system consisting of at least two immiscible liquids and stabilized by emulsifying agent

• Dispersed phased (liquid) as globules

• Dispersion medium as other liquid

Surfactants

Primary emulsifying agent

Hydrophilic colloids, finely divided solids

Auxiliary emulsifying agent (2)

Oil-in-water (O/W) Emulsion

O/W or W/O:

• Dispersed Phase → Oil

• Continuous Phase → Water

• Usually for oral administration

• Emulsifiers: SLS, triethanolamine

Water-in-oil (O/W) Emulsion

O/W or W/O:

• Dispersed Phase → Water

• Continuous Phase → Oil

• Usually for external application

• Emulsifiers: sodium palmitate, sorbitan esters (Spans)

micellar emulsions

Microemulsions (a.k.a. __) - almost appear transparent or clear

• Carbohydrate Materials

• Protein Substances

• High Molecular Weight Alcohol

• Wetting Agents or Synthetic Surfactants

• Finely Divided Solids

Emulsifying Agents (5)

Carbohydrate Materials

MOA: Form hydrophilic colloids, when added to water producing o/w emulsions

Choices:

• Carbohydrate Materials

• Protein Substances

• High Molecular Weight Alcohol

• Wetting Agents or Synthetic Surfactants

• Finely Divided Solids

Carbohydrate Materials

Examples: acacia, tragacanth, agar, chondrus, pectin, xanthan, carrageenan

Choices:

• Carbohydrate Materials

• Protein Substances

• High Molecular Weight Alcohol

• Wetting Agents or Synthetic Surfactants

• Finely Divided Solids

Protein Substances

Produce o/w emulsions

Choices:

• Carbohydrate Materials

• Protein Substances

• High Molecular Weight Alcohol

• Wetting Agents or Synthetic Surfactants

• Finely Divided Solids

Protein Substances

Examples: gelatin, egg yolk, casein

Choices:

• Carbohydrate Materials

• Protein Substances

• High Molecular Weight Alcohol

• Wetting Agents or Synthetic Surfactants

• Finely Divided Solids

High Molecular Weight Alcohol

MOA: Employed primarily as thickeners and stabilizers forming o/w emulsion.

Choices:

• Carbohydrate Materials

• Protein Substances

• High Molecular Weight Alcohol

• Wetting Agents or Synthetic Surfactants

• Finely Divided Solids

High Molecular Weight Alcohol

Examples: glyceryl monostearate, stearyl alcohol, cetyl alcohol, cholesterol (the only HMW used to make w/o emulsion)

Choices:

• Carbohydrate Materials

• Protein Substances

• High Molecular Weight Alcohol

• Wetting Agents or Synthetic Surfactants

• Finely Divided Solids

Wetting Agents or Synthetic Surfactants

See D2. Principles and Application of Interfacial Phenomena

Choices:

• Carbohydrate Materials

• Protein Substances

• High Molecular Weight Alcohol

• Wetting Agents or Synthetic Surfactants

• Finely Divided Solids

Finely Divided Solids

MOA: Adsorb at the interface and form a film of particles around the globules of o/w emulsion.

Choices:

• Carbohydrate Materials

• Protein Substances

• High Molecular Weight Alcohol

• Wetting Agents or Synthetic Surfactants

• Finely Divided Solids

Finely Divided Solids

Examples: Colloidal clays (bentonite), Mg(OH)2, Al(OH)3.

Choices:

• Carbohydrate Materials

• Protein Substances

• High Molecular Weight Alcohol

• Wetting Agents or Synthetic Surfactants

• Finely Divided Solids

• Creaming

• Sedimentation

• Phase Inversion

• Flocculation/Aggregation

• Coalescence

• Breaking/Cracking

Emulsion Physical Instabilities (6)

Creaming

Upward movement of dispersed globules

Choices: 

• Creaming

• Sedimentation

• Phase Inversion

• Flocculation/Aggregation

• Coalescence

• Breaking/Cracking

Sedimentation

The downward movement of dispersed globules

Choices: 

• Creaming

• Sedimentation

• Phase Inversion

• Flocculation/Aggregation

• Coalescence

• Breaking/Cracking

Phase Inversion

An o/w changes to w/o emulsion or vice versa

Choices: 

• Creaming

• Sedimentation

• Phase Inversion

• Flocculation/Aggregation

• Coalescence

• Breaking/Cracking

Flocculation/Aggregation

The dispersed globules come together but do not fuse

Choices: 

• Creaming

• Sedimentation

• Phase Inversion

• Flocculation/Aggregation

• Coalescence

• Breaking/Cracking

Coalescence

Complete fusion of droplets

Choices: 

• Creaming

• Sedimentation

• Phase Inversion

• Flocculation/Aggregation

• Coalescence

• Breaking/Cracking

Breaking/Cracking

Complete separation of oil and water

Choices: 

• Creaming

• Sedimentation

• Phase Inversion

• Flocculation/Aggregation

• Coalescence

• Breaking/Cracking

Breaking/Cracking

Irreversible separation into a layer, as a result of coalescence of the internal phase globules.

Choices: 

• Creaming

• Sedimentation

• Phase Inversion

• Flocculation/Aggregation

• Coalescence

• Breaking/Cracking

• Surface Tension Theory

• Plastic Theory or Interfacial Film Theory

• Oriented Wedge Theory

• Viscosity Theory

Theories of Emulsification (4)

Surface Tension Theory

The use of surface-active (surfactant) or wetting agents as emulsifiers and stabilizers lowers the interfacial tension of two immiscible liquids.

Choices:

• Surface Tension Theory

• Plastic Theory or Interfacial Film Theory

• Oriented Wedge Theory

• Viscosity Theory

Plastic Theory or Interfacial Film Theory

Places the emulsifying agent at the interface between oil and water, surrounding the droplets of the internal phase as a thin layer of film adsorbed on the surface of the drops.

Choices:

• Surface Tension Theory

• Plastic Theory or Interfacial Film Theory

• Oriented Wedge Theory

• Viscosity Theory

Oriented Wedge Theory

Certain emulsifying agents orient themselves about and within a liquid in a manner reflective of their solubility in that liquid.

Choices:

• Surface Tension Theory

• Plastic Theory or Interfacial Film Theory

• Oriented Wedge Theory

• Viscosity Theory

Oriented Wedge Theory

The surfactant forms monomolecular layers around the droplets of the internal phase of the emulsion.

Choices:

• Surface Tension Theory

• Plastic Theory or Interfacial Film Theory

• Oriented Wedge Theory

• Viscosity Theory

Viscosity Theory

The viscosity of the medium aids in the emulsification by the mechanical hindrance to coalesce the globules.

Choices:

• Surface Tension Theory

• Plastic Theory or Interfacial Film Theory

• Oriented Wedge Theory

• Viscosity Theory

• Dilution Test

• Dye Solubility Test

• Electric Conductivity Test

• Fluorescence Test

Methods of determining the type of emulsion (4)

O/W

[Dilution Test] If freely mixes with water, it is ___ type.

W/O

[Dilution Test] If not diluted with water, it is ___ type.

Methylene blue and brilliant blue

Dye Solubility Test uses what water soluble dyes (2)

O/W

[Dye Solubility Test] If the dye is dissolved and uniformly diffuse

W/O

[Dye Solubility Test] If the particle of the dye lies in dumps on the surface

O/W

[Electric Conductivity Test] ___ conducts electric current.

W/O

[Electric Conductivity Test] ___ do not conduct electric current.

O/W

[Fluorescence Test] Do not produce fluorescence

W/O

[Fluorescence Test] Produce fluorescence