Dispersed Systems-Hindle

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A_______is insoluble solid particles dispersed in a liquid medium.

Suspension

___________ is liquid droplets diapered in a liquid medium. The dispersed liquid is neither soluble nor miscible with the dispersion medium.

Emulsion

A ______________ is a type of mixture where one substance is dispersed evenly throughout another. The dispersed phase is usually in the size range of 1nm to 0.5µm.

Colloidal Dispersion - A colloid

The degree of subdivision and the forces associated with large surface area distinguish the _________from the other dispersions.

Colloidal Dispersion

True or false: There is a reluctance to develop disperse systems when an alternative system is available?

True

The most common dispersion medium is _______?

Water

A _______ system is a heterogeneous system in which one phase is dispersed (hopefully with some degree of uniformity) in a second phase.

dispersed system

True or false: The disperse phase is often relatively thermodynamically stable?

False---they are often thermodynamically unstable.

The disperse phase in the systems mostly commonly encountered can be described as __________ or ____________.

lyophobic (solvent hating) or hydrophobic (water hating)

True or false: An example of a lyophobic dispersion is a water soluble drug in a suspension?

False-----for a lyophobic dispersion, it would be a water INSOLUBLE drug in a suspension

True or false: An example of a lyophobic dispersion is an oil phase in an oil in water emulsion?

True

Disperse phase systems can also be classified by particle size.

Suspension and emulsion systems are considered course dispersions. The disperse phase has particle sizes of __________?

10-50μm

Colloidal dispersion or Microemulsion have disperse phase particle sizes of __________?

1nm to 0.5μm

What types of drugs are particularly suitable for formulation as disperse systems?
1.
2.
3.

1. Oils/liquids which are not suitable for formulation as solid dosage forms or in aqueous solutions

2. Rx's that are insoluble in the aqueous phase

3. Rx's that are unstable in aqueous phase

Although difficult to formulate, due to their inherent thermodynamic instability, dispersed systems are advantageous in a number of situations:
1.
2.
3.
4.
5.
6.

1. To mask the taste

2. To improve chemical stability

3. Alter the onset of action

4. For improved compliance for pediatrics and the elderly

5. Flexibility of dosage range

6. Allows higher doses compared to solution formulations which are limited by solubility

What are the three disadvantages of a dispersed system formulation?

1. Poor physical stability
-formulations are thermodynamically unstable

2. Poor dosing uniformity characteristics
- can vary over life of product, repeated dispersion may be necessary

3. Microbial contamination
- more difficult to incorporate the appropriate preservatives

True or false: Surface tension can be defined for a liquid-air interface?

true

True or false: Surface tension can be defined for a liquid-liquid interface?

false

________ can be defined as the force needed to oppose the pull of the molecules in the surface to minimize the size of that surface (break the surface or the surface tension).

Surface tension

The surface tension of water is 72 dynes/cm

_________is the work done to increase the surface by one unit of area.

Surface Free Energy

the surface free energy of water is 72 ergs /cm2

True or false: Surface tension of liquid increase w/ increasing temperature due to lowering of the intermolecular cohesive forces as the temperature increases.?

False---Surface tension decreases with increasing temperatures

Interfacial tension is somewhat similar to surface tension in that cohesive forces are also involved. However the main forces involved in interfacial tension are __________ between the dissimilar materials.

adhesive forces

The interfacial tension reflects the imbalance of ______at the interface.

forces

The interfacial tension value is generally between surface tension values of the____________?

two immiscible liquids

True or false: spreading is generally not a liquid on liquid term?

False---it is a liquid on liquid term

True or false: When a substance is place on a surface (e.g. water), it will spread as a film if the force of adhesion between the substance and water is less than the cohesive forces of the substance itself

False--it will spread if the adhesion b/w the substance and water is GREATER than the cohesive forces of the substance itself.

__________values for the spreading coefficient (S = Wa - Wc) indicate that the substance will spread on the surface.

positive

_________is the tern that is applied to pure liquids and defines the cohesive forces between similar molecules

Work of Cohesion

___________is the term applied to two dissimilar materials and defines the adhesive forces between them

Work of Adhesion

_____ is the contact between a liquid and a solid surface, resulting from INTERMOLECULAR interactions when the two are brought together.

Wetting

A ________ lowers the advancing contact angle and aids in displacing an air phase at the surface and replacing it with a liquid phase

wetting agent

True or false: Wetting is generally considered a liquid on solid term?

True

True of false: A wetting agent that increases the contact angle is desired?

False---a wetting agent that decreases the contact agent is desired.

__________ are substances that have a tendency concentrate at the surface or interface. They can have a number of effects on the nature of the surface, most significantly lowering its surface tension.

surfactants

Surfactants can have a number of effects on the nature of the surface, most significantly lowering its ______________

surface tension.

Surfactants usually possess a _______ and a ________region - They are said to be __________.

hydrophilic and a hydrophobic region

amphiphilic

The the hydrophilic region of a surfactant is the _______?

The lipophilic region is the ________?

-head

-tail

The _______ value for a given surfactant is the relative degree to which the surfactant is lipophilic or hydrophilic.

HLB

The lower the HLB value the more_____.

The higher the HLB value the more_____.

lipophilic

hydrophilic

True or false: To get a more desired HLB value, one can blend surfactants with different HLB values?

True----HLB values are additive

A _________ is an aggregation of surfactant molecules which occurs in the liquid bulk when the surfactant concentration reaches its (CMC).

micelle

CMC==critical micelle concentration

_______CMC, only monomers present.

Below

________CMC, there are micelles in equilibrium with monomers.

above

Normal micelles usually have a _____ and ____ and are capable of solubilizing water insoluble drug in an aqueous solution.

hydrophilic shell and a lipophilic core

Reverse micelles usually have a ________ and ______ and are capable of solubilizing polar drugs in a non-aqueous environment.

lipophilic shell and a hydrophilic core

________ refers to a two-phase system consisting of a finely divided solid drug dispersed in a liquid (the dispersing medium).

Suspension

True or false: The particles in a suspension are large enough to sediment under the influence of gravity?

True

True or false: Suspensions contain one or more soluble drugs in a vehicle?

False---suspensions contain one or more INSOLUBLE drugs in a vehicle.

True or false:The particle size of the drug in suspension should change during standing.

False: The particle size should remain FAIRLY CONSTANT constant during standing.

True or false: A suspension should pour readily and evenly to ensure reproducible dosing?

true

Why formulate as a suspension?
1. __________________________________
2. __________________________________
3. __________________________________
4. __________________________________
5. __________________________________

1. Drug insoluble in aqueous vehicle

2. Allows higher dose than solution formulation

3. Drug is unstable when dissolved in solution

4. Liquid dosage form required

5. Alter the absorption kinetics by reducing drug particle size

True or false: Suspensions should settle slowly and / or should be readily redispersed upon shaking?

True

In preparing a suspension of a powdered substance, the material to be suspended the solid particles must be first _________________?

wetted by the liquid medium

A wetting agent is also necessary to ___________?

avoid clumps of insoluble drug from forming during the preparation of the formulation.

The wetting agent lowers the_____ and _______ between the solid drug particles and the liquid and facilitates wetting of the drug particle surface.

interfacial tension and contact angle

A wetting agent also aids the production of a _____ ____ of the particles in the suspension.

uniform dispersion

Wetting agents include:
-
-
-

--Surfactants (tweens and spans)

--Hydrophilic colloids (acacia, alginates)

--Solvents (alcohol, propylene glycol, glycerin)

In a __________ suspension, particles settle quickly but easily resuspended on shaking.

Flocculated suspension

In a ___________ suspension, Particles remain suspended and settling is retarded by suspending or thickening agents and the dispersion media.

Deflocculate suspension---caking can occur over a long period of time---weeks or years

As floccules sediment they trap ____ and are easier to resuspend than if the particles settle into a tighter aggregate without the trapped ______.

solvent, solvent

The equilibrium between the attractive ________ forces and the repulsive __________ determines whether a flocculated or deflocculated suspension is formed.

van der Waals

electrostatic charges

_____________ arise from the interaction in the electrical double layer. Leads to forces of repulsion for particles with surface charge of the same sign

Electrostatic forces

True or False: For the Electrical Double Layer, we are interested in both charges of both the inner layer as well as the charges of the Zeta potential?

False--for the EDL, we are only interested in the charge of the Zeta potential

Floccules form when weak attractive ________ forces are holding the particles together

van der Waals

The _______ layer and the ________ layer make up the EDL.

stern and diffuse layer

The _________ is the net electrical charge of the electrical double layer.

Zeta potential

The larger the zeta potential the _____ is the charge density and the _____ is the force of mutual repulsion that keeps particles apart.

greater, greater

The _______ represents the electrical potential difference between the "surface charge" of the suspended particle and the bulk dispersion medium.

Zeta potential

__________ as flocculating agents can be used to lower the zeta potential, therefore lowering the electrostatic repulsion effects, and a floccul can form.

Electrolytes

Rate of settling is defined by the Stokes Equation:

= dx/dt = d2(ρi-p)g/18η

Remember you convert the diameter to _________?

cm

The rate of settling of a deflocculated suspension can be controlled by altering what two parameters?

1. Decrease particle size

2. Increase viscosity (by changing vehicle)

_______________ are physiologically inert substances which increase viscosity when added to suspensions.

Suspending agents

A second important function for suspending agents is to facilitate redistribution of a _______________.

suspension on shaking

For a coarse suspension: Particles are larger than ____________?

1 µm

For a Colloidal suspension: Particles are less than__________ in diameter?

1 µm

A ______________ suspension, when dispersed allows for a greater uniformity of dosing?

Deflocculated

A ___________ suspension is less elegant in appearance?

flocculated

Factors affecting the stability of suspension formulations:
1.
2.
3.

1. Crystal growth - Oswald ripening may occur leading to increase in drug particle size

2. Most drugs do have a finite solubility and its solution s

3. Microbial growth within the suspension--use preservatives such as sodium benzoate

An ______ is a dispersion of two immiscible liquids, one of which is finely subdivided and uniformly distributed as droplets (the dispersed phase) throughout the other (the continuous phase).

emulsion

If the oil is dispersed in the aqueous medium, it is ______ emulsion.

an oil in water (o/w)

If the water is dispersed in the oil, it is said to be __________ emulsion.

a water in oil (w/o)

True or False: Both o/w and w/o systems require an emulsifying agent in the formulation to maintain the dispersion?

true

Advantages of pharmaceutical emulsions are:
1.
2.
3.

1. Stable and homogeneous mix of two immiscible liquids.

2. Reduced particle size of oil globules in o/w emulsion renders oil more digestible and better absorption (increased surface area)

3. Masks taste, e.g., cod liver oil, mineral oil, castor oil emulsion (Neoloid)

Emulsions are formed when the ____tension between two immiscible liquids is lowered using an emulsifying agent

interfacial

In an emulsion, an energy source is provided to overcome the surface tension and increase the surface area of the disperse phase by decreasing the ________________?

decreasing the droplet particle size

Many times this energy source is the hand of the pharmacist

The properties of an ideal emulsion include:
1.
2.
3.
4.
5.

1. Homogeneous system
2. Small droplet size (0.5 - 2.5 μm)
3. Disperse phase should not aggregate on standing
4. No creaming of large droplets at the surface
5. No cracking - separation of the two phases

Emulsifying agents are categorized using the _____ system.

HLB system

The emulsifying agent should not be too _______ or too _____, so as to act at the interface rather than preferentially distributing to one of the phases.

hydrophilic or too lipophilic

_____________ are emulsifying agents that are anionic in nature and form hydrophilic colloids when added to water and produce o/w emulsions

Carbohydrates

________ are emulsifying agents that produce o/w emulsions, as seen in milk.

Proteins

In selecting and emulsifying agent, use one with a ______________ value similar to the value assigned to the oil in either an o/w or a w/o emulsion.

HLB

__________ are emulsifying agents have hydrophilic and lipophilic groups. Anionic, cationic and nonionic forms are used.

Surfactants - e.g. spans and tweens

----------are emulsifying agents that consists of finely divided solids having balanced hydrophilic lipophillic properties. They accumulate at the oil/water interface and form a coherent interfacial film around the droplets of dispersed phase globules and prevent coalescence. The emulsions formed using finely divided solids are stable and less prone to microbial contamination. Used to form o/w emulsions

Colloidal clays

____ are incorporated to improve the stability of the emulsion. It inhibits oxidation, but must be compatible with other ingredients.

antiooxidents

___________ in the amount of 12%-15% based on the external phase volume is frequently added to orally used o/w emulsions as a preservative.

Alcohol

__________ is the science of the flow of matter.

Rheology

__________ is the resistance of flow offered by a substance as a force is exerted on it.

Viscosity

Shearing stress is also called_________?

force----shear stress is the force per unit area

Shear rate is also called ______________?

flow------shear rate is the velocity difference b/w the planes

When the relationship between shear stress and shear rate is directly proportioned, it is described as a _____________________ fluid.

Newtonian

If you plot a rheogram of shear rate (y -axis) vs shearing stress (x-axis), you will get a straight line with a slope equal to_______________?

1/viscosity.

The viscosity of Newtonian fluids can be measured using equipment such as the _____?

Ostwald U-tube viscometer

Complex disperse systems such as emulsions and suspensions are examples of materials that are _________________ Fluids

Non-Newtonian

________ viscosity (ν) takes into account the density of the substance.

Kinematic

Systems which do not move when you first add force but then begin to move after a minimum amount of force is added are called _________.

Plastic flow--------once these systems move, the addition of force causes a linear increase in the rate of shear and Newtonian flow is exhibited.

Substances that exhibit plastic flow may also be called _____________________.?

Bingham Bodies

For plastic flow, you want a suspending agent that exhibits a yield value at ________ concentration and ________ viscosity.

Low, Low

___________ substances begin flowing as soon as a shearing stress is applied, therefore they do not have a yield value.

Pseudoplastic---example ketchup

For Pseudoplastic flow, with ___________ shear stress, the shear rate increases and these materials are often referred to as shear-thinning systems

increasing,

Pseudoplastic flow is common in pharmaceutical suspensions. In these cases, there is an apparent _______ in viscosity as the rate of shear increases

decease

Solutions of sodium carboxymethylcellulose and other cellulose esters show this characteristic

Systems which get more viscous as more force is added are called _____?

Dilatant

If a system changes its viscosity with time it is call a_______ system. .

thixotropic

_________________ is unique and only occurs in Non-Newtonian flow situations.

Thixotropic flow

A thixotropic fluid undergoes a decrease in viscosity with time, when subjected to ___________.

constant shearing

Factors affecting rheological properties & viscosity:
1.
2.
3.
4

1. Temperature (viscosity of liquid dec with temp inc)

2. shear rate
3. time
4. pressure (inc in pressure tend to increase viscosity)

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