1. Collodial Dispersions - aggregates of 0.001 to 1 um

2. Suspensions - solid particles > 1 um

3. Emulsions - liquid particles > 1 um in an immiscible liquid

4. Microemulsions- liquid particles < 0.1 um

1. Easy to swallow

2. Flexible dosing

3. Greater chemical stability because they have some parts of the drug in solid state

4. greater palatability

5. faster onset than oral solids-- they can bypass wetting and disintegration

1. Bulky/ heavy transport

2. Medium for microbial growth

3. Chemical instability vs a solid

4. lower physical stability because it settles

5. Potential dosing inaccuracies

1. solid drug is comminuted to a fine powder

2. Wetted

3. Suspended in a suitable vehicle

1. Ease of Production

2. Dosage Uniformity

3. Stability

4. Patient acceptance

5. Drug release

1. Particle size

2. Particle wetting

3. Physical stability

1. Micropulverization - 10 to 50 um

2. Jet Milling - < 10 um

3. Spray Drying - evaporates to fine particles

1. Electric grinders

2. Spatulation

3. Trituration

Reducing the particle size by rubbing in a mortar with a pestile.

A potent powdered drug is mixed with a suitable diluent.

We "wet" poorly soluble drug particles so they can be readily dispered in the continous phase.

To prevent clumping together or to prevent floating on top of the liquid

Hydrophobic side groups

or

Air pockets

1. Particle settling

2. Particle aggregation (clumping)

3. Particle growth

V = d^2 (r1- r2)g/ (18n)

V = falling velocity

d = sphere diameter

r1 = density of sphere

r2 = density of liquid

g = gravitational constant

n = viscosity of dispersion

If you have a bigger particle then it _______

If you have a denser particle then it __________

If you have a higher viscosity then __________

falls harder

falls faster

decreases the settling rate

As you decrease the particle size you end up increasing the S.A and thus the free energy of the system.  This decreases the ΔH stability.

So the system will tend towards the most ΔH stable state which is one with a lower exposed S.A. so it will clump together

1. Electrostatic repulsive

2. Van Der Waals Attractive

3. Repulsive hydration

4. Born repulsive

5. Adhesive

6. Steric repulsive

At the primary minimum

which occurs when they are close together

lower the primary minimum

bring the particles even closer together

Coagulation

and

Flocculation

1. They are strongly bound at the primary minimum

2. The particles are so closely aggregated that it makes them difficult to redisperse

3. Caking can occur

coagulation; settling

(it is the formation of a non-redispersible sediemnt w/in a suspension)

" loose and woolly"

or

weakly bound at the secondary minimum

1. Small particles dissolves

2. This supersaturates solution

3. Particles recrystallize to larger crystals

also

Bridges btwn new formed crystals can occur

Temperature fluctuations

(You want to avoid wide and repetitive temp changes)

1. Manufacture

2. Long term physical stability

3. Long term chemical stability

4. Long term microbiological stability

1. Wetting agents - help to disperse the solid

2. Flocculating agents - help keep them apart

3. Suspending agents - help keep them suspended

Surfactants-- coating makes more hydrophilic

Solvents that are water miscible- displaces air pockets

Certain polymers- ex: cellulose derivatives

1. Electrolytes - reduce the charge to reduce the electric barrier btwn particles

2. Surfactants - can form a hydration barrier with nonionic or increase charge repulsion when ionic

3. Certain polymers - can sterically prevent closeness. can also form bridges btwn them

1. dissolution and bioavailability depend on it.  the higher the viscosity the lower the dissolution

2. syringeability of injectables

3. consistency in topicals

4. Palatability of oral products. If it is more viscous then you have a slower diffusion to the taste bud, helps to mask taste

5. Stablizing dispersed dosage forms - a higher viscosity helps slow down settling (Stokes equation)

Shear Rate (G)

which is the rate of flow

Shear stress (F)

It reflects the force that is applied

V = F/G

Force/ Rate

Shear Stree/ Shear Rate

Shear Rate vs. Shear Stress

the slope is 1/ viscosity

Lower

(inverse relationship)

Straight line graph

Slope and thus Viscosity

When the minimum shearing stress is reached

or in other words

when the intramolecular forces have been overcome so the liquid "yields" to the force

The yield value

(the threshold it must reach before flow can occur)

Because flow occurs as soon as a stress is applied.  The increase in stress decreases the viscosity.

When on the shelf settling decreases becuase of the high viscosity

An aqueous dispersion of certain hydrocolloids.

These Long, High MW molecules are tangled but when stress is applied detangle to allow flow.

When the ST interactions are disrupted and the liquids "thins".  When under stress

This decreases the viscosity

Because on the stress is removed, the STs resume its interactions and the restrictive network slowly reforms.

We can see this occur when put on the shelf the product become more viscous.

Forming a hydrophilic colloid network.

with Hydrated, interacting macromolecules

That it is a suspending agent!

most common  = xanthan gum