Phar 321 - Theory Of Pharmaceutical Suspension

Front 1

Define: pharmaceutical suspension

Back 1

A coarse dispersion (>500nm) where insoluble/ lyophobic solid particles are dispersed in a liquid (aqueous or oil) solution.

These are 2 phase/ heterogenous solutions.

Front 2

Define: lyophobic.

Back 2

Solvent-hating

Front 3

What are the advantages to pharmaceutical suspensions? (6)

Back 3

1. Good for API with low solubility

2. Masking taste of API

3. Good for patients that can't swallow tablets

4. Controlled drug delivery

5. Avoid/ reduce amount of co-solvents

6. Improves API resistance to degradation by hydrolysis, oxidation, or microbes

Front 4

What are disadvantages to pharmaceutical suspensions? (3)

Back 4

1. Unstable, so formulation must last shelf-life

2. Hard to make pharmaceutically elegant

3. Bulky and difficult for patients to transport

Front 5

What are properties of an ideal suspension? (4)

Back 5

1. Should have a slow settling phase and remain homogenous long enough for patient to shake and pour.

2. Sediment must be easily resuspended

3. Optimal viscosity to increase settling time but also easy of use for patient

4. Must taste good; no gritty texture

Front 6

What are the important interfacial properties of suspensions? (2)

Back 6

1. Surface free energy

2. Surface potential

Front 7

The suspension is more stable when delta G is:

a. larger

b. smaller

Back 7

b. smaller

Front 8

Pharmaceutical suspensions have a ____ amount of free energy.

a. large

b. small

Back 8

a. large

Front 9

A system of smaller dispersed particles is ____ thermodynamically stable because of the ____.

Back 9

1. Less

2. High total surface area.

Front 10

How do particles of suspensions reduce surface area?

Back 10

Particles agglomerate.

Front 11

What is the purpose of wetting agents?

Back 11

They are added to suspensions to prevent agglomeration by reducing surface free energy, which helps the particles stay suspended and increase stability.

Front 12

What is surface potential?

Back 12

Surface potential exists when solid particles have a charge in relation to the liquid medium.

Front 13

How can solid particles in suspensions become charged?

Back 13

1. Selective adsorption of electrolytes in the solution

2. Ionization of wetting agents on the surface of the particle

3. Ionization of the functional groups on the API

Front 14

In the electric double layer theory (EDLT), what are 1. co-ions and 2. counter-ions?

Back 14

1. Co-ions are ions that have been selectively adsorbed by a solid particle, which gives the particle a charge.

2. Counter-ions are oppositely charged to co-ions and are bound to the particle surface.

Front 15

Describe the stern layer in terms of 1. location and 2. ions found in that layer.

Back 15

1. The stern layer is located right next to the solid particle

2. Only counter-ions are found

Front 16

Describe the shear layer in terms of 1. location and 2. ions found in that layer.

Back 16

1. The shear layer is the layer that is separated from the solid particle by the stern layer. The plane between the stern layer and shear layer is called the stern plane.

2. It is a diffuse layer but contains more counter-ions than co-ions. This layer ends when the counter-ions and co-ions are found in equal concentration.

Front 17

Why are suspensions as a whole electrically neutral, despite the presence of unequal distribution in the double layers?

Back 17

The bulk of the solution consists of solvent containing equal concentration of co-ions and counter-ions.

Front 18

Define: nernst potential

Back 18

The difference between the electric potential in the actual/true surface of the particle and the electroneutral region of the dispersion medium.

Front 19

Define: zeta potential

Back 19

The difference between the potential in the shear plane and electroneutral region.

Front 20

What happens to the particles in a suspension if the zeta potential is reduced?

Back 20

The attractive Van Der Waal forces overcome the forces of repulsion between particles.

Particles join to form floccules.

Front 21

What prevents wetting of solid particles? (2)

Back 21

1. Particles can be hydrophobic

2. A layer of air, greasy material, or impurities cover the solid particle

Front 22

Wetting agents can decrease the contact angle/ interfacial tension of these different phase: (2)

Back 22

1. Solid to liquid

2. Liquid to vapour

Front 23

What concert costs 45 cents?

Back 23

50 Cent featuring Nickelback.

Front 24

If the [surfactant] is too high, what may occur in the suspensions?

Back 24

It may foam or cause the particles to deflocculate. Both are unwanted.

Front 25

How do surfactants act as wetting agents?

Back 25

The hydrocarbon chain is adsorbed into the hydrophobic particle surface. The hydrophilic/ polar end remains in the aqueous medium.

Front 26

What is the HLB (hydrophilic lipophilic balance) value typically?

Back 26

Between 7 and 9.

Front 27

Which surfactants are used in oral suspensions? (3)

Back 27

1. Polysorbates

2. Sorbitan esters

3. SDS

Front 28

Which surfactants are used in parenteral suspensions? (3)

Back 28

1. Polysorbates

2. Poloxamers

3. Lecithin

Front 29

What are hygroscopic solvents/ levigating agents?

Provide examples.

Back 29

Agents that lower liquid/ air interfacial tension and help with liquid penetration into powder.

Examples: alcohol, glycerol, propylene glycol

Front 30

Describe the particle distribution of deflocculated and flocculated suspensions.

Back 30

Deflocculated: exists in separate entities

Flocculated: Form loose aggregates (flocs)

Front 31

Describe the sedimentation rate of deflocculated and flocculated suspensions.

Back 31

Deflocculated: Slow

Flocculated: Rapid

Front 32

Describe the sedimentation structure of deflocculated and flocculated suspensions.

Back 32

Deflocculated: Compact

Flocculated: Scaffold/ loose

Front 33

Describe the ease of redispersion of deflocculated and flocculated suspensions.

Back 33

Deflocculated: Difficult

Flocculated: Easy

Front 34

Describe the supernatant of deflocculated and flocculated suspensions.

Back 34

Deflocculated: cloudy

Flocculated: generally clear

Front 35

What does a nosy pepper do?

Back 35

It gets jalapeño business.

Front 36

When particles in a solution collide, what are the two possible results?

Back 36

Formation of aggregates or re-dispersion.

Front 37

According to the DLVO theory of suspension, the potential energy of interaction between the particles, VT, is a result from:

Back 37

Repulsion from the double later, VR

(depends on zeta potential)

And attractive Van Der Waal Forces, VA

(depends on radius and inter-particular distance)

VT=VR+VA

Front 38

What does the arrow signify?

What does the line on this graph signify?

Back 38

Vm is the maximum repulsive force between two particles. Also known as the energy barrier.

This line signifies VT.

Particles must have sufficient momentum to cross this barrier in order to conglomerate.

Front 39

Describe line A in terms of attractive and repulsive forces.

Back 39

VR >>> VA

Dispersion is highly stable because of the high net repulsive force.

This system does not aggregate/ form floccules.

Front 40

What do you call a bear with no teeth?

Back 40

A gummy bear.

Front 41

Explain point 5 on line B.

Back 41

Under the line = Van Der Waal attractive force.

There is a energy minimum here, and floccuation occurs where loose aggregates can be easily broken up with agitation and dilution.

Front 42

Explain point 4 on line B.

Back 42

The outer region of particles in the double layer start to touch.

Flocculated particles can come together, but any closer and repulsion forces build.

Front 43

Explain point 3 on line B.

Back 43

The double layers begin overlapping, causing the maximum repulsion forces.

Energy (such as increased temperature or graviation) must be added to push the particles together.

Front 44

Explain point 2 on line B.

Back 44

Particles start to touch, and coagulation/ caking occurs. The high energy magnitude causes particles to bind tightly together, and particles are very difficult to disperse.

Front 45

Explain point 1 on line B.

Back 45

Particles are crushing into each other with very high energy.

Does not normally occur in pharmacy situations.

Front 46

How do surfactants affect suspensions in terms of attractive and repulsive forces?

Back 46

Surfactants can be applied to particles with very low zeta potential (caking/ coagulation). This causes steric stabilization rather than electrical stabilization.

DVLO equation:

VT=VR+VA+VS

Front 47

Explain line C.

Back 47

VA>>VR

Rapid aggregation occur - system is unstable.

Front 48

What is Mozart doing right now?

Back 48

Decomposing.

Front 49

In deflocculated systems, the zeta potential is __ than the critical zeta potential.

Back 49

Greater

Front 50

How do cakes form in deflocculated systems?

Back 50

Small particles fill the void between larger ones. Pressure in the lowest layer forms cakes that are difficult to re-disperse.

Front 51

In flocculated systems, the zeta potential is __ than the critical zeta potential value.

Back 51

Smaller.

Attractive forces overcome repulsion forces, forming floccules.

Front 52

Methods of reducing rate of sedimentation:

Back 52

1. Decrease particle size

2. Increase viscosity of solvent (i.e. cellulose derivative, acacia)

3. Increase density of the continuous phase (i.e. add manitol or sorbitol)

Front 53

What is Stoke's law?

Back 53

Stoke's equation helps to explain settling kinetics.

Front 54

What are limitations to Stoke's law?

Back 54

1. Only works for dilute (<2% w/v) particles

2. Assume spherical monodispersed particles (all particles are same size)

3. Doesn't account impact of dispersed particles on viscosity

4. Does not account Brownian motion (random motion) which affects sedimentation

Front 55

Identify the variables of Stoke's equation:

Back 55

Front 56

What is the sedimentation volume?

What is the range of values?

Back 56

Sedimentation Volume (F) : ratio of equilibrium volume of sedimentation Vu, to total volume of suspension, Vo.

Ranges from 0 to 1.

Front 57

What is the degree of flocculation?

What is the range of values?

Back 57

Degree of Flocculation (B) : relates sedimentation volume of a flocculated suspension, F, to the sedimentation volume when deflocculated, F∞.

Front 58

How does adding electrolytes cause flocculation?

Back 58

Electrolytes reduce zeta potential, causing particles to come together.

Increased flocculation with increased valency.

Front 59

How does adding surfactants cause flocculation?

Back 59

Ionic surfactants neutralize charge on particles.

Non-ionic surfactants: the long structures get adsorbed onto more than one particle, forming flocs.

Front 60

How does adding polymers cause flocculation?

Back 60

Linear and branched polymers adsorb onto the surfaces of particles, holding them together in place.

Front 61

What are 3 excipients that can be added to cause flocculation?

Back 61

1. Electrolytes

2. Surfactants

3. Polymers

Front 62

Gritty texture is found in particles of what size?

Back 62

>5mcm

Front 63

Hypodermic needles clog when particles are what size?

Back 63

>25mcm

Front 64

Viscosity of a concentrated suspension can be increased with ___ particles.

a. Smaller

b. Larger

Back 64

a. Smaller

High surface area in total.

Front 65

The rate and extent of drug absorption is better with ___ particles.

a. Smaller

b. Larger

Back 65

a. Smaller

Front 66

Did you hear about the kidnapping at school?

Back 66

It's okay, he woke up.

Front 67

Which particle shape is more likely to clog needles?

a. Spherical

b. Irregular

Back 67

b. Irregular

Front 68

Which particle shape is more likely to cake/ coagulate?

a. Spherical

b. Irregular

Back 68

a. Spherical

Uniform shape is more likely to pack tightly.

Front 69

Why is a narrow particle size distribution favoured? (2)

Back 69

1. Causes a more uniform sedimentation rate

2. Limits Ostwald ripening

Front 70

Define: Ostwald Ripening

Back 70

The dissolution of small crystals or particles when the temperature increases, and the redeposition of the dissolved species on the surfaces of larger crystals when the temperature decreases.

This is because smaller particles have have more surface free energy, which allows small crystals to be more easily dissolved.

Front 71

How can you limit Ostwald Ripening? (3)

Back 71

1. Have a uniform distribution of particle size

2. Reduce temperature fluctuations

3. Add a surface active agent (binds to lipophilic surface of particle to reduce dissolution)

Front 72

Name examples of surface active agents. (3)

Back 72

1. Polysorbate 80

2. Carbamazepine

3. SDS

Front 73

Polymorphic drugs and particles are more soluble when they are:

a. Stable

b. Metastable

Back 73

b. Metastable

Front 74

Polymorphic drugs and particles are more likely to crystalize when they are:

a. Stable

b. Metastable

Back 74

a. Stable

Front 75

How an hydrophillic polymers act as a steric stabilizer?

Back 75

When particles coated with polymers approach each other, steric repulsion acts when the polymers overlap.

Front 76

At high concentrations, flow properties of a solution are pseudoplastic.

When under low shear stress, the viscosity of the system will be ____.

a. High

b. Low

Back 76

a. High

Front 77

At high concentrations, flow properties of a solution are pseudoplastic.

When viscosity of the system is high, the shear stress of the system is ____.

a. High

b. Low

Back 77

b. Low

Front 78

Define: thixotropy

Back 78

Time-dependent recovery of flow properties.

Front 79

What is the relative concentration needed to increase the viscosity of a solution with hydrophillic polymers?

1. Branched polymers

2. Linear polymers

Back 79

1. Low

2. High

Front 80

Which of the follow is a linear hydrophillic polymer?

a. Polyvinylpyrrolidone

b. Methylcellulose

c. Sodium Carboxymethylcellulose

d. Hydroxyethylcellulose

Back 80

a. PVP