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Suspensions Flashcards

1
Q

What is the definition of suspensions?

A

Dispersion of finely divided solid particles in a liquid medium

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2
Q

Coarse suspensions’ particle size is

A

> 1 micron

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3
Q

Colloidal suspensions’ particle size is

A

less than or = to 1 micron

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4
Q

Liquid medium may be

A

aqueous or non-aqueous

most pharmacy prep is aq

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5
Q

Applications of suspensions (there are 3 applications)

A
  1. For oral use (adm insoluble drugs in liquid form; form pleasant to taste; absorptive/antacid properties in treatment of gastric disorders)
  2. For injection (Release drug in slow and sustained manner depot therapy)
  3. For external use (apply insoluble drugs on skin)
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6
Q

What are some desirable properties of suspensions? (there are 7)

A
  1. Chemically stable
  2. Low rate of sedimentation of particles
  3. Particles readily dispersed upon gentle shaking of the container
  4. size of particle fairly constant throughout storage
  5. Pour readily from the container
  6. Suspensions for injections flow readily through the syringe needle
  7. Suspensions for external use spread easily and are not so mobile that they run off the surface when applied
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7
Q

What are some factors affecting the Stokes’ equation (sedimentation rate of particles)?

A

Particle size –> larger –> greater sedimentation rate

Denser of dispersion medium –> lower sedimentation rate

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8
Q

Why are flocculated suspensions more preferable than deflocculated suspensions?

A 
Nature of dispersed phase: aggregates
Rate of sedimentation: rapid
Porous sediment on prolonged standing; relatively large volume; easy to disperse
Clear supernatant liquid
Plastic flow with thixotrophy
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9
Q

Why are deflocculated suspensions not preferred?

A

Dispersed phase: individual particles
Slow sedimentation rate
Compact sediment (cake); relatively small vol, difficult to disperse
Cloudy supernatant
Dilatant flow; troublesome during production

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10
Q

What is the dispersed phase in a suspension?

A

the insoluble solid particles; aka suspensoid

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11
Q

What are lyophilic solids?

A

solvent-loving and don’t require use of wetting agent for dispersion in liquid vehicle

may also increase the viscosity of suspension

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12
Q

What are lyophobic solids?

A

Not solvent-loving and require wetting agent

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13
Q

Most drugs are lyophilic or lyophobic?

A

lyophobic

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14
Q

What is the liquid vehicle in a suspension

A

dispersion medium/continuous phase

can be aq/non-aq

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15
Q

What aq liquid is commonly used as a liquid vehicle?

A

water

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16
Q

What is the function of a wetting agent?

A

make solid particles more penetrable by the dispersion medium

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17
Q

MOA of wetting agents (2 modes of action)

A

1) Reduce solid-liquid interfacial tension

2) Imparts hydrophilicity to particle surface

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18
Q

How and where are the wetting agents added?

A

pre-mixed w solid particles in preparation of suspension

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19
Q

what are 3 examples of wetting agents for aq dispersion medium?

A
  1. surfactants (Span HLB 7-9) ; conc below cmc
  2. Hydrophilic polymers (acacia, tragacanth, xanthan gum, polyvinylpyrrolidone)
  3. Polyhydric alcohols (glycerin, propylene glycol, PEG) - miscible in water
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20
Q

which polyhydric alcohol should not be used for oral suspensions?

A

Diethylene glycol should not be used for oral suspension

Toxic and can cause death when consumed orally

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21
Q

Purpose of flocculating agents?

A

To induce flocculation

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22
Q

Electrolytes as flocculating agents affects _____

A

affect zeta potential which governs interparticulate repulsion/attraction

23
Q

When does interparticulate attraction occurs?

A

zeta potential reduced below critical value

24
Q

Low conc of electrolyte (0.01-1%); what happens to zeta potential?

A

reduce zeta potential to just below critical value –> interparticulate attraction
VDW attractive forces –> particles aggregates to form flocs
on prolonged standing, flocs settled to form porous sediment; easy to disperse

25
High conc of electrolyte (>1%) ; what happens to zeta potential?
reverses the sign of zeta potential; interparticulate repulsions prolonged standing, particles settle to form compact sediment; difficult to disperse
26
Low conc of electrolytes form flocculated or deflocculated suspension?
flocculated suspension
27
High conc of electrolytes form flocculated or deflocculated suspension?
deflocculated suspension Particles gradually orientate will they move slowly; repel by one particle, by another particle; slowly fill the voids --> minimum of interparticle volume
28
When the valence of electrolytes increases, the effectiveness of electrolyte in aggregating the particles ________
increases (Schulze-Hardy rule) - monovalent ion can also induce flocculation - divalent 10 times more and trivalent 1000 times more as effective as monovalent ions
29
Surfactant active agents - ionic agents acts as
electrolytes; carry a charge | zeta potential and valence
30
Non-ionic agents are used at conc ____ cmc
above cmc
31
How does the non-ionic agents work?
micelles adsorbed at surface of particles --> serve as bridges btw particles --> flocculation
32
Is low or high conc of hydrophilic polymers preferred?
low conc (<0.05%) - to give flocculating effect
33
How does hydrophilic polymers work?
adsorbed at surface of particles --> serve as bridges btw particles --> flocculation
34
high conc of hydrophilic polymers causes ________ effect and ____________ effect
1. Protective colloid effect (0.05-1%) | 2. Viscosity-enhancing effect (>0.1%)
35
What is Protective colloid effect ?
Polymer forms protective coat around each particle, separating them from one another
36
What is Viscosity-enhancing effect?
Polymer increases viscosity of medium and improves stability BUT reduces flowability of suspension
37
Purpose of thickening agent?
- assist in suspension of solid particles; thickening dispersion medium - To prevent rapid sedimentation rate - Thicken dispersion liquid medium; enhance viscosity
38
3 types of flocculating agents
1. electrolytes 2. surface active agents 3. hydrophilic polymers
39
Examples of thickening agents?
hydrophilic polymers; gums, gelatin, bentonite, CMC, cellulose, PVP different concentration hydrophilic polymers gives diff effect: - flocculating effect <0.05% - protective colloid effect (0.05-0.1%) - viscosity enhancing effect (>0.1%)
40
functions of pH buffers?
- provide optimal stability of suspension | - indiscriminate use should be avoided
41
Functions of preservatives?
- control microbial contamination | - cationic preservatives generally not recommended
42
Functions of colorants, flavours and fragances?
most are oily liquids which may affect the stability of suspensions
43
What are the 2 ways to prepare suspensions?
1) dispersion technique | 2) precipitation technique
44
How does the dispersion technique works? (in the lab)
1. mix solid (drug) with wetting agent in mortar 2. add small portion of liquid vehicle containing additives to produce a pourable mixture 3. transfer to measuring cylinder and add the remaining liquid vehicle
45
Why excessive shearing should be avoided in large scale dispersion technique?
Drug particle size gets smaller, specific surface area (SA/weight) larger Dissolution rate of drug upon adm will be large; if rate higher may be desirable/undesirable radius decreases, velocity of fall or rise of particle decreases; viscosity might be affected too
46
How does the organic solvent precipitation works?
water-insoluble drug dissolved in water-miscible organic solvent and then added to distilled water under standard conditions
47
How does pH-induced ppt works?
only applicable to drugs whose solubility is affected by pH
48
How do we evaluate the suspensions? 2 ways
1) stability of suspension | 2) redispersibility of suspension
49
How do we measure stability of suspension
volume of sediment at time t (Vt) / initial vol of total suspension (V0) = index of stability (F) F = Vt/V0 or Ht/H0 where Ht: height of sediment, H0: height of total volume in cyclinder
50
How do we read the index of stability?
When F = 1; 100% stable | over time, F < 1
51
How do we measure redispersibility of suspensions?
Allow the dispersed phase to settle down first before shaking it (mechanical device used to shake) Number of shakes required to disperse the sediment is determined
52
How do we read redispersibility of suspensions?
The ease of redispersibility is inversely prop to number of shakes
53
2 different methods to prepare suspensions?
- dispersion technique - precipitation technique - -> organic solvent precipitation - -> pH-induced precipitation
54
explain the dispersion method for a large scale production
- premix solid (drug) and wetting agents in a mixer - add dispersion medium (liquid vehicle containing additives), ensure pourable mixture first - transfer mixture to high shear equipment to produce a good dispersion note: excessive shearing is avoided

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