Suspensions 1 Flashcards
1
Q
What is a Suspension ?
A
A coarse disperse system where an insoluble solid is dispersed in a liquid medium
2
Q
In the Disperse phase, solid particles are usually what size ?
A
Greater than 0.1 micrometre
3
Q
The disperse medium is usually an aqueous media. TRUE or FALSE
A
TRUE
4
Q
The disperse medium may infrequently be ?
A
An Organic or oily material
5
Q
Why do we need suspensions
A
- Drugs are predominantly insoluble
- Drugs are more stable in a suspension (or emulsion) than in any other dosage form (drug may degrade more readily if in solution)
- Able to control rate of release of drug if needed
- Drug may have bad taste; suspension may increase compliance
On a whole, needed for STABILITY and COMPLIANCE
6
Q
Suspensions are usually chemically and physical stable. TRUE or FALSE
A
TRUE
7
Q
Although the particles in suspensions are solid (therefore more chemically stable), the overall product behaves like a liquid. TRUE or FALSE a what does this ensure ?
A
TRUE, this ensures good compliance
8
Q
Why does compliance to suspensions tend to be good ?
A
- Easy to swallow (children and elderly)
- Easy to divide and control dose
- Masks unpleasant tastes (e.g: Chlorampenicol suspension; ester forms more acceptable taste)
- Fast pharmaceutical action
9
Q
Give two examples of antacid oral suspensions
A
1) Aluminium hydroxide
2) Magnesium hydroxide
10
Q
Give one example of Parenteral supensions
A
- Insulin Zinc suspension BP
11
Q
Give one example of Topical suspensions
A
- Calamine lotion BP
12
Q
Give an example of a dry powder used for suspensions
A
- Barium sulphate for Suspension BP
13
Q
Give an example of an insoluble/poorly soluble drug used in suspension
A
Prednisolone suspension
14
Q
Give an example of a drug used in suspension to prevent degradation and improve stability of a drug
A
Oxytetracycline suspension
15
Q
What drug is used in suspension to mask the bitter taste of some drug ?
A
Chloramphenicol palmitate suspension
16
Q
Give examples of drugs used in parenteral application (in order to control the rate of drug absorption)
A
Penicillin, Procaine
17
Q
Give an example of a vaccine formulated in suspension
A
Cholera vaccine
18
Q
Give an example of an x-ray contrast agent formulated in suspension
A
Barium sulphate
19
Q
State two desirable properties of suspensions
A
1) The dispersed particle should settle slowly
2) Particles should remain flocculated and be readily dispersed upon shaking. CAKING SHOULD BE AVOIDED
3) Viscosity should be appropriate.Not too thick or thin
4) Particle size - should remain reasonably constant
20
Q
State an advantage of dispersed particles settling slowly ?
A
This allows an accurate and uniform dose to be taken from the medicine
21
Q
Define flocculation
A
Easily distributed
22
Q
Define Caking. Why should this be avoided in suspensions
A
Aggregation of particles.
Should be avoided as this affects uniformity of drug distribution and physical stability / re-suspension of product
23
Q
Why does viscosity of suspensions matter ?
A
The product should be easily dispersed from its container
24
Q
Why should particle size be reasonably constant in suspensions
A
Particle size affects stability, re-dispersion and may minimise caking and settling of suspended material
25
How does particle size affect texture ?
Larger particles, generally over 5 micrometers in diameter result in a gritty texture
26
Particle size control is important as it affects factors such as ?
- Texture
- Uniformity of dose
- Variable dissolution and bioavailabilty
- Sedimentation; (which then affects Physical stability and dose uniformity)
27
Explain Sedimentation
Particles fall under force of gravity according to STOKES LAW
28
We defne the sedimentation volume, F as
The ratio of Vu/Vo
29
Powders may float on top of a liquid. State 3 factors this is often due to ?
1) The presence of an absorbed layer of air
2) The lipophilic nature of certain materials/contaminants
3) Poor properties of 'wettability' - refers to contact angle and the surface
30
What is Contact angle ?
The angle at which liquid or vapour meets a surface -the surface generally being solid
31
In the case of wetting of suspensions, the surface is the surface of the bulk liquid
The droplet is the powder being placed in contact with it.
TRUE or FALSE
TRUE
32
Contact angle depends on particle shape and this determines the degree of interaction
*LEARN*
33
Do hydrophobic powders have high or low contact angles ?
High
34
Do hydrophilic powders have high or low contact angles ?
Low
35
Why do hydrophobic powders have a high contact angle ?
Give examples of hydrophobic powders
They are not easily wetted and tend to float on the surface of the liquid.
e.g: Sulphur or Magnesium stearate
36
State an advantage (on wetting) of hydrophilic powders having a low contact angle ?
Give examples of hydrophilic powders
They are easily wetted
e.g: Zinc oxide and Magnesium Carbonate
37
Particle wetting can be improved by using 'wetting agents'
*LEARN*
38
```
Only wettable (and “wetted”) particles can be
readily dispersed into the liquid and remain
adequately dispersed
```
*LEARN*
39
Wetting agents improve wettability of hydrophobic powders. How ?
1) They reduce surface tension between particle and liquid surface
2) Reduce contact angle
40
Name 3 types of materials/wetting agents used to improve particle wetting
1) Surfactants
2) Solvents
3) Hydrophilic colloids
41
Choice of material used to improve particle wetting is dependent on ?
The route of administration
42
Give an example of surfactants commonly used as a wetting agent for the oral route
Polysorbates sorbitan esters (Tweens ans Spans)
43
Give examples of surfactants commonly used for via i.v route
Lecithin, Polysorbates and Poloxamers
44
State a disadvantage of surfactants as a wetting agent
They may cause excessive fming in the product
45
Surfactants should be used in relatively low concentrations when used as wetting agents (0.1% w/w).
*LEARN*
46
Give examples of hydrophilic colloids used as wetting agents
```
Acacia
Bentonite
Tragacanth
Alginates
Xantham gum
Carious cellulose derivates
```
47
Due to the viscosity of Hydrophilic colloids, they are also able to act as ...... agents ?
Suspending agents
48
Upon coating with a layer of hydrophilic colloid, particles intended for suspension become more 'wettable'.
Why do you want 'wettable' particles ?
*LEARN*
Only wettable particles are readily dispersed into the liquid and remain adequately dispersed.
49
State examples of Solvents that can be used as wetting agents
Alcohols e.g: Ethanol
Glycerol
Glycols
50
Different solvents exert a range of effects such as the ability to penetrate into loose aggregations of particles.
By doing this, they are able to displace the air adsorbed with the structure.
*LEARN*
51
Flocculation describes the removal of a sediment from a fluid.
*LEARN*
52
What does Flocculation describe ?
The removal of a sediment from fluid
53
What is the IUPAC definition of Flocculation
'A process of contact and adhesion whereby the particles of a dispersion form larger-size clusters'
54
In addition to occurring naturally, flocculation ca be forced, through agitation or ?
Addition of flocculating agents
55
State an example of a flocculating agent
Aluminium sulfate
56
Compare the behaviour of particles in a deflocculated and flocculated system
Compare behaviour of supernatant (liquid that lies above sediment)
1) Particles remain independent in deflocculated system whereas in flocculated system link together to form a loose structure
2) Particles settle at different rates but overall slowly whereas in flocculated system; big and small particles settle together in a loose structure
3) Settled particles may cake which is difficult to redisperse whereas in flocculated system; sediment remains loose and is easier to redisperse
- Supernatant remains turbid for a long time (due to particles settling slowly) whereas in flocculated; supernatant quickly becomes clear (particles settle quicker and together)
57
Increased viscosity increases or decreases ease/rate of suspension
decreases
58
State an advantage of high viscosity on flocculation
Increased viscosity helps in the short term but upon storage a high viscosity can make a product difficult to redisperse
59
What 3 factors need to balanced when formulating a suspension
Viscosity, Degree of flocculation and Ease of resuspension
60
In a deflocculated system, the sedimentation volume is given by what equation ?
Fu = Vu / Vo (in which Fu value should be as low as possible)
61
In a flocculated system, sedimentation volume is give by what equation ?
Ff = Vf / Vo
62
The degree of flocculation is given by ?
B (beta sign) = Ff/Fu = Vf/Vu
-The bigger the B value, the better the flocculation
63
Learn/ Draw diagrams for Deflocculated, flocculated ad Flocculated plus suspending agents system
*LEARN*
64
What materials can be used to control flocculation
- Electrolytes
- Polymers
- Viscosity modifiers
- Other additives ...
65
Zeta potential describes the electrical potential in the interfacial double layer at the boundary between different regions. For example in a suspension bw/n the solid and liquid particles
*LEARN*
66
What does zeta potential describe ?
The electrical potential in the interfacial double layer (at the boundary between different regions)
67
Why is the concentration of electrolytes important in suspension
It is important in maintaining the stability of the suspension
68
What is the effect on suspensions of electrolyte concentration being too high ?
If conc of electrolytes is too high, this may result in charge repulsion and caking of suspended agent
69
Electrolyte concentration can be controlled by buffering the formulation to control the pH and ionisation
*LEARN*
70
Polymers can be used to control flocculation as they encourage bridge flocculation. TRUE or FALSE
TRUE
71
State 4 examples of polymers that can be used to control flocculation
- Starch
- Alginates
- Tragacanth
- Cellulose derivatives
72
Why is selecting the correct polymer important for suspensions ?
It is important for determining viscosity of the liquid phase for example
73
State examples of Viscosity modifiers used in suspensions
- Polysacharrides
- Alginates; Starch; Xanthan gum
- Water-soluble celluloses
- Hydrated silicates; Bentonite and Veegum (MgAl Silicate)
- Carbomers
74
State 2 examples of polysaccharides commonly used in suspensions
Acacia: Thickener often used in extemporaneous dispensing
Tragacanth: Also used in extemporaneous products, Slow to hydrate, Non-newtonian behaviour
75
What are Carbomers ?
Synthetic polymers of acrylic acid
76
State 2 properties of Hydrated silicates
- Highly absorbent
| - Non -newtonian
77
State 5 'other additives' used to suspensions
- Buffering agents
- Flavours
- Colouring agents
- Preservatives
- Sweetners
(Artificial (E954 saccharin, E951 aspartame) and 'natural' materials)
78
State 4 different methods used to manufacture suspensions
- Extemporaneously (mortar and pestle)
- High - shear mixers
- Homogenisers
- Ball mills
79
State the IUPAC definition of 'Ostwald Ripening'
The change of an inhomogenous structure over time.
Over time, small crystals dissolve and redeposit onto larger crystals
80
Suspensions contain particles suspended in saturated or supersaturated solutions of the drug substance.
What does this mean in thermodynamic terms ?
Small particles will tend to dissolve and large particles will tend to get larger.
As a result, the system will change and become unsuitable for use
81
Describe Ostwald ripening of in terms of solubility and particle size
Solubility of particles depends on their particle size. As size (r) decreases, solubility increases
82
*Write ostwalds equation*
*write and check slide 36 if correct*
83
Define Polymorphism
Substances existing in more than one crystalline form despite being chemically 'identical'
84
Different polymorphs have different properties and this can affect physical stability and solubility. TRUE or FALSE
TRUE
85
Polymorphism exists in spironolactone, paracetamol and cortisone. TRUE or FALSE
TRUE
86
How many common crystal forms does cortisone acetate suspension have ?
5 common crystal forms
87
Four unstable forms of cortisone acetate suspension can change to the stable form in the presence of ?
Water
88
Caking is often observed when crystals change form. TRUE or FALSE
TRUE
89
Why must materials be prepared in their correct crystal form only ?
because unstable crystal forms can change to the stable form in the presence of water and this often results in caking
90
State 3 materials that can inhibit crystal growth and how ?
- Polymers
Form a protective layer around particles
- Surfactants
Reduce crystallisation
- Temperature
Influences solubility and this can change the degree of saturation/supersaturation in solution
91
State methods of physical stability evaluation of suspensions
- Aesthetic tests (General appearance, Colour, Odour, Taste)
- pH (measurement of zeta [potential and solubility)
- Sedimentation rate
- Particle size and form (crystalline and not)
- Redispersion and centrifugation tests
- Rheological measurements
- Freeze-thaw temp cycling
- Compatibility with container and cap liner
- Dose uniformity
- Microbial testing
92
Chemical degradation usually occurs in solution phase of a suspension. TRUE or FALSE
TRUE
93
Chemical degradation may result in a change of pH and therefore physical stability. TRUE or FALSE
TRUE
94
State the constituents of Calamine Lotion BP suspension formulation
Calamine 30g
Zinc oxide 10g
Bentonite 6g (thickening agent)
- Sodium citrate 1g (controls flocculation)
- Liquified phenol 0.5ml (preservative)
- Glycerol 5ml (thickener; also helps product to adhere to skin)
- Water to 200ml
