Pharmaceutics Flashcards
(169 cards)
1
Q
What is rheology?
A
The science of flow. Describes the flow of liquids and deformation of solids.
2
Q
Two underlying concepts of rheology?
A
1) Intermolecular forces and bonding
2) timetable of experimental observations
3
Q
What is viscosity?
A
An expression of the resistance of a fluid to flow
4
Q
What did Hooke define?
A
an ideal elastic solid
5
Q
What did Newton define?
A
An ideal liquid
6
Q
What does viscoelastic mean?
A
Having both liquid and solid character
7
Q
Newton’s law of flow states?
A
The rate of flow is directly proportional to the applied stress
8
Q
What is shearing stress?
A
The force per unit area to bring about flow
9
Q
What is a Newtonian fluid?
A
Viscosity does not chance with increased shear rate, only with temperature
10
Q
How to tell a Newtonian fluid on a graph?
A
proportional and linear
11
Q
What is viscosity measured in?
A
poise or Pas
12
Q
What is the Mark-Houwink equation for?
A
Determining molecular weight from viscosity
13
Q
Types of non-newtonian fluids?
A
Shear-thinning (pseudoplastic)
Shear-thickening (dilatant)
Bingham (plastic)
14
Q
Emulsion definition?
A
An emulsion is a thermodynamically unstable mixture of two immiscible liquids. One of the liquids is dispersed as globules inside the other. They are stabilised by an emulsifying agent.
15
Q
What types of emulsions are there?
A
Oil-in-water
Water-in-oil
Double emulsions
16
Q
What is the most common type of emulsion?
A
Oil-in-water
17
Q
What are oil-in-water emulsions used for?
A
Oral
Injectable
Ophthalmic
Topical
18
Q
Oil-in-water emulsions require what kind of emulsifying agent?
A
Hydrophilic
19
Q
Examples of hydrophilic emulsifying agents?
A
Sodium lauryl sulfate
Triethanolamine sterate
Sodium oleate
Glyceryl monostearate
20
Q
What are water-in-oil emulsions used for?
A
Mainly topical application
21
Q
Water-in-oil emulsions require what kind of emulsifying agent?
A
Lipophilic
22
Q
Examples of lipophilic emulsifying agents?
A
Calcium palmitate
Sorbitan esters
Cholesterol
Wool fats
23
Q
How to identify the phases of an emulsion?
A
1) Add a small quantity of water-soluble dye (e.g. Methylene blue) to the surface. If dissolves uniformly throughout it is an oil-in-water, if the dye lies in clumps on the surface it is water-in-oil
2) Dilute emulsion with water. If it mixes freely it is an oil-in-water
3) Apply current to emulsion via electrodes. If current carried across it is oil-in-water
24
Q
Why do two immiscible liquids not mix?
A
They have higher cohesive forces than adhesive forces.
O and H in water bond with surrounding water molecules through dipolar and hydrogen bonds.
C in oil bond with surrounding molecules through weak hydrophobic and Van der Waals forces
25
What are the three emulsion theories?
Surface tension theory
Interfacial film theory
Monomolecular adsorption/ orientated-wedge theory
26
What is surface tension theory?
1) to form an emulsion the phases need to interact and overcome interfacial tension
2) when one phase is broken into small globules the interfacial area is much greater than the minimum surface area of that liquid in a phase separated system
3) adding an emulsifying agent lowers interfacial tension by adsorbing to the interface on the globule, allowing phases to interact
27
What is interfacial film theory?
An emulsifier located at the interface between oil and water phases forming a thin film by being adsorbed onto the surface of dispersed globules
Film needs to be rigid enough to establish the interface but flexible enough that collision of globules does not rupture film
28
The main difference between surface tension theory and interfacial film theory?
In surface tension theory the emulsifier absorbs to the globule in separate ‘bridges’, whereas in interfacial film theory the emulsifier creates a film all around
29
What is orientated-wedge theory?
Assumes formation of a monomolecular layer of emulsifier around the globule
Emulsifiers orientate themselves around the globule according to their solubility.
Emulsifiers are amphiphilic.
Prevent coalescence when globules become too close to each other
30
Why are there different emulsification theories?
Because of the different types of emulsifiers
31
What are the three main groups of emulsifiers?
Surface active agents (surfactants)
Hydrophilic colloids
Finely divided solid particles
32
How do surfactant emulsifiers work?
Adsorbed at the oil-water interface to form a monomolecular film and reduce interfacial tension
33
How do hydrophilic colloids work as emulsifiers?
Form a multimolecular film around the dispersed globules of an oil-in-water emulsion
34
How do finely divided solid particles work as emulsifiers?
Adsorbed around dispersed globules
35
What is the most common type of emulsifiers?
Surfactants
36
What does surfactant stand for?
Surface-active agents
37
What is a key property that determines the type of an emulsifier?
Hydrophilic-lipophilic balance (HLB) value
38
What HLB value is needed for an oil-in-water emulsifier?
9-12
39
What HLB value is needed for a water-in-oil emulsifier?
3-6
40
What is the Bancroft rule?
The phase in which an emulsifier is more soluble constitutes the continuous phase
41
How are emulsions made?
1) homogenised (mixed)
2) Two phases assembled separately and then combined by slowly adding the dispersion phase to the continuous phase with constant mixing
3) If an oil-in-water emulsion has more than one emulsifier then the higher HLB value should be added first
4) Volatile(flavours) and thermosensitive ingredients added after emulsion formed
5) APIs can be pre-dissolved in one of the phases or added at the end depending on the drugs solubility, stability and partitioning properties
42
What can go wrong with emulsions?
Stability issues
Chemical instabilities
Microbial issues
43
What is creaming?
The upward movement of less dense dispersed oil globules in an oil-in-water emulsion.
Visually evident with separation of layers.
Reversible by shaking
44
What is sedimentation?
The downward movement of more dense dispersed water globules in a water-in-oil emulsion.
Visually evident with separation of layers.
Reversible by shaking
45
What is the difference between creaming and sedimentation?
Creaming occurs in oil-in-water emulsions whereas sedimentation occurs in water-in-oil emulsions
46
What is Stoke’s law?
models creaming and sedimentation in an emulsion. Can be used to enhance physical stability of emulsions
47
How to enhance the stability of an emulsion?
Decrease globule size to <5micrometers
Increase viscosity of the system, such as adding hydrophilic polymers to the continuous phase if oil-in-water emulsions
Decreasing interfacial tensions, such as adding hydrophilic polymers to the continuous phase if oil-in-water emulsions
Reduce the density differences between the two phases
48
What is aggregation/flocculation?
It involves the close packing of the dispersed phase, but the globules do not fuse.
It is reversible to an extent.
49
What is coalescence?
When emulsified globules merge to form large particles.
Irreversible as film around globule is destroyed.
Leads to progressive increase in size of the dispersed phase leading to breaking.
50
What is breaking?
Complete separation of the two liquid phases.
| Irreversible as emulsifying films have been destroyed.
51
What is a semi-solid dosage form?
A body of product which when applied to the skin or other mucous membrane, alleviates or treats a pathological condition or other protection against a harmful environment
52
Ideal physical properties of a semi-solid dosage form?
```
Smooth texture
Elegant appearance
Non-dehydrating
Non-gritty
Non-greasy
Non-staining
Non-hygroscopic (doesn't absorb moisture from the air)
```
53
Ideal physiological properties of a semi-solid dosage form?
Non-irritating
Doesn't alter membrane function
Miscible with skin secretions
54
Ideal application properties of a semi-solid dosage form?
Easily applicable with efficient drug release
| High aqueous washability
55
Ointment definition?
Homogenous, translucent, viscous semi-solid preparations for topical use. Can be medicated or non-medicated
56
Types of bases?
Oleaginous
Absorption
Water-removable
Water-soluble
57
How can ointments be prepared?
Incorporation
| Fusion
58
Compendial requirements for ointments?
Microbial content
Minimum fill
Packaging, storage and labelling
Additional standards
59
Creams definition?
Viscous, semi-solid emulsion with an opaque appearance as contrasted with translucent ointments. Can be water in oil or oil in water
60
What does cream consistency depend on?
Where it is water in oil or oil in water
61
What type of emulsifying agent does a water in oil cream contain?
Lipophilic
62
What type of emulsifying agent does a oil in water cream contain?
Oil in water
63
Main use of water in oil creams?
Emollient or cleansing agent
64
Main use of oil in water creams?
Elegant drug delivery systems
65
Features of pastes?
Contain a high percentage (>50%) of insoluble solid
66
How are pastes prepared?
Incorporating solids directly into a congealed system by levigation with a portion of base to form a paste-like mass
67
Advantages of pastes?
Good adhesion on skin
| Less greasy
68
What are gels?
Semi-solid systems in which the liquid phase is constrained with a 3-D polymeric matrix having a high degree of physical or chemical cross-linking. Has a liquid network enclosed by the gel.
69
Uses of gels?
Lubricants
Medication
Carrier for spermicidal agents
70
Types of gel-phase?
Single-phase
| Two-phase (domain)
71
What is a single-phase gel phase?
Gels in which macromolecules are uniformly distributed throughout a liquid with no apparent boundaries between the dispersed macromolecules and the liquid. Usually organic
72
What is a two-phase (domain) gel phase?
When the gel mass consists of floccules of small distinct particles. Usually inorganic
73
What do gels contain?
```
Gelling agent
Water
Cosolvents
Preservatives
Stabilisers
```
74
Types of gel?
```
Hydrogels
Organic gels
Carbomer gels
Methylcellulose gels
Starch glycerite
Aluminium hydroxide gels
```
75
How are gels formed?
Gelation
76
What is gelation?
The gelation process mainly involves the polymerisation of monomers to form a 3D hydrogel, as well as other reactions, including cross-linking and catalysis.
77
Ingredients needed for semi-solid dosage forms?
```
APIs
Bases
Preservatives
Humectants
Antioxidants
Emulsifiers
Gelling agents
Buffers
```
78
What are bases?
Act as carriers of the medicine
| Control the extent of absorption
79
Ideal properties of bases?
Compatible with skin pH and drug
Inert, non-irritating and non-sensitising
Good solvent and/emulsifying agent
Emollient, protective, non-greasy
Easily removable
Release drug easily at site of administration
Good stability
80
Examples of oleaginous bases?
Hydrocarbons
Animal fats/ vegetable oils
Synthetic esters
81
Examples of absorption bases?
Hydrophilic petrolatum
Aquaphor
Aquabase
82
Examples of water in oil emulsion bases?
Cold cream
| Lanolin
83
Examples of oil in water emulsion bases?
Hydrophilic ointment
| Velvachol
84
Examples of water soluble bases?
Polyethene glycol ointment
Biozynme ointment
Veegum
85
Purposes of preservatives?
To prevent microbes
86
Examples of preservatives?
```
Methyl hydroxyl benzoate
Propyl hydroxyl benzoate
Chorocresol
Benzoic acid
Phenyl mercuric nitrate
```
87
Purpose of antioxidants?
To prevent free radical damage from oxygen
88
Types of antioxidants?
Antioxigens
Reducing agents
Antioxidant synergists
89
How do antioxigens work?
Reacting with free radicals. User for oil systems.
90
Examples of antioxigens?
Butylated hydroxy anisole (BHA)
| Butylated hydroxy tocopherols (BHT)
91
How do reducing agents work?
Have a lower redox potential than the drug, so they get oxidised first. Used for aqueous systems.
92
Examples of reducing agents?
Ascorbic acid
Potassium and sodium metabisulphite
Thiosulphite
93
How do antioxidant synergists work?
They are chelating or sequestering agents that enhance the effect of antioxidants
94
Examples of antioxidant synergists?
Citric acid
Tartaric acid
Lecithin
95
What are humectants?
Hydrophilic ingredients that draw moisture into the stratum corneum. It has several hydrophilic groups, mainly hydroxyl groups.
96
Uses of humectants?
Increase solubility of active ingredients
| Hydration of skin
97
What are gelling agents?
Form a gel dissolved in a liquid phase as a colloid mixture that forms a weakly cohesive internal structure,
98
Examples of gelling agents?
```
Tragacanth
Sodium alginate
Pectin
Gelatin
Cellulose derivatives
```
99
Purpose of buffers?
Compatibility with skin
Drug solubility
Drug stability
Influence on ionisation of drug
100
Examples of buffers?
Sodium acetate
Sodium citrate
Potassium meta phosphate
101
Processes of preparing semi-solids?
Trituration method
Fusion method
Chemical reaction method
Emulsification method
102
What is the trituration method used for?
Ointments
Creams
Pastes
Gels
103
What is the fusion method used for?
Ointments
Creams
Pastes
104
What is the chemical reaction method used for?
Ointments
| Creams
105
What is the enulsification method used for?
ointments
| Creams
106
Trituration definition?
The process of fragmenting a solid material
107
Levigation definition?
Process of decreasing the particle size of powders with a small amount of liquid they are insoluble to
108
Trituration process?
1) Levigation
2) mix with base
3) trituration
4) mix base to produce final weight
5) homogenisation
6) filling
109
Fusion method process?
1) grate waxy base
2) melt using a water bath
3) melt base together
4) dissolve oil soluble drug
4) add small volume phase in large volume phase
5) cooling
6) soft mass of 40°c
7) homogenisation
8) filling
110
How to prepare oil and aqueous phases?
1) oil components melted and mixed
2) oil phase then strained together through several layers of cheesecloth to remove foreign matter
3) transferred to emulsion mixing kettle
4) aqueous phase components added to purified water and filtered (can add drug at this stage if soluble)
5) phases mixed together at 70-72°c
111
Equipment used for mixing phases?
Agitator mixers
| Shear mixers
112
Advantages of agitator mixers?
Creates minimum dead space during mixing
| Used for wet granulation process
113
Disadvantages of agitator mixers?
Works at a fixed speed
114
Advantages of shear mixers?
It can be used for sterile production
115
Disadvantages of shear mixers?
Not for dry milling
| Heat generated
116
What to consider when storing semisolids before packaging?
Reaction with storage container, so best to use stainless steel
Evaporation of water, so place a non-reactive plastic sheeting in direct contact and cover the storage container with a tight-fitting stainless steel lid
117
Considerations for packaging of semi solids?
Must be able to resist shear stress of the transfer
Do not deviate from the formal process
Packaging equipment must be sanitised and flushed with a sterilant
Water and swap samples should be taken to verify microbial elimination
118
What is surface tension?
The tension of the surface film of a liquid caused by the attraction of the particles in the surface layer by the bulk of the liquid, which tends to minimise surface area.
119
The larger the surface of the liquid...
the more molecules have excessive potential energy
120
What is adsorption?
The accumulation at an interface
121
Why is adsorption important in pharmacy?
```
Taste-masking of bitter drugs
Changing solubility of drugs
Detoxification
Drug delivery formulations
Waste management
```
122
What are the two types of absorption?
```
Physical adsorption (physisorption)
Chemical adsorption (chemisorption)
```
123
What is physical adsorption?
A reversible process in which the adsorbate is bound to the surface by weak Van der Waals forces
124
What is chemical adsorption?
The molecule attaches to the surface by strong covalent bonds; meaning the molecule is modified (bonds broken and made)
125
Which type of adsorption is more specific?
Chemisorption
126
How to measure adsorption?
A known mass of adsorbent added to the solution
Shaken until no further change in concentration of the solution (concentration can be determined by chemical/radiochemical analysis, colourimetry, etc.)
What is not in the solution must therefore be adsorbed to the surface of the container
127
What is an apparent adsorption isotherm?
Shows the amount of solute adsorbed at a given temperature, per unit mass of adsorbent, plotted against equilibrium concentration
128
Two types of adsortion? (layers)
Monolayer
| Multilayer
129
Chemisorption is usually.....layer?
Mono
130
How to tell if multilayer adsorption has taken place?
The shape of the adsorption isotherm and from the impossibility small areas per adsorbed molecule calculated on the basis of monolayer adsorption
131
What is the Langmuir equation used for?
Describe adsorption from dilute solutions
132
Assumptions of the Langmuir equation?
1) all adsorption sites are energetically identical
2) only monolayer adsorption occurs
3) adsorption is localised, no lateral interactions between adsorbed molecules
133
Alternative adsorption isotherm equation?
Gibbs
134
On a Langmuir equation graph which kind of slope shows the best adsorption?
Smaller
135
What factors can affect adsorption?
```
Solute concentration
Temperature
pH
Surface area
Solubility of solute
```
136
How does solute concentration affect adsorption?
Increased solute concentration will increase the amount of adsorption occurring at equilibrium until a limiting value is reached
137
How does temperature affect adsorption?
The process is usually exothermic; therefore, an increase in temperature will decrease adsorption.
138
How does pH affect adsorption?
Influence the rate of ionisation of the solute, so the effect is dependent on the species that is more strongly adsorbed
139
How does surface area effect adsorption?
An increase in surface area will increase the extent of adsorption
140
How does the solubility of the solute affect adsorption?
The greater the solubility of the solute, the less likely it is to adsorb
141
Properties of drugs that are not easily adsorbed?
Highly ionised
Low molecular weight
Poorly soluble in acidic media
142
What does activated charcoal contain?
Magnesium oxide
| Tannic acid
143
How does activated charcoal work?
It is a substance that can adsorb enormous amounts of adsorbates
144
Drugs that can be adsorbed by activated charcoal?
Chlorphenamine
Colchicine
Phenytoin
Aspirin
145
Why is activated charcoal porous?
To increase the surface area for adsorption
146
What are non-Newtonian fluids?
They have a non-linear relationship between shear stress and shear rate
May have yield stress
147
What is yield stress?
A certain amount of shear stress is needed before a fluid will flow
148
What are the three types of non-newtonian fluids?
Bingham plastic flow
Pseudoplastic flow
Dilatant flow
149
What is Bingham plastic flow?
Associated with flocculated particles in concentrated suspensions that are broken down for flow to occur
Flow does not occur until the shear stress reaches yield value
150
Examples of Bingham plastics?
Mayonnaise
Butter
Typically creams
151
What is shear thinning?
Pseudoplastic flow
152
What is pseudoplastic flow?
Shear-thinning
No yield value, flow as soon as the stress applied
Non-linear
Viscosity decreases with increased shear rate
Apparent viscosity can be measured using a tangent on the curve
Long-chain molecules are randomly arranged, so they begin to align in the direction of flow
153
Examples of pseudo plastics?
Polymers is solution (not suspension)
Sodium alginate
Methylcellulose
154
What is shear thickening?
Dilatant flow
155
What is dilatant flow?
Shear thickening
Suspensions with >50% dispersed solids that exhibit an increase in resistance to flow with increased shear stress
Increase in volume when sheared
Return to original fluid state when stress removed
Each particle has a liquid lubricating coating allowing them to move past each other at low stress but at high stress there is not enough lubricant to stop solid-solid contact
Apparent viscosity increased with shear rate
156
Examples of dilatant flow?
Cornstarch and water
| Silica and PEG
157
Time-dependent behaviours of non-newtonian fluids?
Thixotropy
Antithixotropy
Rheopexy
158
What is thixotropy?
A time-dependent change in viscosity
The 3D structure breaks down on shearing and does not reform immediately upon the removal of the stress the way a pseudoplastic material would
159
Examples of thixotropy?
Ketchup
Creams
Gelatin gels
Synovial fluid
160
What is a hysteresis loop?
The up and down curve of a thixotropic system
| Demonstrate the breakdown of the material structure, and the area between the curves represents the extent
161
Real-life uses of thixotropy?
```
IM depot injections
Emulsions
Lotions
Creams
Ointments
```
162
Why is thixotropy useful in formulations?
When stored, fluid particles are in suspension (paste) and do not sediment but can be converted to a fluid to dispense a dose by shaking
This is a reversible gel-sol-gel transformation
Useful in depot injections as the stress will force it through the needle as a liquid but will then revert to a gel structure once the stress is removed, stopping excessive spread around the body, meaning the drug is a slow-release
163
What is antithixotropy?
The opposite of thixotropy
Increase in resistance to flow with increased time of shear
Different to dilatant as there is a solid content of around 1-10%
Believed to occur due to increased collision frequency of dispersed particles resulting in increased interparticle bonding over time
164
What is rheopexy?
Rare, time-dependent dilatant behaviour
Where a solid forms a gel when sheared more readily than it will at rest
Original viscosity is only restored with a delay after shear force has ceased
165
What is psychorheology?
The sensory judgement of rheological properties
| Feel, spreadability, colour, odour etc.
166
Most pharmaceutical dosage forms have what type of rheology?
Pseudoplastic (shear thinning)
167
What is heamorheology?
The study of blood flow in a vessel, with an emphasis on the behaviour of erythrocytes
168
What rheological behaviour does blood show?
Pseudoplastic (shear thinning) as slow-moving blood during diastole is stickier than fast-moving blood during systole
169
What is a creep curve?
A test to show the changes in a pharmaceutical solid, such as a cream or ointment, undergoes as it is stressed over a period of time
