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Pharmaceutics Flashcards

1
Q

What is rheology?

A

The science of flow. Describes the flow of liquids and deformation of solids.

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2
Q

Two underlying concepts of rheology?

A

1) Intermolecular forces and bonding

2) timetable of experimental observations

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3
Q

What is viscosity?

A

An expression of the resistance of a fluid to flow

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4
Q

What did Hooke define?

A

an ideal elastic solid

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5
Q

What did Newton define?

A

An ideal liquid

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6
Q

What does viscoelastic mean?

A

Having both liquid and solid character

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7
Q

Newton’s law of flow states?

A

The rate of flow is directly proportional to the applied stress

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8
Q

What is shearing stress?

A

The force per unit area to bring about flow

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9
Q

What is a Newtonian fluid?

A

Viscosity does not chance with increased shear rate, only with temperature

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10
Q

How to tell a Newtonian fluid on a graph?

A

proportional and linear

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11
Q

What is viscosity measured in?

A

poise or Pas

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12
Q

What is the Mark-Houwink equation for?

A

Determining molecular weight from viscosity

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13
Q

Types of non-newtonian fluids?

A

Shear-thinning (pseudoplastic)
Shear-thickening (dilatant)
Bingham (plastic)

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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.

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15
Q

What types of emulsions are there?

A

Oil-in-water
Water-in-oil
Double emulsions

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16
Q

What is the most common type of emulsion?

A

Oil-in-water

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17
Q

What are oil-in-water emulsions used for?

A

Oral
Injectable
Ophthalmic
Topical

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18
Q

Oil-in-water emulsions require what kind of emulsifying agent?

A

Hydrophilic

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19
Q

Examples of hydrophilic emulsifying agents?

A

Sodium lauryl sulfate
Triethanolamine sterate
Sodium oleate
Glyceryl monostearate

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20
Q

What are water-in-oil emulsions used for?

A

Mainly topical application

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21
Q

Water-in-oil emulsions require what kind of emulsifying agent?

A

Lipophilic

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22
Q

Examples of lipophilic emulsifying agents?

A

Calcium palmitate
Sorbitan esters
Cholesterol
Wool fats

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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

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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

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25
Q

What are the three emulsion theories?

A

Surface tension theory
Interfacial film theory
Monomolecular adsorption/ orientated-wedge theory

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26
Q

What is surface tension theory?

A

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

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27
Q

What is interfacial film theory?

A

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

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28
Q

The main difference between surface tension theory and interfacial film theory?

A

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

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29
Q

What is orientated-wedge theory?

A

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

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30
Q

Why are there different emulsification theories?

A

Because of the different types of emulsifiers

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31
Q

What are the three main groups of emulsifiers?

A

Surface active agents (surfactants)
Hydrophilic colloids
Finely divided solid particles

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32
Q

How do surfactant emulsifiers work?

A

Adsorbed at the oil-water interface to form a monomolecular film and reduce interfacial tension

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33
Q

How do hydrophilic colloids work as emulsifiers?

A

Form a multimolecular film around the dispersed globules of an oil-in-water emulsion

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34
Q

How do finely divided solid particles work as emulsifiers?

A

Adsorbed around dispersed globules

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35
Q

What is the most common type of emulsifiers?

A

Surfactants

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36
Q

What does surfactant stand for?

A

Surface-active agents

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37
Q

What is a key property that determines the type of an emulsifier?

A

Hydrophilic-lipophilic balance (HLB) value

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38
Q

What HLB value is needed for an oil-in-water emulsifier?

A

9-12

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39
Q

What HLB value is needed for a water-in-oil emulsifier?

A

3-6

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40
Q

What is the Bancroft rule?

A

The phase in which an emulsifier is more soluble constitutes the continuous phase

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41
Q

How are emulsions made?

A

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

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42
Q

What can go wrong with emulsions?

A

Stability issues
Chemical instabilities
Microbial issues

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43
Q

What is creaming?

A

The upward movement of less dense dispersed oil globules in an oil-in-water emulsion.
Visually evident with separation of layers.
Reversible by shaking

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44
Q

What is sedimentation?

A

The downward movement of more dense dispersed water globules in a water-in-oil emulsion.
Visually evident with separation of layers.
Reversible by shaking

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45
Q

What is the difference between creaming and sedimentation?

A

Creaming occurs in oil-in-water emulsions whereas sedimentation occurs in water-in-oil emulsions

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46
Q

What is Stoke’s law?

A

models creaming and sedimentation in an emulsion. Can be used to enhance physical stability of emulsions

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47
Q

How to enhance the stability of an emulsion?

A

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

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48
Q

What is aggregation/flocculation?

A

It involves the close packing of the dispersed phase, but the globules do not fuse.
It is reversible to an extent.

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49
Q

What is coalescence?

A

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.

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50
Q

What is breaking?

A

Complete separation of the two liquid phases.

Irreversible as emulsifying films have been destroyed.

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51
Q

What is a semi-solid dosage form?

A

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

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52
Q

Ideal physical properties of a semi-solid dosage form?

A 
Smooth texture
Elegant appearance
Non-dehydrating
Non-gritty
Non-greasy
Non-staining
Non-hygroscopic (doesn't absorb moisture from the air)
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53
Q

Ideal physiological properties of a semi-solid dosage form?

A

Non-irritating
Doesn’t alter membrane function
Miscible with skin secretions

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54
Q

Ideal application properties of a semi-solid dosage form?

A

Easily applicable with efficient drug release

High aqueous washability

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55
Q

Ointment definition?

A

Homogenous, translucent, viscous semi-solid preparations for topical use. Can be medicated or non-medicated

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56
Q

Types of bases?

A

Oleaginous
Absorption
Water-removable
Water-soluble

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57
Q

How can ointments be prepared?

A

Incorporation

Fusion

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58
Q

Compendial requirements for ointments?

A

Microbial content
Minimum fill
Packaging, storage and labelling
Additional standards

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59
Q

Creams definition?

A

Viscous, semi-solid emulsion with an opaque appearance as contrasted with translucent ointments. Can be water in oil or oil in water

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60
Q

What does cream consistency depend on?

A

Where it is water in oil or oil in water

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61
Q

What type of emulsifying agent does a water in oil cream contain?

A

Lipophilic

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62
Q

What type of emulsifying agent does a oil in water cream contain?

A

Oil in water

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63
Q

Main use of water in oil creams?

A

Emollient or cleansing agent

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64
Q

Main use of oil in water creams?

A

Elegant drug delivery systems

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65
Q

Features of pastes?

A

Contain a high percentage (>50%) of insoluble solid

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66
Q

How are pastes prepared?

A

Incorporating solids directly into a congealed system by levigation with a portion of base to form a paste-like mass

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67
Q

Advantages of pastes?

A

Good adhesion on skin

Less greasy

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68
Q

What are gels?

A

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
Q

Uses of gels?

A

Lubricants
Medication
Carrier for spermicidal agents

70
Q

Types of gel-phase?

A

Single-phase

Two-phase (domain)

71
Q

What is a single-phase gel phase?

A

Gels in which macromolecules are uniformly distributed throughout a liquid with no apparent boundaries between the dispersed macromolecules and the liquid. Usually organic

72
Q

What is a two-phase (domain) gel phase?

A

When the gel mass consists of floccules of small distinct particles. Usually inorganic

73
Q

What do gels contain?

A 
Gelling agent
Water
Cosolvents
Preservatives
Stabilisers
74
Q

Types of gel?

A 
Hydrogels
Organic gels
Carbomer gels
Methylcellulose gels
Starch glycerite
Aluminium hydroxide gels
75
Q

How are gels formed?

A

Gelation

76
Q

What is gelation?

A

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
Q

Ingredients needed for semi-solid dosage forms?

A 
APIs
Bases
Preservatives
Humectants
Antioxidants
Emulsifiers
Gelling agents
Buffers
78
Q

What are bases?

A

Act as carriers of the medicine

Control the extent of absorption

79
Q

Ideal properties of bases?

A

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
Q

Examples of oleaginous bases?

A

Hydrocarbons
Animal fats/ vegetable oils
Synthetic esters

81
Q

Examples of absorption bases?

A

Hydrophilic petrolatum
Aquaphor
Aquabase

82
Q

Examples of water in oil emulsion bases?

A

Cold cream

Lanolin

83
Q

Examples of oil in water emulsion bases?

A

Hydrophilic ointment

Velvachol

84
Q

Examples of water soluble bases?

A

Polyethene glycol ointment
Biozynme ointment
Veegum

85
Q

Purposes of preservatives?

A

To prevent microbes

86
Q

Examples of preservatives?

A 
Methyl hydroxyl benzoate
Propyl hydroxyl benzoate
Chorocresol
Benzoic acid
Phenyl mercuric nitrate
87
Q

Purpose of antioxidants?

A

To prevent free radical damage from oxygen

88
Q

Types of antioxidants?

A

Antioxigens
Reducing agents
Antioxidant synergists

89
Q

How do antioxigens work?

A

Reacting with free radicals. User for oil systems.

90
Q

Examples of antioxigens?

A

Butylated hydroxy anisole (BHA)

Butylated hydroxy tocopherols (BHT)

91
Q

How do reducing agents work?

A

Have a lower redox potential than the drug, so they get oxidised first. Used for aqueous systems.

92
Q

Examples of reducing agents?

A

Ascorbic acid
Potassium and sodium metabisulphite
Thiosulphite

93
Q

How do antioxidant synergists work?

A

They are chelating or sequestering agents that enhance the effect of antioxidants

94
Q

Examples of antioxidant synergists?

A

Citric acid
Tartaric acid
Lecithin

95
Q

What are humectants?

A

Hydrophilic ingredients that draw moisture into the stratum corneum. It has several hydrophilic groups, mainly hydroxyl groups.

96
Q

Uses of humectants?

A

Increase solubility of active ingredients

Hydration of skin

97
Q

What are gelling agents?

A

Form a gel dissolved in a liquid phase as a colloid mixture that forms a weakly cohesive internal structure,

98
Q

Examples of gelling agents?

A 
Tragacanth
Sodium alginate
Pectin
Gelatin
Cellulose derivatives
99
Q

Purpose of buffers?

A

Compatibility with skin
Drug solubility
Drug stability
Influence on ionisation of drug

100
Q

Examples of buffers?

A

Sodium acetate
Sodium citrate
Potassium meta phosphate

101
Q

Processes of preparing semi-solids?

A

Trituration method
Fusion method
Chemical reaction method
Emulsification method

102
Q

What is the trituration method used for?

A

Ointments
Creams
Pastes
Gels

103
Q

What is the fusion method used for?

A

Ointments
Creams
Pastes

104
Q

What is the chemical reaction method used for?

A

Ointments

Creams

105
Q

What is the enulsification method used for?

A

ointments

Creams

106
Q

Trituration definition?

A

The process of fragmenting a solid material

107
Q

Levigation definition?

A

Process of decreasing the particle size of powders with a small amount of liquid they are insoluble to

108
Q

Trituration process?

A

1) Levigation
2) mix with base
3) trituration
4) mix base to produce final weight
5) homogenisation
6) filling

109
Q

Fusion method process?

A

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
Q

How to prepare oil and aqueous phases?

A

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
Q

Equipment used for mixing phases?

A

Agitator mixers

Shear mixers

112
Q

Advantages of agitator mixers?

A

Creates minimum dead space during mixing

Used for wet granulation process

113
Q

Disadvantages of agitator mixers?

A

Works at a fixed speed

114
Q

Advantages of shear mixers?

A

It can be used for sterile production

115
Q

Disadvantages of shear mixers?

A

Not for dry milling

Heat generated

116
Q

What to consider when storing semisolids before packaging?

A

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
Q

Considerations for packaging of semi solids?

A

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
Q

What is surface tension?

A

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
Q

The larger the surface of the liquid…

A

the more molecules have excessive potential energy

120
Q

What is adsorption?

A

The accumulation at an interface

121
Q

Why is adsorption important in pharmacy?

A 
Taste-masking of bitter drugs
Changing solubility of drugs
Detoxification
Drug delivery formulations
Waste management
122
Q

What are the two types of absorption?

A 
Physical adsorption (physisorption) 
Chemical adsorption (chemisorption)
123
Q

What is physical adsorption?

A

A reversible process in which the adsorbate is bound to the surface by weak Van der Waals forces

124
Q

What is chemical adsorption?

A

The molecule attaches to the surface by strong covalent bonds; meaning the molecule is modified (bonds broken and made)

125
Q

Which type of adsorption is more specific?

A

Chemisorption

126
Q

How to measure adsorption?

A

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
Q

What is an apparent adsorption isotherm?

A

Shows the amount of solute adsorbed at a given temperature, per unit mass of adsorbent, plotted against equilibrium concentration

128
Q

Two types of adsortion? (layers)

A

Monolayer

Multilayer

129
Q

Chemisorption is usually…..layer?

A

Mono

130
Q

How to tell if multilayer adsorption has taken place?

A

The shape of the adsorption isotherm and from the impossibility small areas per adsorbed molecule calculated on the basis of monolayer adsorption

131
Q

What is the Langmuir equation used for?

A

Describe adsorption from dilute solutions

132
Q

Assumptions of the Langmuir equation?

A

1) all adsorption sites are energetically identical
2) only monolayer adsorption occurs
3) adsorption is localised, no lateral interactions between adsorbed molecules

133
Q

Alternative adsorption isotherm equation?

A

Gibbs

134
Q

On a Langmuir equation graph which kind of slope shows the best adsorption?

A

Smaller

135
Q

What factors can affect adsorption?

A 
Solute concentration 
Temperature 
pH
Surface area
Solubility of solute
136
Q

How does solute concentration affect adsorption?

A

Increased solute concentration will increase the amount of adsorption occurring at equilibrium until a limiting value is reached

137
Q

How does temperature affect adsorption?

A

The process is usually exothermic; therefore, an increase in temperature will decrease adsorption.

138
Q

How does pH affect adsorption?

A

Influence the rate of ionisation of the solute, so the effect is dependent on the species that is more strongly adsorbed

139
Q

How does surface area effect adsorption?

A

An increase in surface area will increase the extent of adsorption

140
Q

How does the solubility of the solute affect adsorption?

A

The greater the solubility of the solute, the less likely it is to adsorb

141
Q

Properties of drugs that are not easily adsorbed?

A

Highly ionised
Low molecular weight
Poorly soluble in acidic media

142
Q

What does activated charcoal contain?

A

Magnesium oxide

Tannic acid

143
Q

How does activated charcoal work?

A

It is a substance that can adsorb enormous amounts of adsorbates

144
Q

Drugs that can be adsorbed by activated charcoal?

A

Chlorphenamine
Colchicine
Phenytoin
Aspirin

145
Q

Why is activated charcoal porous?

A

To increase the surface area for adsorption

146
Q

What are non-Newtonian fluids?

A

They have a non-linear relationship between shear stress and shear rate
May have yield stress

147
Q

What is yield stress?

A

A certain amount of shear stress is needed before a fluid will flow

148
Q

What are the three types of non-newtonian fluids?

A

Bingham plastic flow
Pseudoplastic flow
Dilatant flow

149
Q

What is Bingham plastic flow?

A

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
Q

Examples of Bingham plastics?

A

Mayonnaise
Butter
Typically creams

151
Q

What is shear thinning?

A

Pseudoplastic flow

152
Q

What is pseudoplastic flow?

A

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
Q

Examples of pseudo plastics?

A

Polymers is solution (not suspension)
Sodium alginate
Methylcellulose

154
Q

What is shear thickening?

A

Dilatant flow

155
Q

What is dilatant flow?

A

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
Q

Examples of dilatant flow?

A

Cornstarch and water

Silica and PEG

157
Q

Time-dependent behaviours of non-newtonian fluids?

A

Thixotropy
Antithixotropy
Rheopexy

158
Q

What is thixotropy?

A

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
Q

Examples of thixotropy?

A

Ketchup
Creams
Gelatin gels
Synovial fluid

160
Q

What is a hysteresis loop?

A

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
Q

Real-life uses of thixotropy?

A 
IM depot injections 
Emulsions
Lotions
Creams
Ointments
162
Q

Why is thixotropy useful in formulations?

A

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
Q

What is antithixotropy?

A

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
Q

What is rheopexy?

A

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
Q

What is psychorheology?

A

The sensory judgement of rheological properties

Feel, spreadability, colour, odour etc.

166
Q

Most pharmaceutical dosage forms have what type of rheology?

A

Pseudoplastic (shear thinning)

167
Q

What is heamorheology?

A

The study of blood flow in a vessel, with an emphasis on the behaviour of erythrocytes

168
Q

What rheological behaviour does blood show?

A

Pseudoplastic (shear thinning) as slow-moving blood during diastole is stickier than fast-moving blood during systole

169
Q

What is a creep curve?

A

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

Mpharm (9 decks)

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