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Pharmacy Year 2 Semester 2 > Methods Of Formulation > Flashcards

Methods Of Formulation Flashcards

1
Q

What are dispersions?

A

Unlike solutions, dispersions are a suspension of one type of particle in a continuous phase but they don’t dissolve, they are just suspended there.
E.g. Particles of gas or liquid or air, solid particles or droplets in another component

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2
Q

What are disperse systems made up of? What are they?

A

Made up of disperse phase - particles or droplets

Which is dispersed in another component known as the continuous phase

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3
Q

Describe the difference between colloidal dispersions and coarse dispersions

A

Colloidal dispersion particle size 1nm-1um diameter
To be classified as colloid, the particles must NOT settle under gravity

Coarse dispersion particle size >1um

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4
Q

What is a sol? Give an example

A

A sol is a colloidal dispersion of solid in a liquid

E.g. Jelly

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5
Q

What is an emulsion? Give an example

A

An emulsion is a mixture of two liquids

E.g. Mayonnaise or milk

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6
Q

What is a foam? Give an example

A

A foam is when many gas particles are trapped in a liquid or a solid
Gas in liquid - e.g. Frothy coffee
Gas in solid - e.g. Meringues

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7
Q

What is an aerosol?

A

An aerosol contains small particles of liquid or solid dispersed in a gas

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8
Q

How to know the difference between a solution and a sol?

A

If it dissolves, it is a solution.

If it does not, it is a sol.

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9
Q

What do lyophobic and lyophilic mean?

A

Lyophilic - solvent-loving
Lyophobic - solvent-hating
Lyo- = solvent
The terms hydrophilic and hydrophobic are used when water is the solvent

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10
Q

Describe some features of lyophilic sols

A

Lyophilic sols…

  • exhibit high visocity
  • contain asymmetrical particles
  • are stable in the presence of electrolytes
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11
Q

Name types of molecules whereby lyophilic sols are formed

A

Lyophilic sols are formed by:

  • surfactant molecules forming micelles in water
  • proteins and gums in suspension, e.g. Acacia and methylcellulose
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12
Q

Describe features of lyophobic sols

A

Lyophobic sols:

  • exhibit low viscosity
  • contain symmetrical particles
  • are very sensitive to the addition of electrolytes , which causes irreversible aggregation
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13
Q

How are lyophobic sols formed? Give an example

A

Lyophobic sols are formed by dispersions of oil and water

E.g. Milk, mayonnaise

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14
Q

How would you make a lyophilic colloid?

A

The affinity of lyophilic colloids for their dispersion medium leads to spontaneous formation of colloidal dispersion
I.e.
Just mix them!

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15
Q

How would you make a lyophobic colloid? Name the two main ways

A

Lyophobic colloid systems are prepared by dispersion or condensation

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16
Q

What does dispersion of material to form a colloid involve?

A

Dispersion involves breakdown of coarse material by colloid mills or ultrasonic treatment

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17
Q

What does condensation of a material to form a colloid involve?

A

Condensation involves the rapid production of a supersaturated solution of the colloidal material under conditions that cause formation of colloidal particles and not a precipitate.

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18
Q

Give an example of how condensation can form colloids

What else can form colloidal sol particles?

A

Silver iodide + potassium iodide–> colloidal silver iodide

a change in solvent can induce formation of colloidal sol particles
E.g.
When a saturated solution of sulphur in acetone is poured slowly into hot water, the acetone vaporises and leaves a colloidal dispersion of sulphur

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19
Q

Name 3 ways of purifying colloidal systems

A

Dialysis
Ultrafiltration
Electrodialysis

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20
Q

What does normal dialysis of particles involve?

A

Purifies colloidal systems
Colloidal particles are too large to diffuse through man-made membranes such as cellophane or collodion or man-made cassettes
Particles are separated and purified by dialysis against a large volume of liquid using these man-made membranes

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21
Q

What does ultrafiltration of particles involve?

A

Method for purifying colloidal sol particles
By applying pressure (or suction), solvent molecules and impurities can be forced across a membrane
But colloidal particles are retained
This method is faster than dialysis

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22
Q

What is the size range of colloidal particles like? How is it quantified?

A

The size range is often very wide, so the size/molecular weight is given as an average value

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23
Q

Shape of colloidal particles

A

Normally spherical but also:

  • oblate ellipsoids (discus-shaped)
  • prolate ellipsoids (rugby ball-shaped)
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24
Q

What kind of movement do colloidal particles undergo?

A

Colloidal particles are subject to brownian motion - random collisions leading to a zig-zag motion - with molecules of the dispersion medium
As a result of this motion, colloidal particles are able to spontaneously diffuse from regions of high concentration to regions of low concentration

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25
Q

At what size will the colloidal particles sediment under gravity? What is another way of sedimenting them if they are not this size?

A

Particles will sediment under gravity at a size of 0.5um or greater
Below this, particles will have to be sedimented by centrifugation (manually)

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26
Q

What does electrodialysis/electrodecantation of particles involve?

A

An electrical potential can be applied to increase the rate of movement of ionic impurities across a dialysis membrane, speeding up purification.
This process is called electrodecantation

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27
Q

What is aggregation of particles? When does it occur?

A

Permanent contact between particles
Caused by frequent collisions
As large aggregates form, they sediment out of solution

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28
Q

What is coagulation?

A

Coagulation describes particles that are closely aggregated and difficult to disperse

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29
Q

What is flocculation?

A

Flocculation describes aggregates with an open structure

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30
Q

Describe the 3 main groups of forces between particles in colloidal systems that cause flocculation, aggregation, coagulation etc

A

-electrical forces of repulsion due to the charge on each particle - stay in stable form/system

  • forces of attraction (van der Waals forces of attraction)
  • forces arising from solvation (flocculation and coagulation)
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31
Q

How can we use the aggregation of colloidal sol particles to our own advantage?

A

In the formation of gels

The majority of gels are formed by aggregation of colloidal sol particles

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32
Q

By weight gels are mostly liquid, but they behave like solids. Why is this?

A

This is due to a 3-dimensional cross-linked network within the liquid
The solid or semi-solid form is composed of inter-linked particles
The particle network imparts rigidity to the structure

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33
Q

A gel rich is liquid is called…

A

A jelly

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34
Q

A gel that contains no liquid is called a…

Give exmaples

A

Xerogel

E.g. Sheet gelatin, tragacanth flakes

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35
Q

Name some gels from lyophobic sols and describe their composition

A 
Clays e.g:
Bentonite
Aluminium magnesium silicate 
Kaolin 
Are composed of charged particles and form gels by flocculation, but in a different way
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36
Q

Describe the structure of lyophobic sols

A

The face of the particle has a negative charge and the edge of the particle has a positive charge
Due to the electrostatic interactions between the faces and edges of different particles, a gel structure builds up in a ‘card house’ floc

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37
Q

Describe the forces in a card house floc

A

The forces holding the particles together are relatively weak, allowing gels to exhibit thixotropy - a non-chemical, isothermal [doesn’t need heat] gel to sol to gel transformation

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38
Q

Describe how gels from lyophobic sols exhibit thixotropy

A

Simple shaking breaks these bonds and the gel turns into a sol
Upon standing the particles collide, flocculate and the gel is reformed
This phenomenon is observed in calamine lotion

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39
Q

How are gels from lyophilic sols divided?

A

Type I and Type II gels

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40
Q

What is a type I gel from a lyophilic sol? Give an example

A

Type I gels are irreversible systems formed from a 3D network of covalent bonds, e.g. Polymers of water-soluble monomers formed with a cross-linking agent
E.g. Poly(HEMA) cross-linked with EGDMA

41
Q

Type I gel pharmaceutical/medical uses

A

Type I gels swell in water but do not dissolve due to the stabilising crosslinks
They are implanted in a dehydrated state and swell to fill a body cavity or can be used for fabrication of sustained release dosage forms

42
Q

Describe Type II gels formed from lyophilic sols

A

Type II gels are held together by weaker bonds (e.g. Hydrogen bonds) and are therefore heat reversible, with transition from sol to gel occurring on heating or cooling

43
Q

Medical/pharmaceutical applications of type II gels

A

-Poly(vinyl alcohol) solutions gel on cooling and are used as jellies for application of drugs to the skin, leaving a plastic film on the skin

-concentrated solutions of poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block co-polymers
E.g. Pluronic surfactant forms a gel on heating

44
Q

What aggregates do type II gels form?

A

These molecules form micelles and their solubility decreases with increased temperature
Upon warming, more and more micelles form. If the solution is concentrated, gelation occurs.
Micelles are packed so closely together. That movement is prevented as a gel phase is formed

45
Q

What are surfactants? Give an example

A

Surfactants are amphipathic molecules that have both hydrophobic and hydrophilic groups
E.g. Sodium stearate

46
Q

Describe what makes surfactants surface-active

A

surfactants accumulate between the boundary of 2 phases e.g. Liquid/gas, oil/water. This reduces the surface tension.
This allows the hydrophobic region of the molecule to ‘escape’ the hostile aqueous environment

47
Q

What is CMC?

A

The critical micelle concentration
At this concentration, there is no room for any more micelles at the surface, leaving a proportion of molecules unable to escape the hydrophilic conditions
-to shield their hydrophobic groups, they form spherical aggregates called micelles (spontaneously)

48
Q

With increasing lengths of hydrophobic chains on surfactants, what happens to the CMC?

A

CMC decreases with increasing lengths of hydrophobic chains as it takes up more space on the surface

49
Q

Name 4 types of micelle and describe their basic structure

A
  • Non-ionic surfactants: often long chain alcohols
  • Anionic surfactants: contain anionic groups on their head
  • Cationic surfactants: contain cationic groups on their head
  • Zwitterionic (amphoteric) surfactants: have both cationic and anionic centres attache to the same head molecule
50
Q

Examples of non-ionic surfactants

A 
Often long chain alcohols 
E.g: 
-cetyl alcohol
-stearyl alcohol
-cetostearyl alcohol (e.g. Triton X-100, Nonoxynol-9)
51
Q

Examples of anionic surfactants

A

Contain anionic groups on their head such as sulphate, sulphonate, phosphate and carboxylate
E.g.
-ammonium lauryl sulphate
-sodium lauryl sulphate

52
Q

Examples of cationic surfactants

A

Contain pH-dependent primary, secondary or tertiary amines, or the permanently charged quaternary ammonium cation
E.g.
-Benzalkonium chloride

53
Q

Examples of zwitterionic surfactants

A
  • CHAPS
  • phophatidylserine
  • phosphatidylcholine
54
Q

What is a micelle?

A

A micelle is an aggregate of surfactant molecules dispersed in a liquid
Oil-in-water micelle = normal phase micelle

55
Q

What is an inverse micelle?

A

A water-in-oil micelle

Oily continuous phase, so the head groups are in the centre and the fatty chains are exposed to the oil

56
Q

What are micelle shape and size determined by?

A
  • concentration and properties of the surfactant
  • temperature
  • pH
  • ionic strength
  • solubility (the more soluble the surfactant, the easier the micelles form)
57
Q

List features of a typical micelle

A
  • Spherical
  • composed of 50-100 surfactant molecules
  • ~2.5nm in diameter
58
Q

Describe how insoluble/partially soluble drugs can be solubilised by micelles

A

The hydrophobic core can dissolve non-polar molecules, so insoluble substances can be solubilised by micelles
Non-polar drug with hydrophobic tails of micelle
‘Inside’ micelles

59
Q

Name some pharmaceutical applications of micelles

A
  • disinfectants:
  • phenolic compounds (such as cresol and thymol) are frequently solubilised with surfactant to form a clear solution for disinfection. Stops them from precipitating out
  • Production of clear solutions for ophthalmic use
  • Polyoxyethylene sorbitan esters of fatty acids have also been used for preparation of aqueous injections of fat soluble vitamins (ADEK)
60
Q

Describe how micelles are used in optical formulations

A

The low solubility of steroids in water provides problems for optical use, and oil-based solutions and suspensions are optically clear (especially eye drops)

Non-ionic surfactants (e.g. Polysorbates, polyoxyethylene sorbitan esters of fatty acids) are used to produce clear solutions that are stable to sterilisation

61
Q

What is coarse disperse system?

A

A pharmaceutical suspension is a coarse dispersion of insolble particles >1um in diameter, usually dispersed in an aqueous medium

62
Q

Uses of coarse disperse systems

A
  • used for the administration of poorly soluble or insoluble drugs
  • the large surface area of the dispersed drug provides high availability for dissolution
  • suspensions can be administered via the GIT or for parenteral or ophthalmic use
63
Q

Describe the ideal characteristics of coarse disperse systems used in suspensions for ophthalmic/parenteral/GIT use

A

Ideally:

  • suspended material should not settle too quickly
  • the sediment should not aggregate and should be easily resuspended
  • viscosity should allow for pouring and/or administration through a syringe needle (needs to be able to flow)
64
Q

Major difference between pharmaceutical suspensions and colloidal systems?

A

The share most of their properties together but the major difference is that the relatively large size of particles may cause them to sediment under gravity

65
Q

What is an emulsion?

A

An emulsion consists of 2 immiscible liquids, one dispersed in the other in the form of fine droplets

66
Q

What is an emulsifying agent?

A

an agent used in emulsions, it is needed to stabilise the emulsion
It is a surfactant that lies on the oil-water interface

67
Q

What is the disperse and continuous phase in emulsions?

A

The fine droplets are the disperse phase

The phase in which the droplets are suspended is the continuous phase

68
Q

Droplet size in emulsions and their relative stability

A

0.1-100um and are inherently unstable

Droplets smaller than this are more stable and exhibit colloidal behaviour

69
Q

2 main types of emulsions

A

Oil in water (o/w)

Water in oil (w/o)

70
Q

Uses of emulsions

A
  • formulation of creams, ointments and pastes
  • administration of oils/fats for IV nutrition, using lecithin (non-toxic) as an emulsifying agent to stop problems with blood clotting that lipids introduced to the body can cause. Particle size must be controlled to prevent embolisms (make sure not blocking tiny blood vessels, e.g. In the extremities)
71
Q

When is an emulsion defined as stable?

A

If their globules retain their initial character and remain uniformly distributed throughout the continuous phase

72
Q

Emulsifying agent action

A

The emulsifying agent forms an interfacial film around dispersed droplets
The physical form of this barrier will determine whether the droplets can coalesce or not

73
Q

Separation of an emulsion is termed…

A

Cracking or breaking

74
Q

How does cracking of an emulsion occur?

A

any agent or process that destroys the interfacial film (of the emulsifying agent) will crack the emulsion:

  • chemicals incompatible with the emulsifying agent
  • bacterial growth
  • temperature change
75
Q

How does coalescence of an emulsion occur?

A

Small droplets combine to form larger ones - any electric charge on the particles will repulse this

76
Q

How does creaming of an emulsion occur?

A

Disperse phase rises to the top (or sinks to the bottom) as a result of density differences between phases.
It can be redistributed, but may result in inappropriate dosage

77
Q

How does breaking of an emulsion occur?

A

The emulsion splits back into two separate layers

78
Q

How does flocculation of an emulsion occur?

A

Droplets form clusters - the combined result of attractive and repulsive forces

79
Q

What is phase inversion (of an emulsion)?

A

Emulsions stabilised with non-ionic emulsifying agents may undergo phase inversion on heating
E.g. If an oil-in-water emulsion reverts to a water-in-oil emulsion or vice versa

80
Q

How do you increase stability of an emulsion?

A
  • reduce globule size
  • decreased density differences
  • increasing viscosity of the continuous phase (makes it more difficult for particles to move, so harder to flocculate/coalesce/separate)
81
Q

How is stability of emulsions assessed?

A
  • visualisation (with/without microscope)

- tracking particle size over time (to see if it has varied) you can see if coalescence/flocculation is occurring

82
Q

What is an aerosol?

A

An aerosol is a colloidal dispersion of liquid or solid in a gas

83
Q

What are mists and fogs?

What about smokes?

A

Mists and fogs are dispersions of liquid in gas

Smokes are dispersions of solid in gas

84
Q

Aerosol stability in comparison to colloids

A

Aerosols/mists/figs/smokes are less stable than colloids that have a liquid dispersion medium but exhibit similar properties

85
Q

Aerosol similarity to colloids

A

Particle size of aerosols is usually in the colloidal range (1um-1um)
But if the particles are bigger than 1um (coarse dispersion) the life of the aerosol is short because the particles separate out too quickly, therefore they are not manufacturable

86
Q

Uses of aerosols

A

-used for administering drug topically or locally to the respiratory system
-aerosols can be used to administer a drug systemically if drug particles are absorbed into the blood stream from the lungs - penetrate through the blood vessels in the lung
E.g. Aerosol version of insulin is being developed

87
Q

Particle size of aerosols that give:

  • good penetration into the airways
  • deposited in the mouth/throat
  • exhaled
A

1-5um are needed to achieve good penetration into airways

Particles >10um are deposited in the mouth/throat

Particles<0.5um may be exhaled

88
Q

What is a foam?

A

A foam is a coarse dispersion of a gas in a liquid

89
Q

How are foams formed?

A

Upon mixing the liquid exists as a thin interfacial film between gas bubbles.
A foam starts to form when surfactant molecules adsorb to interfaces like gas bubbles
-The hydrophilic end faces the aqueous side of the interface
-the hydrophobic end faces the non-aqueous side

90
Q

What happens if you have a foam without surfactant?

A

The gas would settle out
Water will separate out due to gravity
Gas bubbles will start to fuse and burst

91
Q

What keeps a foam able to be relatively stable?

A

The interfacial cavity of surfactant molecules inhibits gas to liquid mass transfer and stabilises the foam
It also:
-increases its flexibility
-inhibits bulk liquid drainage
-prevents bubbles from popping due to protective interfacial layer

92
Q

Foams are unstable. Why?

A

Due to the tendency of the liquid film to drain and thin, or rupture
Rupture may be caused by vibration, heat and diffusion of gas from small bubbles to large bubbles, which slowly destabilises the foam

93
Q

Pharmaceutical uses of foams

A

Foams deliver a range of agents, including:
-sun-screen
-corticosteroids
-antibacterial, anti-fungal, antiviral agents
They are also used for:
-rectal, vaginal and topical delivery
-burn dressings

94
Q

What are foam breakers? How do the act?

A

Highly surface-active
Act by lowering the surface tension over small areas of the liquid film e.g. Ether and n-octanol
These regions are stretched out by surrounding regions of higher tension, leaving small areas thinned and prone to rupture

95
Q

What are foam breakers used for pharmaceutically?

A

Dyspepsia
Flatulence
Gas in stomach
-all caused by foams (gas trapped) and so foam breakers can treat these conditions

96
Q

What are foam inhibitors?

A

They are agents that prevent foams from forming

97
Q

How do foam inhibitors work? Give an example of one.

A

They adsorb at the air/water interface in preference to the foaming agent, but do not have the ability to form a stable foam
E.g. Silicones
They have low interfacial tension and rapidly adsorb to, and disrupt the foam

98
Q

Medical uses of foam inhibitors

A

Silicones used for:

  • treatment of flatulence (farting)
  • removal of GI gases prior to radiography
  • treatment of dyspepsia

Pharmacy Year 2 Semester 2 (33 decks)

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