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The Medicine 20100 > Methods Of Formulation I > Flashcards

Methods Of Formulation I Flashcards

1
Q

What is a disperse system

A

A system made of a dispersed/internal phase (particles or droplets) dispersed in another component (the continuous phase)

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2
Q 
Define:
Colloidal dispersion
Coarse dispersion
Sol
Emulsion
Foam
Aerosol
A

A term used when the droplets are between 1nm-1micrometer
A term used when the droplets are above 1micrometer in size. Often relates to emulsions and suspensions
A colloidal dispersion of solid particles in a liquid
A mixture of two immiscible liquids
When gas particles are trapped in a liquid or a solid
A solid or liquid dispersed in a gas

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3
Q

Detail the characteristics of a lyophobic sol
(A colloid that is solvent hating)

Include details of the effect of electrolytes, stability, formation, viscosity

A

These colloids are very sensitive to electrolytes leading to irreversible aggregation. Depends on the type and valency of counter ion and the concentration of the electrolyte

Stability is controlled by the charge of the particles

They are usually made of metals, inorganic crystals. Are never formed spontaneously. Particles remain dispersed fur to electric repulsion

Low viscosity, particles unsolvated and usually symmetric

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4
Q

Detail some characteristics of a lyophilic sol

A

Solvation plays an important role in stability. Generally stable in the presence of electrolytes except when the electrolytes are at high concentrations (desolation of lyophilic molecule). Proteins more sensitive at the pI

Stability is controlled by the charge and salvation of particles

Are usually formed of proteins, macromolecules (which disperse spontaneously in the solvent). Free energy of formation is negative - they have a stable thermodynamic system hence they can firm spontaneously.

Usually have a high viscosity (when the concentration is high in some cases a gel can form). Particles are solvated and usually asymmetric.

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5
Q

Give some examples of lyophilic (hydrophilic) sols

A

Polymers, gums (tragacanth, methylcellulose) and proteins

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6
Q

Give some examples of hydrophobic colloids

A

Particles formed by aggregation of smaller particles (eg protein aggregates) or breakdown of larger particles into colloidal dispersions (emulsions, suspensions)

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7
Q

How do we prepare lyophilic colloidal systems

A

The affinity of the particles to the solvent leads to spontaneous formation of the colloidal dispersion
(This is the easy one)

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8
Q

How do we prepare lyophobic colloidal systems

A

There are 2 methods: dispersion and condensation

Dispersion involves the breakdown of coarse material using a colloidal mill or ultrasonic treatment (this is how we prepare emulsions or graphene suspensions)

Condensation involved the rapid production of supersaturayed solutions causing the formation of colloidal particles (which won’t precipitate). This often occurs during chemical reactions such as colloidal silver iodide. A change of solvent can also produce colloidal particles

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9
Q

Which three techniques can be used to purify disperse systems

A

Dialysis - uses a membrane with pores at an exactly specified size which only allow molecules smaller than the pore size to cross. We use daltons to determine which ones can cross as the molecular weight determines the particle size

Ultrafiltration- uses the same process as dialysis except the solvent is put under pressure to speed the diffusion process up - the solutebwill cross the membrane faster

Electrodialysis - if the molecules are charged, we can apply an electric field to the solution to make the molecules move across the membrane

Bottom line - all follow the same filtering process, the latter two, however are sped up versions

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10
Q

Where do colloids end up after purification

A

They stay on the same side of the membrane - the impurities cross it

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11
Q

Give a summary of the properties of colloidal dispersions (inc. typical size of particles, shapes,light scattering

A

The size range of colloidal particles is wide and are often polydisperse.

The shape varies - they can be spherical, rods, ellipsoid etc

As colloids are large, they scatter light (somethingbwe can use to determine their exact size)

Particles >0.5micrometres will sediment under gravity, smaller ones will require centrifugation

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12
Q

How do we find out the size distribution of a colloidal particle

A

This is given by their pdi- polydispersity index

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13
Q

What are coagulation and flocculation and what causes them

A

They are related to the physical stability of colloidal systems.

Coagulation- permanent contact of particles
Flocculation - temporary contact of particles

They are caused by brownian movement which cause collisions between the dispersed particles. Whether they form floccs or coagules will depend on their forces of attraction and repulsion

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14
Q

What is DLVO and when is it used

A

A theory which explains the aggregation of aqueous dispersions by describing the force between charged surfaces interacting through a liquid medium. It is used mainly with lyophobic colloids and relies on repulsion (elecyrostatic forces, born (short range) and attraction (van der waals)

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15
Q

What happens to hydrophilic compounds in the presence of a hight concentration of electrolytes

A

Theyr lose their salvation water to these ions and will salt out

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16
Q

What is a solvation force and what does it relate to

A

The amount of adsorbed solvent changes on the approach of neighboring particles

They relate to hydrophobic colloids

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17
Q

What is a surfactant and how does it work

A

An amphipathic molecule (they have both lyophilic and lyophobic parts). They are surface active and move at the interface between 2 phases allowing the lyophobic part to evade contact with the solvent

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18
Q

What are micelles and how do they work

A

After covering all the interfaces between the solvent and solute and the surfavtamt concentration continues to increase these surfactants begin to form micelles. These are only present above the critical micelle concentration and, once this has occurred, there is no further reduction in surface tension due to the presence of the surfactant

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19
Q

Name the 4 categories of surfactants (including examples) and explain why they are categorised this way

A

They are categorised by the differences in their hydrophilic heads

Anionic (sodium lauryl sulphate SLS)
Cationic (benzalkonium chloride)
Non-ionic (polysorbates)
Zwitterionic (CHAPS, phosphatidylcholine)

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20
Q

What are they typical characteristics of a micelle

A

Spherical, composed of 50-100 surfactant molecules and 3nm in diameter

21
Q

In which circumstances are non-ionic and cationic surfactants used

A

Non-ionic : parenteral use as they are less toxic

Cationic - external bactericides

22
Q

Which way do micelle surfactants face in aqueous solvent and which way do they face in organic solvent

A

Hydrophilic heads face out to the solvent in aqueous solvent

In organic solvent they are called inverted micelles as the hydrophobic tail faces out to the solvent

23
Q

Why are surfactants used in pharmacy

A

They are used widely in formulation as they can improve wetting, stabilise emulsions and reduce absorption of mass at interfaces. Phenolic compounds such as cresol and thymol are frequently solubilised with surfactants to form a clear solution for disinfection

Non-ionic surfactants (polysorbate etc.) are used to prepare aqueous injections of the water soluble vitamins A,D,E and K

Micellar solutions of penicillin G are 2.5x more stable than the monomers ones

Surcaftants are also used as detergents

24
Q

What is am emulsion and what do they require

A

A mixture of two immiscible liquids, one dispersed in the other. They require emulsifiers to facilitate their formation and stability. They have droplets from 01. to 100micrometers and are inherently unstable (like most disperse systems)

25
Q

Give examples of some emulsifiers

A

Surfactants, polymers, Solid particles, phospolipids, wool fat, beeswax

26
Q

In an oil in water emulsion which is the dispersed phase and which is the continuous phase

A

The oil is the dispersed phase and the water is the continuous phase

27
Q

What is an inverted emulsion

A

An emulsion where the dispersed phase is water and a continuous phase is oil

28
Q

When is an emulsion stable and how is this achieved

A

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

This is achieved by using emulsifiers which form an interfacial film around droplets. For an oil in water emulsion this means that the hydrophobic droplets will be made hydrophilic

29
Q

What causes emotions to crack

A

Any agent that destroys the interfacial film will crack the emulsion. This will happen in the presence of chemicals incompatible with the emulsifier, if there is baterial growth or change of temperature

30
Q

When are emulsions used in pharmacy

A

To formulate creams, ointments and pastes

To administer oils/fat for iv nutrition

Particle size must be controlled to prevent embolism.

31
Q

How do we increase emulsion stability

A

By reducing the droplet size - reduced probability of coalescence

Decreasing the density differences - limiting creaming

increasing the viscosity of the continuous space - slows the movement of particles hence reducing the probability of collision

32
Q

How do we assess stability

A

Visualisation

Monitoring particle size over time using light scattering

33
Q

Define coalescence, flocculation, creaming and phase inversion.

A

Coalescence - Small droplets combine to form larger ones -any electric charge on the particles should result in repulsion

Flocculation - droplets form clusters - this is the combined result of attractive and repulsive forces due to formation of the secondary minimum according to the DVLO theory

Creaming - The dispersed phase rises to the top in an oil in water emulsion or sinks to the bottom in a water in oil emulsion. This is the result of density differences between the phases. It can be redistributed but may result in in appropriate dosage.

Phase inversion - Emotions stabilise of non our emulsifying agents may undergo a phase inversion on heating

34
Q

The choice of oil, emulsifyer and emulsion type used for emulsions depends on route of administration, clinical usability and toxicity

Which oil do we use for:
External applications
Oral emulsions
Parenteral emulsions
Emulsifiers
A

Liquid paraffin, soft or hard paraffin, turpentine oil or silicone oils

Castor oil or liquid paraffin

Limited choice - purified mineral oil for im injections, vegetable oil with long triglycerides

PS80, sorbitol, Pluronic 68, lectins (parenteral) cerimide, sls (topical)
Methylcellulose, aluminium hydroxide (oral)

35
Q

How do we work out the hydrophilic lipophilic balance of an emulsifier

A

A combination of emulsifiers is often used. As the HLB of the emulsifiers need to equate that of the oil phase, you need to work out the HLB of both oil phases then the percentage of the difference of surfactants

36
Q

What type of emulsions are creams (usually)

A

Oil in water. To form the cream, sparingly soluble fatty amphiphiles are combined with more water soluble ionic surfactants. They are stabilised long term by the formation of a viscoelastic gel network phases trapping oil droplets and preventing their movement and interaction

37
Q

What is the gel network theory of emulsion stability

A

A coherent explanation if how fatty ampipjiles and surfactants combined as emulsifiers not only stabilise these creams but also control their consistencies

38
Q

How does swelling impact creams

A

Combinations of fatty alcohols and ionic surfactants exhibit phenomenal swelling.

Importantly, the swelling is electrostatic in nature as the surfactant interpose among the fatty alcohol molecules and electrostatic repulsion between the adjacent bilayers arises from the overlap of the electrical double layers.

Similarly to what was discussed for other dispersed systems, adding electrolytes eg. NaCl to creams reduces the electrostatic swelling between the bilayers, less repulsion, thus the gel network phase volume.

39
Q

Are aerosols more or less stable than colloids

A

Less as they have a liquid continuous phase.

40
Q

What are aerosols and how can they be achieved

A

Collodial dispersions of liquids or solids in gas.

They are achieved using pressurised containers containing liquefied gases as propellant

41
Q

What is a foam

A

A coarse dispersion of the gas in a liquid which is present as thin films or lamellae of colloidal dimensions when the gas bubbles

42
Q

Pure liquids don’t foam, how do we create them then?

A

Transient or unstable forms are obtained with short chain acids and alcohols which mildly surface active. Persistent forms are formed with surfactants

43
Q

Why are foams thermodynamically unstable

A

Due to their vast interfacial area. The gas diffuses from small bubbles to larger ones (reduces surface area) Stability depends on their ability to drain and become thinner and the tendency to rupture in presence of stress (shaking, heat)

44
Q

How are gels formed

A

By the aggregation of colloidal sol particles. The solid/semi solid system is ingerpenetrated by a liquid. Only a small percentage of the disperse phase is needed

45
Q

What is a xerogel

A

The structure left behind when the liquid phase is removed from a gel

46
Q

What is a lyophilic gel

A

One prepared with polymers (agarose)
Type 1 - gel is held together by covalent bonds between the macromolecules. They swell in water and are used for controlled release antibiotics. Example, poly(HEMA) crosslinked with EGDMA
Type 2 - held together with hydrogen bonds and are reversible dependent on temperature

47
Q

What are lyophobic gels

A

A continuous flocclue.

Clays form gels by flocculation in a card house floc network. These gels are also called thixotropic gels as application of force will individualise the particles and break the structure

The forces holding these particles together are weak which gives rise to a secondary minimum.

48
Q

Where are gels particularly used

A

Opthalmic preparations as they undergo gelation at body temperature and have bioadhesive properties

The Medicine 20100 (20 decks)

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