Disperse systems 2

Question 1

Definition and characteristics of suspensions

Answer 1

Formulations of small, insoluble solid particles distributed throughout a liquid continuous phase
Faster absorption than from solid dosage form
Slower absorption than from a solution

Question 2

Wetting

Answer 2

The ability of a solid to stay in contact with a liquid
Must be the first stage of making a suspension otherwise particles remain on the surface, attach to the container or form large clumps within the liquid
Wetting agents decrease interfacial tension to allow wetting and help dispersion

Question 3

Wetting of diffusible solids, indiffusible solids and finely divided substances

Answer 3

Diffusible solids: easily wetted so straightforward to suspend
Indiffusible: show some hydrophobicity so are not easily wetted, and need a wetting agent
Finely divided substances are particularly difficult to wet due to the presence of an adsorbed layer of air around the particles

Question 4

Interfacial tension

Answer 4

The molecules of a compound prefer to be in contact with other like molecules than with different molecules
The degree of wetting is determined by the difference between the adhesive and cohesive forces

Question 5

Cohesive and adhesive forces

Answer 5

Cohesive forces exist between the molecules in each phase
Adhesive forces exist between the two phases
The cohesive forces are greater than the adhesive forces, and this leads to an imbalance of forces (tension) at the interface

Question 6

Types of wetting agent

Answer 6

Surface Active Agents (detergents)- hydrocarbon chains are adsorbed by hydrophobic particle surfaces while polar groups enter the liquid and become hydrated, may cause excessive foaming or deflocculate
Hydrophilic colloids- coat the solid hydrophobic particles with a layer, giving the particle a hydrophilic character, can be used in combination with SAAs, may deflocculate
Solvents- water miscible solvents decrease interfacial tension by penetrating powder clumps and displacing air

Question 7

Emulsion definition

Answer 7

An emulsion is a mixture of two or more immiscible liquids, one liquid is dispersed as small globules throughout the other

Question 8

Emulsions

Answer 8

Because emulsions are unstable, globules tend to coalesce and adopt a spherical shape
Emulsions can be created by shaking two liquids together, but the resulting emulsion is temporary
Emulsions almost always require an emulsifier/ emulsifying agent

Question 9

Oral uses of emulsions

Answer 9

Convenient way of giving water insoluble drugs
Mask unpleasant tasting drugs
Some oil soluble compounds have increased absorption from GI tract when emulsified than when given as an oily oral solution

Question 10

Parenteral uses of emulsions

Answer 10

Some parenterals work faster as an emulsion than an oil
w/o injections given im can act as depots
o/w systems are used to supply lipids in iv nutrition

Question 11

Uses of multiple emulsions e.g. w/o/w, o/w/o

Answer 11

Carrier systems for protein or peptide drugs e.g. insulin
To encapsulate drugs to protect them from physiological environment
Controlled release drug delivery

Question 12

Determining emulsion type

Answer 12

Miscibility tests: emulsions are miscible with liquids
that are miscible with their continuous phase i.e. o/w are
miscible with water and vice versa.
Staining with dye: dyes will dissolve in and colour the
phase with which they are miscible e.g. with oil-soluble
dye w/o emulsions look darker than o/w and, under a
microscope, coloured globules on a colourless
background are seen.
Conductivity tests: systems with aqueous continuous
phases (o/w) will conduct electricity, but those with oily
continuous phases (w/o) will not.

Question 13

Definitions of emulsion stability

Answer 13

Globules remain uniformly distributed throughout the continuous phase
Globules retain their original character
Phases stay mixed
Emulsion retains its original physical properties

Question 14

Flocculation

Answer 14

Dispersed globules get closer together, but within flocs, globules remain separate, so it is a reversible state
Due to the closeness of flocculated globules, any weakness in the interfacial film may result in irreversible coalescence

Question 15

Creaming

Answer 15

Is a result of flocculation
Dispersed phase rises to the top or settles to the bottom of the emulsion
Can be redispersed because each globule is still surrounded by its protective film of emulsifier
Likelihood of cracking is increased because globules in cream layer are close to each other

Question 16

Cracking

Answer 16

Coalescence or breaking
Complete and irreversible separation of the emulsion into its constituent phases
When the globules of the dispersed phase coalesce, the system reverts to two separate layers
Cannot be redispersed by shaking because the film surrounding the particles has been destroyed
Can be caused by pH or chemical instability

Question 17

Phase inversion

Answer 17

Can be caused by heat, chemical instability or phase volume ratio > 60-70% dispersed phase
Indicates instability if spontaneously occurring
Sometimes used in manufacturing to obtain a finer product

Question 18

Problems of emulsion instability

Answer 18

Pharmaceutically inelegant- negative effects of patient compliance and confidence in product
Lack of homogeneity- potential for drug over/ underdose
Phase separation in parenteral emulsions- free oil can block small blood vessels, leading to decreased bloodflow, and potentially to pulmonary embolism and death
Increased rate of drug release- for multiple emulsions used to control rate, possible leading to overdose

Question 19

Stabilising emulsions

Answer 19

If an emulsifier is added to a mixture of water and oil, polar groups associate with water molecules while non-polar parts enter the oil phase
For an emulsifier to concentrate at an interface there must be a balance between its hydrophilic and lipophilic characteristics

Question 20

Ways of stabilising emulsions

Answer 20

Form an interfacial film to help prevent coalescence when globues come into contact
Reduce interfacial tension
Give surface charge to globules, causing electrostatic repulsion
Prevent globules coming into close contact by steric hindrance of hydrated side chains
Increased continuous phase viscosity slows globule movement and decreases likelihood of meeting

Question 21

Oily suspensions

Answer 21

Most pharmaceutical suspensions consists of
solid drug particles in aqueous vehicles, but oily
or organic liquids are sometimes used
Some antipsychotics and steroids (e.g.
contraceptives) are formulated as oily suspensions
(“depots”) which remain as oily globules after
injection, thus reducing surface area in contact with
physiological fluids and therefore rate of absorption