Liquid dosage forms for oral administration Suspensions and Emulsions

Question 1

dispersions in which the drug is dispersed in the external phase (vehicle)

Answer 1

solubility of drug in vehicle is low
Diameter of disperse phase: 0.5 to 100m.
when particle size < 0.5 m: colloidal.

Question 2

unstable suspensions lead to

Answer 2

sedimentation
particle-particle interactions and, ultimately,
caking (compaction).

Question 3

Physical stability of suspensions

Answer 3

1. Electrical properties of dispersed particles
2. distance of separation and the interaction between particles

Question 4

Electrical properties of dispersed particle

Following dispersion within an aqueous medium, particles may acquire a charge due to either

Answer 4

ionisation of functional groups on the drug molecule and/or
adsorption of ions to the surface of the particle.
Following adsorption of ions on to the surface, a phenomenon referred to as the electrical double layer is established

Question 5

The boundary of this second layer will possess a potential, referred to

Answer 5

as the zeta (ζ) potential.

Question 6

Zeta potential measures

Answer 6

measures degree of electric charge on particles relative to bulk medium in which they are suspended

Question 7

to stabilise pharmaceutical suspensions.

Answer 7

compression of the electrical double layer by increased concentration of electrolyte

Question 8

distance of separation and the interaction between particles- has three states of interaction

Answer 8

1. No interaction: particles sufficiently distant from one another. thermodynamically stable state (in absence of sedimentation).
2. Coagulation (agglomeration): particles form an intimate contact with each other; pharmaceutically unacceptable formulation- inability to redisperse the particles upon shaking.
3. Loose aggregation (termed floccules): loose reversible interaction between the particles; enabling the particles to be redispersed upon shaking.

Question 9

DLVO Theory

Answer 9

when dispersed in a liquid medium, particles will experience (electrical) repulsive forces and attractive (London/van der Waals) forces.

energies of attraction ( V a ) and repulsion ( V r )
V t= V a + V r
Where: Overall energy of interaction between the particles ( V t )

Question 10

caking

Answer 10

particles at the bottom of the container are gradually compressed by the weight of those above and, in so doing, sufficient energy is available to overcome the primary maximum (repulsive forces) and the particles become sufficiently close to form an irreversible interaction at the primary minimum.

Question 11

Sedimentation

Answer 11

particles in a suspension will sediment under the influence of gravity and settle at the bottom of the container
larger particles reaching the bottom initially and the smaller particles occupying the space between the larger particles.

Question 12

Stokes’ equation

Answer 12

sedimentation
controlling particle sedimentation may enhance physical stability of pharmaceutical suspensions.
rate of sedimentation may be practically decreased by reducing average particle diameter and increasing viscosity of vehicle.

Question 13

Controlled flocculation

Answer 13

For particles in which the zeta potential (and hence the primary maximum) is high, manipulation of the magnitude of the secondary minimum is required (controlled flocculation).

Flocculation controlled by addition of electrolyte or charged surfactants that reduce zeta potential (and hence VR) to give satisfactory 2ndary minimum in which flocs can be formed.

Question 14

Acceptable suspension

Answer 14

low rate of sedimentation
disperse phase: easily redispersed with gentle shaking
flow properties: formulation easily removed from the container
aesthetically pleasing.

Question 15

Advantages of pharmaceutical oral suspensions

Answer 15

delivery system for low solubility drugs
avoid large volume of solvent- solution of this drug
avoid precipitation upon storage; when co-solvent is used
taste masking of drugs
difficulty in swallowing solid-dosage forms
controlled drug delivery

Question 16

Disadvantages of pharmaceutical oral suspensions

Answer 16

Problems: correct dose of drug?
unstable; formulation to ensure stability over the period of the shelf-life
aesthetic suspension: difficult
bulky, difficult for patient to carry.

Question 17

Formulation considerations: Physical properties

Answer 17

Particle size:  stability by modifying rate of particle sedimentation (Stokes law)
Particle size should be minimised
chemical methods (controlled precipitation)
physical methods (i.e. milling).
B. Wetting properties of drug
Insoluble drug particles: hydrophobic, not easily wetted
surface-active agents: interfacial tension
particles poorly wetted: aggregation