Routes of Administration Oral (Suspensions)

Question 1

What is a disperse system?

Answer 1

• A 2 phase heterogenous system in which an insoluble or immiscible dispersed phase is distributed through a continuous phase
• Are classified upon the size of dispersed phase

Question 2

What are the different dispersion classifications?

Answer 2

• Molecular (less than 1nm) (Glucose solution)
• Colloidal (between 1nm and 1um) (microemulsions, micelles, milk)
• Coarse (more than 1um) (suspensions, emulsions)

Question 3

What are suspensions?

Answer 3

• Liquid disperse system consisting of particles distributed within a liquid vehicle
• Classified as coarse or colloidal depending on size
• Not optically clear = cloudy

Question 4

What are the reasons of suspensions?

Answer 4

• Deliver poorly water-soluble drugs which cant be formulated as aqueous solutions
• Mask bitter taste
• Increase drug stability
• Achieve controlled/ sustained drug release

Question 5

To ensure a uniform dose, what properties should an oral suspension have?

Answer 5

• Particles settle slowly
• Particles readily and uniformly re-dispersed upon shaking
• Particle size remains consistent over time
• Viscosity is high enough to ensure a uniform dose (not too much or unpourable)

Question 6

What is the Electrical double layer?
Explanation from centre to outside

Answer 6

• Negatively charged particle
• Stern Layer: Particle attracts ions of opposite charge (positive), tightly bound around surface
• Hydrodynamic plane of shear (slipping plane)
• Diffuse Layer - ions are diffused freely around particle

Question 7

What is zeta potential?

Answer 7

• Governs the degree of repulsion/ attraction between particles
• The electrical potential in the interfacial double layer at the slipping plane

Question 8

What happens if the zeta potential is reduced below a certain value?

Answer 8

• The attractive forces between particles due to van der waals overcome the forces of repulsion and the particles come together to form floccules - flocculation
• The magnitude of surface and zeta potentials is related to the surface charge and the thickness of the double layer

Question 9

What happens if the zeta potential is high?

Answer 9

• The stronger the electrostatic repulsion and the more stable the system (low viscosity, well dispersed)

Question 10

Excipients (ionic charge NaCl) how do they affect the suspension properties?

Answer 10

• At low conc - will only affect the diffuse layer, neutralising the particle charge, thinning diffuse layer
• At high conc - will also affect fixed layer charge. Charge on particle surface will decrease

Question 11

How do micelles affect the electrical double layer? what happens if the concentration is above or below the CMC

Answer 11

• Critical micelle concentration is the concentration in which micelles form
• Above CMC, micelles form with a hydrophobic core in which hydrophobic drug may dissolve
• Below CMC, surfactants will cover particle surface and reduce interfacial tension between particle and medium (increase stability)

Question 12

What is the DVLO theory?

Answer 12

• It explains the aggregation (cluster) of aqueous dispersions and the forces between charges surfaces interacting with the liquid.
• It calculates the attraction (van der waals) and repulsion energies (electrostatic potential) between particles with energy of the interactions.

Question 13

What is a deflocculated system?

Answer 13

• A system in which particles are individually and uniformly dispersed throughout the liquid medium
• Remains deflocculated when repulsive energies are high and may settle slowly producing sediment (not ideal)
• Redispersion is hard

Question 14

What is a Flocculated System?

Answer 14

• Forms weakly attracted or weakly bonded aggregates of particles
• When attractive forces are greater than repulsive
• Reducing surface charge of particles can induce flocculation

Question 15

What are the different ways particles move?

Answer 15

• Brownian Motion
• Gravity
• External agitation (shaking by patients)

Question 16

What is sedimentation?

Answer 16

• Downward movement of particles due to gravity
• Occurs with molecules bigger than 0.5um
• Reducing particle size and increasing viscosity reduces sedimentation rate

Question 17

How do you reduce sedimentation?

Answer 17

• Particle size reduction
• Reduce particle density
• Increase medium density
• Increase medium viscosity
• Increase temperature (increases diffusion constant)

Question 18

Why use excipients like flavourings and colourings?

Answer 18

• Improve patient acceptability and palatability
• Suspensions are less tense in taste than solutions
• Traditionally sucrose used however problems with diabetes

Question 19

Why use preservatives and name examples?

Answer 19

• Prevent microbial growth
• Sorbic acid and benzoic acid (affects flocculation - partially ionises)
• Parabens

Question 20

Why use buffers?

Answer 20

• To maintain pH of aqueous mixture
• Ionic in nature so will affect flocculation

Question 21

Why use suspending agents?

Answer 21

• Reduce particle sedimentation
• 1st choice = water soluble cellulose polymers or sodium alginate

Question 22

What are flocculating agents?

Answer 22

• Decrease zeta potential of suspended charged particle - causes aggregation
• Examples: Surfactants, ionic materials

Question 23

What do chemical stabilisers do and name examples?

Answer 23

• Improve chemical stability
• Antioxidants and Chelators

Question 24

What are wetting agents and name examples?

Answer 24

• Reduce interfacial tension between the particle and liquid medium
• Improve homogeneity of drug distribution
• E.g using micelles below CMC