Oral Suspensions Flashcards
What is a disperse system?
Two-phase heterogenous system in which an insoluble or immiscible dispersed phase is distributed through continuous phase
What are dispersed systems classified upon?
Size of dispersed phase
What is a colloidal system?
Particle size less than 1 micro meter
What is a coarse system?
Particle size more than 1 micro meter
What is a pharmaceutical suspension?
Liquid disperse system consisting of particles distributed within liquid vehicle
What is the particle size of pharmaceutical suspension?
0.1-10 micro meter
What is the ideal suspension?
Solid materials monodispersed as spheres + evenly suspended
THIS IS A CHALLENGE THO
To ensure uniform dose, a suspension must have what properties?
Particles settle slowly
Particles readily + uniformly re-dispersed upon shaking
Particle size remains constant over time
Viscosity high enough to ensure uniform dose
Why can’t the viscosity be too high?
As it wouldn’t be easy to pour
What is the solvent for particle-liquid interaction?
H2O
How do hydrophobic drug particles acquire charge?
Due to ionisation of H2O
What happens if a drug can be ionised?
Show reasonable degree of aq solubility
What happens in aq solution?
H2O undergo self-ionisation + produce ions
H2O ⇌ H+ + OH-
What happens in electrical double layer interaction?
Drug particle surface give apparent negative charge in liquid
System needs to maintain overall neutral charge
Cations form layer round “anionic” solid particle = electrical double layer
Can excipients affect suspension properties?
YES
What do ionic salts do?
Increase no. of mobile charges
At a low conc of ionic salt what happens?
Affect diffuse layer
= easier to neutralise particle charge, thinning diffuse layer
At high conc of ionic slat what happens?
Affect fixed layer
= charge of particle surface decrease
What is the critical micelle conc (CMC)?
Conc of surfactants above micelle form
What happens when above CMC?
Micelles form hydrophobic core in which hydrophobic drug may dissolve
What happens when below CMC?
Surfactants will cover particles surface
= reduce interfacial tension between particle + liquid medium
What is the DVLO theory?
Explains aggregation of aq dispersions + forces between charged surfaces interacting within liquid
What does DVLO theory calculate?
Attraction + repulsion energies between particles, together with energy of interactions
What is the DVLO used to do?
Predict behaviour of suspension
Will particle coalesce + settle?
OR
Will particle remain homogenously dispersed in suspension?
What do particles dispersed in a liquid exhibit?
Van der Waals + electrical repulsion forces
What do forces at surface of particle determine?
Degree of flocculation + aggregation
What is the deflocculated system?
A system in which particles are individually + uniformly dispersed throughout liquid medium
When will system remain deflocculated?
When repulsive energy between suspended particle are high
What happens if deflocculated particles settle?
Form a layer of particle sediment at bottom of suspension = difficult to re-suspend
What is a flocculated system?
A system in which suspended particles are formed into floccules rather than separate particles
When does a flocculated system occur?
When attractive forces between particles slightly greater than repulsive forces
What does controlled flocculation prevent?
Particles caking in suspension formulations
What is one way of inducing flocculation?
Reducing surface of charge of particle
= adding surfactants + ionic salts
What is particle movement caused by?
Brownian motion
Gravity
External agitation - eg. shaking
What does particle motion affect?
Inter-particulate distance = affecting flocculation status of suspension
Which particles are subject to Brownian motion?
Small particles
Less than 2 micro meters
What does diffusion provide?
More homogenous movement within medium
Why is diffusion less likely to be seen in flocculated system?
Larger particles to be above affective diffusion size
What happens to diffusion if you increase viscosity?
Decreases
What is sedimentation?
Downward particle movement due to gravity
When does sedimentation occur?
Particles less than 0.5 micro meters
What happens to sedimentation if you increase viscosity?
Decreases
How do you control sedimentation?
Reduce rate
What is 1st way of controlling sedimentation?
Decrease particle size = increase diffusion
What is 2nd way of controlling sedimentation?
Decrease particle density
What is 3rd way of controlling sedimentation?
Increase medium density
eg. add dextrose
What is 4th way of controlling sedimentation?
Increase medium viscosity
eg. add polymers
What is 5th way of controlling sedimentation?
Increase temp = increase diffusion constant
Which excipients improve palatability?
Flavours, sweeteners + colouring Preservatives Buffers Suspending agents Chemical stabilisers Wetting agents Flocculating agents
What are common sweeteners?
Saccharin sodium
Acesulfame potassium
What do you have to consider with sweeteners?
Effect on double electrical layer
Why are preservatives used?
Prevent microbe growth
What are examples of preservatives?
Sorbic acid + benzoic acid
Parabens
What do you have to consider with preservatives?
Effect on flocculation
Why are buffers used?
Maintain pH of aq system
What do you have to consider with buffers?
Effect flocculation behaviour
Why are suspending agents used?
Reduce particle sedimentation
What is 1st choice for suspending agents?
H2O soluble cellulose polymers
eg. hydroxypropyl methylcellulose (HPMC)
eg. sodium salt of carboxymethylcellulose (NaCMC)
What is 2nd choice for suspending agents?
Sodium alginate
What are problems with sodium alginate?
Easily ionised = affect flocculation
Why are chemical stabilisers used?
Improve chemical stability of drug
What are examples of chemical stabilisers?
Antioxidants
Chelators
Why are wetting agents used?
Reduce interfacial tension between particle + liquid medium
What do wetting agents improve?
Homogeneity of drug particle distribution
Why are flocculating agents used?
Adjust flocculation status of particles
What is an example of flocculating agent?
Ionic material - eg. NaCl
Why are sweeteners used?
Improve patient acceptability + palatability
