Suspensions As Dosage Forms Flashcards
List 4 ways that suspensions can be administered
Oral
Topical
Pareneteral
Inhalations
Describe oral administration of solutions
Materials need to be in finely divided form in gastrointestinal tract
More palatable than solutions in children
What is benefit of administering suspensions via the parenteral route?
Can control the rate of absorption of the drug
What is the benefit of having suspensions inhaled?
Prolonged release of volatiles
What kind of drugs are formulated as suspensions?
Poorly soluble drugs
List 3 advantages of using pharmaceutical suspensions
- Useful for formulation of low solubility drugs
- Effective at masking taste
- Ideal for patients who have difficulty swallowing solid dosage forms
List 3 disadvantages of using pharmaceutical suspensions
- Fundamentally unstable
- Aesthetic suspension formulation difficult to attain
- Bulky formulations
List 3 desired features of a pharmaceutical suspension
- Dispersion should settle slowly and be easily dispersed with gentle shaking
- Particle size of dispersed medium should remain constant
- Suspension should pour readily and evenly
List 2 parameters of the dispersed phase we can control
- Particle size
2. Surface properties of particles
List 2 parameters of the vehicle/continuous phase we can control
- Viscosity
- Use of electrolytes
- Addition of surfactants
What affect does particle size have on the suspension?
- Small fine powder for slow sedimentation
- Particles >5um = gritty texture
- Particle size controls rate of dissolution
How can crystal growth in the suspension occur?
- Smaller particles dissolve and larger particles grow
- Happens on storage where temperature variation can alter solubility of a slightly soluble drug
How can crystal growth be prevented?
Polymeric colloids or surfactants
List 2 ways that the sedimentation rate can be reduced
- Reducing size of particle (h/e fine particles can form cakes)
- Increasing viscosity of medium
How does the shape of the particles affect sedimentation of the suspension?
Barrel shaped = more stable dispersions
Needle shaped = cake
What is DVLO theory?
An explanation of the stability of a colloidal suspension
It describes the balance between electrostatic repulsion and Van der Waals attraction = total interaction energy
Therefore - system will be stable if repulsive forces prevent interaction between particles
What does the primary minimum represent?
Coagulation
What does the first peak in an energy of interaction vs particle separation graph represent?
The energy barrier to coagulation
What does the secondary minimum represent?
Flocculation
What are the attractive interactions involved in DVLO theory?
Van der Waals interactions
= a volume force
What are the repulsive interactions involved in DVLO theory?
Forces between bound surface ions = a surface force
Electrostatic & steric hindrance between polymer chains
What is the electrical double layer?
A structure which appears on the surface of a solid when it is exposed to a fluid
2 parallel layers of charge surrounding the solid
1st layer = the surface charge = ions adsorbed onto the object due to chemical interactions
2nd layer = diffuse layer = ions attracted via the surface charge
What affects the thickness of the double layer?
Electrolyte concentration (increase = decrease in thickness) Surface potential (charge on particle)
What does the approach of particles coated with hydrated polymer lead to?
Leads to repulsion of particles
Due to steric hindrance (positive enthalpy change & negative entropy change) and osmotic pressure
List 5 problems that need to be overcome into order to create a stable suspension formulation
- Sedimentation
- Caking
- Flocculation
- Particle growth (crystals?)
- Adhesion to container wall
What is the main role of excipients in suspensions?
To stabilise the suspension of particles
Control sedimentation and limit aggregation or crystal growth
What is the affect of adding wetting agents to a suspension?
Reduces surface tension
Reduce interfacial tension between particle and dispersed medium
Define: Wettability
The tendency of 1 liquid to adhere to a solid surface in the presence of other immiscible fluids
What does deflocculation lead to?
A cake or clay formation
Slow sedimentation so prevents medium becoming trapped (like in flocculation) = compacted
Very difficult to redisperse
What is flocculation?
Secondary minima
Loose aggregation
Particles sediment rapidly entrapping continuous phase and remaining discrete
This means it is easily dispersed
What happens if the electrolyte concentration is increased too much?
The repulsive interactions weaker and eventually barrier to coagulation is removed = coagulated and stable aggregate - bad
What is a potential problem of wetting agents?
Can often lead to a deflocculated suspension due to reduction in interfacial tension
What is controlled flocculation?
Prepare partially flocculated system:
- Control particle size
- Control zeta potential (by adding electrolytes)
- Addition of polymers (to promote crosslinking)
What is the role of flocculating agents?
Support the ‘floc’ and increase sedimentation volume
List 3 things that could be used as flocculating agents
- Electrolytes - ions of opposite charge will reduce thickness of double layer = secondary minimum (flocculation)
- Surfactants = affect electric (zeta) potential
- Hydrophilic polymers = adsorb to particles leading to loosely flocculated structures
What affect does the addition of electrolyte have?
Electrolyte reduces thickness of double layer = flocculated system
H/e add to much = coagulation
How can a system go from deflocculated to partially flocculation?
Add flocculating agent:
Electrolytes, surfactants or hydrophilic polymers
Define: Newtonian flow
Constant viscosity regardless of shear rate
Deflocculated system
Define: Non-Newtonian flow
Change in viscosity with increasing shear rate
Flocculated system
Define: Shear rate
Gradient of velocity in a flowing material
How is sedimentation quantified?
Ratio of sedimentation layer volume:total suspension volume
What is the degree of flocculation measured by?
Determined by sedimentation volume
Why are electrolytes common excipients in suspensions?
Electrolytes control flocculation
Why are surfactants common excipients in suspensions?
Act as wetting agents and flocculauting agents
Why are hydrophilic polymers common excipients in suspensions?
Enhance physical stability - wetting/flocculating agents
Enhance rheological stability - viscosity agents
How does the viscosity of a suspension affect its absorption in the GIT?
High viscosity = slow dissolution
How does the suspension’s slower dissolution rate than solution make it preferable in some circumstances?
Slower dissolution rate = can control rate of release in injection
List 5 criteria of suspending agents
- Be readily and uniformly incorporated into formulation
- Be readily dispersed in water without special techniques
- Ensure no caking
- Must not influence dissolution rate or absorption rate
- Be non-toxic
