PH2107 - suspension, colloids & nanoparticles 2 Flashcards
What is Brownian motion?
Random, zig-zag movement of a colloidal particle in a continuous phase
What causes Brownian motion?
Continuous collisions with continuous phase molecules and other particles, shoving it in different directions
What size particles are affected by Brownian motion?
Up to ~ 5um
How can the tracks of Brownian motion be tracked?
Using a microscope
What factors affect particle velocity in Brownian motion?
- decreasing size
- decreasing continuous phase viscosity
- increasing temperature
What is diffusion?
Spontaneous movement of particles or molecules from regions of high concentration to lower concentration
What is Fick’s first law?
Drug flux is proportional to the diffusion co-efficient, D, and the negative gradient of concentration
J = -D δC/δx
What does the negative sign in Fick’s law of diffusion?
The negative sign indicates that J is positive when movement is down the gradient and cancels the negative gradient along the direction of positive flux
How can diffusion be enhanced?
Increase drug concentration gradient - higher drug concentration - increase dose retention or reduce washout Modify the diffusivity of the barrier - microneedles - electroporation - cryoprobe
What keeps small particles moving in a colloidal dispersion?
Brownian motion
What effect does gravity have on particles in a colloidal dispersion?
As the particles get bigger in a colloidal suspension, the influence of gravity is greater
What is the result if the only force acting on small particles is Brownian motion?
Particles won’t sediment
When does gravity become significant?
When particle size is larger than 0.5 - 1um
What effect does gravity have on particles which are larger than 0.5 - 1um?
Causes them to eventually settle to the bottom of the formulation?
Why is sedimentation a problem with pharmaceutical products?
- loss of homogeneity
- danger of variable dosing
- re-suspension difficulties
What is Stoke’s Law?
Describes the velocity of sedimentation for a particle falling through a liquid
ν = 2d^2 g (σp – ρm) / 9η
ν velocity of sedimentation, d particle radius, g acceleration due to gravity, σ particle density, ρ density of medium, η viscosity of medium
What is sedimentation rate decreased by?
- reducing particle size
- increasing density of liquid continuous phase
- increasing viscosity of liquid continuous phase
What is flocculation?
The process where fine particles are caused to clump together into a floc
- particle size increases from submicroscopic microfloc to visible macroflocs
What is creaming?
Process where a floc floats to the top of the liquid
What is sedimentation?
Process where a floc settles to the bottom of the liquid
How can flocs be removed from a liquid?
By filtration
What is coagulation?
Addition of a coagulant (oppositely charged chemicals) during relatively intense mixing to destabilise naturally occurring particles and macromolecules and/or to precipitate additional particles
What is wetting?
The affinity between particles and molecules of continuous phase
Give three examples of wetting agents
- ethanol
- glycerol
- glycols
What is viscosity?
The resistance of a fluid to flow/movement due to internal friction
What is the relationship between viscosity and the force required to make it move at a given rate?
The more viscous the liquid, the greater the force required to make it move at a given rate
What does viscosity in a disperse system depend on?
- particle molecule
- particle shape
- spherocolloid - low viscosity
- linear particles - more viscous dispersion
- particle chemistry
- particle concentration
- continuous phase nature
- temperature
How is rheology relevant in manufacturing pharmaceutical products?
- mixing
- passing through machinery
- pouring / packing bottles
How is rheology relevant in patient issues with pharmaceutical products?
- physical stability
- ease of use (e.g. pouring, spreading, injecting)
- safety (consistent dosing)
What is rheology ?
The study of flow
How is rheology relevant during storage (low shear) of pharmaceutical products?
A high viscosity is required to prevent/decrease sedimentation. In addition to this, a low viscosity on shaking (high shear) is preferred
In the manufacturing process, what property do materials need so they can be processed, then dispensed into a container, remain stable over time, dispensed, handled and properly applied to the affected area by patients?
Specific flow properties
What parameter is crucially important as it will directly affect the way a drug is formulated and developed, the quality of the raw and finished product, the drug efficacy, the way a patient adheres to the prescribed drug and the overall healthcare cost
Rheology
What effect does a flocculated suspension have on viscosity?
The viscosity of a flocculated suspension is greater than when de-flocculated
What characteristic will a flocculated suspension have?
It will have a ‘yield value’ like a plastic (sometimes pseudo-plastic system)
What is Einstein’s law?
An equation to calculate the viscosity of a dispersion
The viscosity of a dispersion η can be calculated:
η = ηo (1 + 2.5 Φ)
ηo is viscosity of continuous phase,
Φ is volume/parts of dispersed phase
What is the difference in viscosity between a flocculated and deflocculated suspension ?
Flocculated has greater viscosity
A flocculated suspension will have a ‘yield value’ like a plastic (pseudo-plastic) system
polydisperse formulations have lower viscosity
monodisperse formulations have higher viscosity
What assumptions are made in Einstein’s law?
- it is a dilute suspension (up to ~5% particle concentrations)
- the particles are rigid and spherical
- there are no interparticulate interactions
- the liquid behaves in a simple, predictable way
- Brownian motion effects are unimportant
What is the relationship between temperature and viscosity of a substance?
Generally, as the temperature of a formulation increases, its viscosity decreases
What does thermal input cause in a formulation?
Thermal input causes a reduction in the cohesive forces while simultaneously increasing the rate of molecular interchange (Brownian motion )
What are the exceptions to the general rule of an increase in temperature causes a decrease in viscosity?
Pluronics - poloxamers are nonionic triblock copolymers
- liquid at lower temperatures
- gel at higher temperatures
- ‘sol-gel’ transition at 37C useful e.g. implants
What is the relationship between dispersity and viscosity?
Wider particle size distribution = lower viscosity
- polydisperse formulations have lower viscosity
- monodisperse formulations have higher viscosity
What is shearing stress?
The force per unit area required to cause a liquid to flow
What is the “rate of shear”?
The difference in velocity between two planes of liquid a given distance apart
Who noticed that in most liquids the rate of flow was directly related to the force applied, by the constant viscosity (resistance to flow)?
Newton
What is the relationship between the viscosity of a liquid and the force per unit area required to produce a given flow rate?
The greater the viscosity of a liquid, the greater the force per unit area required to produce a given flow rate
How does a Newtonian fluid behave?
They continue to flow in the same way, regardless of the forces acting on them
What is the relationship between rate of flow (shear) and the applied force (stress)?
Rate of flow is directly proportional to applied force
dynamic viscosity, η:
η = σ / γ
(shear, γ)
(stress, σ).
What can cause the viscosity of a solvent (water) to change?
The viscosity of a solvent (water) doesn’t change with shear rate, but it can can change depending on the contents it holds
What causes a material to change from Newtonian to non-Newtonian behaviour?
Changing from a single to a multiphase system
What factors could change a material from a Newtonian fluid to a non-Newtonian fluid?
- properties related to the solid particles in the dispersed phase (e.g. size, shape, aspect ratio, porosity, aggregation)
- the properties of rheology modifiers (e.g. one or multipolymer system, short or long chain polymer, crosslinked chains)
- nature of the suspension itself (whether it’s diluted or concentrated)
What is plastic behaviour?
Characterised by a minimum force beyond which the material flows (yield stress)
When is plastic behaviour observed?
In concentrated suspensions with flocculated particles and high viscosity continuous phases
What is pseudoplastic flow?
When viscosity decreases with the rate of shear but no yield stress
What is pseudoplastic flow also known as?
Shear thinning
What causes a material to display pseudoplastic flow?
Flocculated dispersions containing long, high molecule weight molecules
When does dilatant flow occur?
When viscosity increases with the rate of shear
What is dilatant flow also known as?
Shear thickening
The opposite of pseudo plastic flow
What causes dilatant flow?
Dispersions containing a high concentration of small, deflocculated particles
