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MPharm 2 - PH2107 > PH2107 - suspension, colloids & nanoparticles 2 > Flashcards

PH2107 - suspension, colloids & nanoparticles 2 Flashcards

1
Q

What is Brownian motion?

A

Random, zig-zag movement of a colloidal particle in a continuous phase

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2
Q

What causes Brownian motion?

A

Continuous collisions with continuous phase molecules and other particles, shoving it in different directions

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3
Q

What size particles are affected by Brownian motion?

A

Up to ~ 5um

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4
Q

How can the tracks of Brownian motion be tracked?

A

Using a microscope

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5
Q

What factors affect particle velocity in Brownian motion?

A
  • decreasing size
  • decreasing continuous phase viscosity
  • increasing temperature
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6
Q

What is diffusion?

A

Spontaneous movement of particles or molecules from regions of high concentration to lower concentration

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7
Q

What is Fick’s first law?

A

Drug flux is proportional to the diffusion co-efficient, D, and the negative gradient of concentration

J = -D δC/δx

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8
Q

What does the negative sign in Fick’s law of diffusion?

A

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

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9
Q

How can diffusion be enhanced?

A 
Increase drug concentration gradient
- higher drug concentration
- increase dose retention or reduce washout
Modify the diffusivity of the barrier
- microneedles
- electroporation
- cryoprobe
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10
Q

What keeps small particles moving in a colloidal dispersion?

A

Brownian motion

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11
Q

What effect does gravity have on particles in a colloidal dispersion?

A

As the particles get bigger in a colloidal suspension, the influence of gravity is greater

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12
Q

What is the result if the only force acting on small particles is Brownian motion?

A

Particles won’t sediment

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13
Q

When does gravity become significant?

A

When particle size is larger than 0.5 - 1um

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14
Q

What effect does gravity have on particles which are larger than 0.5 - 1um?

A

Causes them to eventually settle to the bottom of the formulation?

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15
Q

Why is sedimentation a problem with pharmaceutical products?

A
  • loss of homogeneity
  • danger of variable dosing
  • re-suspension difficulties
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16
Q

What is Stoke’s Law?

A

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

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17
Q

What is sedimentation rate decreased by?

A
  • reducing particle size
  • increasing density of liquid continuous phase
  • increasing viscosity of liquid continuous phase
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18
Q

What is flocculation?

A

The process where fine particles are caused to clump together into a floc
- particle size increases from submicroscopic microfloc to visible macroflocs

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19
Q

What is creaming?

A

Process where a floc floats to the top of the liquid

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20
Q

What is sedimentation?

A

Process where a floc settles to the bottom of the liquid

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21
Q

How can flocs be removed from a liquid?

A

By filtration

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22
Q

What is coagulation?

A

Addition of a coagulant (oppositely charged chemicals) during relatively intense mixing to destabilise naturally occurring particles and macromolecules and/or to precipitate additional particles

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23
Q

What is wetting?

A

The affinity between particles and molecules of continuous phase

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24
Q

Give three examples of wetting agents

A
  • ethanol
  • glycerol
  • glycols
25
Q

What is viscosity?

A

The resistance of a fluid to flow/movement due to internal friction

26
Q

What is the relationship between viscosity and the force required to make it move at a given rate?

A

The more viscous the liquid, the greater the force required to make it move at a given rate

27
Q

What does viscosity in a disperse system depend on?

A
  • particle molecule
  • particle shape
  • spherocolloid - low viscosity
  • linear particles - more viscous dispersion
  • particle chemistry
  • particle concentration
  • continuous phase nature
  • temperature
28
Q

How is rheology relevant in manufacturing pharmaceutical products?

A
  • mixing
  • passing through machinery
  • pouring / packing bottles
29
Q

How is rheology relevant in patient issues with pharmaceutical products?

A
  • physical stability
  • ease of use (e.g. pouring, spreading, injecting)
  • safety (consistent dosing)
30
Q

What is rheology ?

A

The study of flow

31
Q

How is rheology relevant during storage (low shear) of pharmaceutical products?

A

A high viscosity is required to prevent/decrease sedimentation. In addition to this, a low viscosity on shaking (high shear) is preferred

32
Q

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?

A

Specific flow properties

33
Q

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

A

Rheology

34
Q

What effect does a flocculated suspension have on viscosity?

A

The viscosity of a flocculated suspension is greater than when de-flocculated

35
Q

What characteristic will a flocculated suspension have?

A

It will have a ‘yield value’ like a plastic (sometimes pseudo-plastic system)

36
Q

What is Einstein’s law?

A

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

37
Q

What is the difference in viscosity between a flocculated and deflocculated suspension ?

A

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

38
Q

What assumptions are made in Einstein’s law?

A
  • 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
39
Q

What is the relationship between temperature and viscosity of a substance?

A

Generally, as the temperature of a formulation increases, its viscosity decreases

40
Q

What does thermal input cause in a formulation?

A

Thermal input causes a reduction in the cohesive forces while simultaneously increasing the rate of molecular interchange (Brownian motion )

41
Q

What are the exceptions to the general rule of an increase in temperature causes a decrease in viscosity?

A

Pluronics - poloxamers are nonionic triblock copolymers

  • liquid at lower temperatures
  • gel at higher temperatures
  • ‘sol-gel’ transition at 37C useful e.g. implants
42
Q

What is the relationship between dispersity and viscosity?

A

Wider particle size distribution = lower viscosity

  • polydisperse formulations have lower viscosity
  • monodisperse formulations have higher viscosity
43
Q

What is shearing stress?

A

The force per unit area required to cause a liquid to flow

44
Q

What is the “rate of shear”?

A

The difference in velocity between two planes of liquid a given distance apart

45
Q

Who noticed that in most liquids the rate of flow was directly related to the force applied, by the constant viscosity (resistance to flow)?

A

Newton

46
Q

What is the relationship between the viscosity of a liquid and the force per unit area required to produce a given flow rate?

A

The greater the viscosity of a liquid, the greater the force per unit area required to produce a given flow rate

47
Q

How does a Newtonian fluid behave?

A

They continue to flow in the same way, regardless of the forces acting on them

48
Q

What is the relationship between rate of flow (shear) and the applied force (stress)?

A

Rate of flow is directly proportional to applied force

dynamic viscosity, η:
η = σ / γ

(shear, γ)
(stress, σ).

49
Q

What can cause the viscosity of a solvent (water) to change?

A

The viscosity of a solvent (water) doesn’t change with shear rate, but it can can change depending on the contents it holds

50
Q

What causes a material to change from Newtonian to non-Newtonian behaviour?

A

Changing from a single to a multiphase system

51
Q

What factors could change a material from a Newtonian fluid to a non-Newtonian fluid?

A
  • 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)
52
Q

What is plastic behaviour?

A

Characterised by a minimum force beyond which the material flows (yield stress)

53
Q

When is plastic behaviour observed?

A

In concentrated suspensions with flocculated particles and high viscosity continuous phases

54
Q

What is pseudoplastic flow?

A

When viscosity decreases with the rate of shear but no yield stress

55
Q

What is pseudoplastic flow also known as?

A

Shear thinning

56
Q

What causes a material to display pseudoplastic flow?

A

Flocculated dispersions containing long, high molecule weight molecules

57
Q

When does dilatant flow occur?

A

When viscosity increases with the rate of shear

58
Q

What is dilatant flow also known as?

A

Shear thickening

The opposite of pseudo plastic flow

59
Q

What causes dilatant flow?

A

Dispersions containing a high concentration of small, deflocculated particles

MPharm 2 - PH2107 (26 decks)

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