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PMP-102 > 1. Stability > Flashcards

1. Stability Flashcards

1
Q

Disperse system

A

emulsion and suspension

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2
Q

If particles are less than 1 um

A

Colloidal system

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3
Q

Continuous phase

A

usually in water

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4
Q

Physical stability

A
  • Lyophobic systems have a poor interaction with the solvent
  • Suspensions are ‘coarse’ i.e. contain larger particles
  • Large particles SEDIMENT
  • Stokes’ law governs the sedimentation
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5
Q

Why physical instability can be problematic?

A
  • not mixed properly
  • uneven distribution
  • inadequate suspension
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6
Q

Why must drugs be homogenous before administration?

A
  • mixed properly
  • e.g in a vigle
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7
Q

HETEROGENOUS

A
  • drug not disbursed well
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8
Q

Second approach: Enabling re-dispersion

A
  • shake ; re-embursed
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9
Q

Instability phenomena

A

1) Aggregation
2) Coagulation
3) Flocculation
4) Sedimentation
5) Caking
6) Ostwald ripening

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10
Q

Aggregation

A

Particles in groups

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11
Q

Coagulation

A

Closely aggregated and difficult to redisperse

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12
Q

Flocculation

A

Aggregates have an open structure with particles a small distance apart, attracted by weak forces to form flocs or flakes

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13
Q

Sedimentation

A

Process of settling or being deposited as a sediment

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14
Q

Caking

A

Deflocculated particles (fine separate particles) form cakes which are difficult to re-suspend

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15
Q

Ostwald ripening

A

Dissolution of small crystals or sol particles and the re-deposition of dissolved species on the surfaces of larger crystals or sol particles

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16
Q

Stability

A

Physical instability results in poor dosing reproducibility

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17
Q

Factors affecting stability (they are interconnected):

A

Kinetic properties (motion of the particles with respect to dispersion medium)
Brownian motion and diffusion
Sedimentation
Viscosity
Size/shape
Electrical properties

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18
Q

Brownian motion and diffusion

A

Particles diffuse from a high concentration to a low concentration

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19
Q

Diffusion rate is based on Fick’s first law:

A

𝑑𝑚/𝑑𝑡=−𝐷𝐴 𝑑𝐶 / 𝑑𝑥

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20
Q

What does each letter stand for (Fick’s first law)?

A

𝑑𝑚/𝑑𝑡 = mass of substance diffusing over time
D = diffusion coefficient
A = area
𝑑𝐶/𝑑𝑥 = concentration gradient

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21
Q

Diffusion coefficient, D(Stokes-Einstein equation)

A

𝐷=(𝑘_𝐵 𝑇) / 6𝜋𝜂𝑟

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22
Q

What does each letter stand for (Stokes-Einstein equation)?

A

kB = Boltzmann constant
T = Absolute temperature
η = Viscosity of medium
r = Radius of the solute molecule

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23
Q

Bigger the solute molecule…

A

The less of diffusion rate because bigger particles cannot move as freely as smaller particles

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24
Q

Collision&raquo_space;> Aggregation

A

particles collide and come together (clusters)

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25
Q

Where else does aggregation happen outside of pharmacy?

A

Collisions of microscopic water droplets in clouds > macroscopic raindrops

Collisions of dust grains > dynamics of sand storms

26
Q

Sedimentation

A

The rate of sedimentation is dependant on the combined forces of gravity and drag

27
Q

Particle falling under the forces of gravity according to Stokes’ law

A

𝑉=(2𝑟^2×(𝜌−𝜌_o)×𝑔)/(9𝜂_o )

28
Q

If Veodity is high

A

sedimentation will be low

29
Q

What does each letter mean (Stokes’ law)?

A

v = sedimentation rate
r = particle radius
r = density of the disperse phase
ro = density of the continuous phase
g = gravity
ηo = viscosity of the continuous phase

30
Q

What does this equation cover?

A

Only applies to > 0.5 μm
If 𝜌−𝜌_o < 0 then creaming rather than caking

31
Q

Where else outside of pharmacy do we come accross sedimentation?

A

> Sediment enriches the soil withnutrients
- Areas rich in sediments are often also rich inbiodiversity

> Sedimentary soil is usually better forfarming
- Deltas and river banks, where much sediment is deposited, are often the mostfertileagricultural areas in a region

32
Q

Viscosity - no flow

A
  • Related to molecular weight of suspended particles/suspending agents
  • Resistance to flow under an applied stress
33
Q

Not just in pharmacy - Viscosity

A
  • In some instances a thicker liquid being thoughtof as superior quality when compared to a thinner product
  • Engine oil acts as a seal space between the piston & cylinder as they are not completely smooth
  • Fill gaps to optimise engine performances and efficiency

e.g - honey

34
Q

Factors influencing the rheology of suspensions

A

a) High volume fractions, f
b) Particle size
c) Particle size distribution
d) Particle shape
e) Electrostatic interactions
f) Steric hindrance

35
Q

Shape

A
  • Many suspended particles are spherical
  • Several measurement techniques assume a sphere
  • However, some are not spherical
36
Q

Small deviation

A

Ellipsoidal model

37
Q

Large deviation

A

Hydroxyapatite (rod-shaped)
Clay suspension (plate)
Polymers in solution (coil)

38
Q

Prevention of Sedimentation

A

𝑉=(2𝑟^2×(𝜌−𝜌_o)×𝑔) / (9𝜂_o )

39
Q

1) Form smaller particles
2) Decrease the density difference between the two phases
3) Increase viscosity of continuous phase

A
  • Particles still collide, but less frequently
  • Depends on the relative attractive and repulsive forces between particles
40
Q

Electrical properties

A

Most surfaces acquire charge

41
Q

Various charging mechanisms

A

Ion dissolution

(Ca2+10(PO43-)6(OH-)2) (solid) ⇌ 10Ca2+ (aq) + 6PO43- (aq) + 2OH- (aq)

42
Q

Ionisation

A

Citrate COO-

Polystyrene latex COO-

Amino acids and proteins COO- and NH3+

43
Q

Unequal ion adsorption

A

Give you a net charge on the surface

44
Q

Electrical double layer of ions

A

Stern layer
Diffuse layer

45
Q

Zeta potential = magnitude and type (+ or –) of the electrical potential at the slipping plane

A
  • Low zeta potential (0 to 5 mV) are prone to aggregate
  • Zeta potential > 30 mV tend to remain dispersed
46
Q

Zeta potential

A

Measure how the particles react with each other

47
Q

Magnitude of the zeta ^^^

A

REMAIN DISPERSED

48
Q

Low magnitude of zeta

A

Might re-imburse

49
Q

Factors affecting zeta potential

A

Ion concentration

pH of continuous phase

50
Q

Ion concentration

A

Charge of ions determines magnitude
1 carboxylate group vs 3 carboxylate groups in citrate

51
Q

pH of continuous phase

A

Alters the ionisation of ionic species in the continuous phase and the surface charge of ionisable groups

52
Q

pKa - affects if they are single, double or triple charge:

A

H3PO4⇌ H++H2PO4− (pKa1≈ 2.12)
H2PO4−⇌ H++HPO42− (pKa2≈ 7.21)
HPO42−⇌ H++PO43− (pKa3≈ 12.67)

C6H8O7 ⇌ H++C6H7O7− (pKa1≈ 3.13)
C6H7O7− ⇌ H++C6H6O72− (pKa2≈ 4.76)
C6H6O72− ⇌ H++C6H5O73− (pKa3≈ 6.40)

53
Q

DLVO (Established byDerjaguin, Landau, Verwey, and Overbeek in the 1940s)

A

VT = VA + VR

54
Q

DLVO - definition

A

Quantitative approach to the stability of lyophobic systems
Assumes the only interactions involved are
Van der Waals forces of attraction (VA)
Electrostatic repulsive forces (VR)

55
Q

recap - VDW

A

weak forces

56
Q

Electrostatic repulsive forces (VR)

A

Repulsive forces from electrical charges on particles

Ionisation of surface groups

Adsorption of ions

57
Q

EXAMPLE OF Electrical repulsion

A

A particle surface with a positive charge has a layer of negative ions attracted to its surface in the Stern layer

58
Q

DLVO graph

A
  • Secondary minimum is more important
  • Very few coarse suspensions remain suspended
59
Q

Where should you aim for to produce a redispersible coarse suspension?

A

flocculated suspnsions

60
Q

Flocculation:

A

Low energy of attraction possible - ranging not a strong coloration

61
Q

Coagulation

A

High energy of attraction possible

62
Q

Dispersed

A

High energy of repulsion - particles may remain dispersed

PMP-102 (49 decks)

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