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SIU 1 GIT > Solubility, Dissolution Rate > Flashcards

Solubility, Dissolution Rate Flashcards

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1
Q

Define solution

A

Molecular dispersion formed by two or more components which form a ONE PHASE HOMOGENOUS system
Can be applied to solid liquid and gas (micelles?)

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2
Q

Define saturated solution

A

Solute in liquid phase is in equilibrium with the solid phase (solute)

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3
Q

What is the rate limiting step in dissolution? What factors affect it?

A

The diffusion of solute across the saturated boundary layer
Fick’s law
J=DAK (Cs-C)/h
K partition coefficient

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4
Q

How to calculate the diss R constant k? What’s the unit?

A

K= D/V x h
D: diffusion coefficient
V: vol of solvent
h: thickness of saturated layer

Unit: length^-2 or time^-1

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5
Q

The influence of temp on solubility of NaSO4 10H2O (sodium sulphate decahydrate)

A

Sol increase w temp up to 32.5C
Dissociation in water = endo, favoured as temp increases.
At 32.5C, converts to anhydrous form-transient temp
Solubility decrease with temp
dissolution = exo, NOT favoured as temp increases. Reduced exo/diss/ sol

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6
Q

If the MP of sulphonamide derivatives increases, what you expect for the change in sol?

A

Decrease in Solubility

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7
Q

Reduced aqueous sol, by esterification of parental drug is suitable for which drug?

A

Mask the taste
1 Chloramphenicol palmitate instead of chloramphenicol base
For paediatric suspension
2 Protect from GI degradation/facilitate absorption: erythromycin propionate (less soluble so less readily degraded, more readily absorbed) instead of erythromycin

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8
Q

How does polymorphism occur and what are its impacts on solubility

A

Occurs during salt (of drug) crystallisation-
molecules/ions arranged differently in the lattice.

Form I : STABLE polymorph -stable,higher Mp, LESS soluble

Form II: METAstable polymorph- less stable, lower Mp, MORE soluble

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9
Q

Examples of cosolvent

A

Ethanol, glycerol, propylene glycol

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10
Q

Define cosolvent

A

Solvents that in combination, increase the solubility of the solute

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11
Q

Define cosolvency

A

Phenomenon which a solute is more soluble in mixture of solvent than in one alone

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12
Q

Some solid cosolvent which are highly soluble in water

A

PEG, PVP, urea

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13
Q

Describe the relationship between sigma and the polarity of the cosolvent (for non polar solute)

A

Greater the sigma, lower the polarity of solvent

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14
Q

What’s the effect of cosolvent on water with non polar/ semi polar solute?
What’s that of cosolvent on water with polar solute

A

Increase the solubility of nonpolar solute in water
Cosolvency decreases as solute becomes more polar
Decrease sol of polar solute

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15
Q

What’s sigma stands for

A

The effectiveness of a cosolvent as a solubiliser for a particular solute

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16
Q

Classification of surfactants

A

Charge carried by the polar part

  • anionic
  • cationic
  • non ionic
  • zwitterionic -both +,-ve
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17
Q

What’s POE

A

Polyoxyethylene chains
Is non ionic surfactant
Hydroxy + ether groups (non polar moiety) need more units to give polar moiety

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18
Q

Anionic surfactant

  • ad
  • disad
  • application
A

Cheap, widely used
Toxicity, external use only
O/W emulsifier

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19
Q

Cationic surfactant

  • ad
  • disad
  • application
A

Disinfectant, preservative properties
Toxicity
O/W emulsifier

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20
Q

What makes nonionic surfactant a better option?

  • ad
  • application
A

Low toxicity
Low irritancy
Oral and parental use
O/w w/o emulsifier

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21
Q

What’s Kappa

A

Molar solubilisation capacity :the number of moles of solute that can be solubilised by 1 mole of micelles surfactant

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22
Q

Increase chain length by 2 carbons will decrease the sol by how much?

A

10 folds!

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23
Q

In practice, what chain length of surfactant do we use

Meet what criterias

A

12-16 C or 18C with double bond(eqv to decrease chain length)
Provides LOW cmc, sufficient water SOLUBILITY for drug

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24
Q

Less polar solution has a …. surface tension

Why? (Inc surfactant)

A

Lower
Less H bond bw neighbouring molecules, more interactions with the air, more volatile
Longer Hc chain- non polar- tendency adsorbing onto surface - disturb the tight arrangement of molecules- lower surface tension

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25
Q

Lundelius’s rule

A

Factor that decreases solubility of surfactant, increases the surface activity

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26
Q

Phase inversion temp

  • what type of surfactant
  • stabilise what type of emulsions at what temperature
  • relate to cloud point
  • definition
A

For NON ionic surfactant
Stabilise o/w at low Temp- surfactant is water soluble
Stabilise w/o at high temp -oil soluble
The temperature at which emulsifier changes from being an o/w to w/o emulsifier

27
Q

Describe the DLVO theory about pharmaceutical suspension

A

When dispersed in a liquid medium, particles will experience electrostatic repulsive force and attractive VDW forces
The energy of both equals to Vt the overall energy of interaction between particles

28
Q

What does it mean by caking in pahrameacetical suspension

A

Irreversible coagulation, not able to re-disperse upon shaking

29
Q

What’s Zeta potential

A

Measures degree of electric charge on particles relative to bulk medium ( in which they are suspended

30
Q

How to compress the electrical double layers to stablise pharmaceutical suspension

A

Increase concentration of electrolyte

31
Q

The are the assumptions in stokes equation

A
  1. Spherical particles of uniform size
  2. Dilute suspension medium < 2% w/v
  3. No interactions between particles and suspension medium
32
Q

What is the stocks equation

A 
The rate of sedimentation 
v = 2 x a^2 x g (Pp-Pm) / 9 x n
a: particle radius. Smaller the size, harder to form caking 
g: gravity 
Pp: density of particles 
Pm: density of medium 
n: viscosity of suspension medium. The higher the viscosity, the slower the sedimentation. 
Easier to sediment in dilute liquid
33
Q

How to reduce the rate of sedimentation

A

Reduce particle diameter

Increase viscosity of vehicle

34
Q

How to calculate the sedimentation volume

A

F= Vs / Vi
Vs: volume of sediment
Vi: initial volume of whole suspension

35
Q

What the desired state of a suspension formulation

A

To achieve partial or controlled flocculation (weakly attracted)

36
Q

2 methods of performing assessment of the sedimentation of drug suspension

A
  1. Sedimentation volume

2. Degree of flocculation

37
Q

What’s degree of flocculation

A

Ratio of the ultimate sedimentation volume (h sed) of the flocculated suspension to the ultimate sedimentation volume of the deflocculated suspension

38
Q

How to manipulate the magnitude of the secondary minimum for a suspension which has high Zeta potential (primary max)

A

Addition of electrolyte
Or
Charged surfactants
So that more stable

39
Q

4 criteria for acceptable suspension

A
  1. Low rate of sedimentation
  2. Disperse phase: re-disperse upon shaking
  3. Flow properties: formulation easily removed from the container
  4. Aesthetically pleasing (looks)
40
Q

How to prevent small particles dissolve then crystallise onto surface of larger particles (increase in temp then decrease during storage

A

Hydrophilic polymers reduced crystal growth by adsorption onto particles for protection

41
Q

What are the excipients added to control sedimentation and physically stabilise the suspension

A

1.Addition of electrolytes: reduced Zeta potential, not to be primary max
2.Surface active agents: wetting, reduce interphase tension, less likely to aggregate
Non ionic is preferred: POE, sorbitan ester, lecithin
Ionic: greater toxicity
3. Addition of hydrophilic polymers: increase viscosity, reduce rate of sed, increase stability
Polymer C
Affects flow

42
Q

Hydrophilic polymers examples

A

Cellulose derivatives: methylcellulose, hydroxyethylcellulose,
HPMC

PVP
sodium alginate 
Acacia, tragacanth (gum) 
PolymerC 
Hydrated silicates
43
Q

What’s the acceptable size of particle?

A

0.5-100 micrometer

<0.5 colloid

44
Q

What’s an emulsion

A

Disperse system in which an insoluble liquid (disperse phase) is dispersed in a second liquid (continuous phase)

45
Q

Advantages of pharmaceutical emulsions

A
  1. Delivery of drug with low aqueous solubility (drug can be dissolved in oil phase o/w)
  2. Taste masking, sweetener in continuous phase
  3. Oils in o/w with therapeutic effects (catheritic- cleansing)
  4. Reduce irritation by drug after topic administration
  5. Difficulty swallowing
  6. Parental nutrition
46
Q

Disadvantage of emulsions

A

Thermodynamically unstable, may separate into two phases

Emulgents are hard to manufacture

47
Q

What’s a multiple emulsion (w/o/w)

A

2 phases for the disperse phase

48
Q

Define cracking in emulsion

A

Irreversible instability
Complete coalescence of internal phase resulting in separation of emulsion into two layers
Destruction of film at interface

49
Q

What’s the cause of creaming

A

The density difference between oil and water phases (want it to be zero- stocks equation)

50
Q

What’s creaming

A

Either sedimentation or elevation of droplets of internal phase producing a layer of concentrated emulsion either at top or bottom of container

Homogenous upon shaking

51
Q

How to reduce the rate the creaming

A

Smaller particles size

Increase viscosity of emulsion

52
Q

What is the critical phase volume ratio for o/w and w/o to allow phase inversion when exceed

A

O/w 75:25

W/o 40:60

53
Q

What type of film is surfactant (interphase of disperse and external phase)

A

Mono molecular

54
Q

How to determine type of emulsion when adsorbed particles are used

A

Depends on preference of particles for each phase

If wetted preferentially by aqueous phase then o/w

55
Q

Example of adsorbed particles used in o/w and w/o

A

AlOH3,MgOH2, kaolin

Talc, carbon black

56
Q

Surfactant in emulsions

Lanolin

A

Sheep wool fat
W/o
Ointment
Emollient

57
Q

Surfactant in emulsions

Lanolin alcohol

A

W/o
Cream water absorptive
Prone to oxidation - antioxidant

58
Q

Surfactant in emulsions

An ionic emulsifying wax

A

O/w
Cream when 10%w/w high wax conc
TOPICAL

59
Q

Surfactant in emulsions

Non ionic emulsifying wax

A

Higher conc for stability 15-25%

Tolerant to electrolytes

60
Q

Surfactant in emulsions

Beewax

A

Mix of esters of monohydric alcohol and straight Chain acid Long chain
Component : myricyl palmitate
Increase consistency of cream

61
Q

Is each phase (in emulsion) formulated separately or together

A

Separately
Vehicle- purified water
Buffer
Oil- veg oil, almond oil etc

62
Q

Manufacturing steps of emulsion /cream

A

Dissolution of oil double components oil phase
Dissolution of water soluble compo. Aqueous phase
Turbulent mixing condition
Emulsions :
Lab scale- mechanical stirrer
Production scale- mechanical stirrer homogeniser, ultrasonifers, colloid mills

63
Q

The optimum phase to volume ratio for emulsion is

A

50:50

SIU 1 GIT (7 decks)

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