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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
Lundelius's rule
Factor that decreases solubility of surfactant, increases the surface activity
26
Phase inversion temp - what type of surfactant - stabilise what type of emulsions at what temperature - relate to cloud point - definition
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
Describe the DLVO theory about pharmaceutical suspension
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
What does it mean by caking in pahrameacetical suspension
Irreversible coagulation, not able to re-disperse upon shaking
29
What's Zeta potential
Measures degree of electric charge on particles relative to bulk medium ( in which they are suspended
30
How to compress the electrical double layers to stablise pharmaceutical suspension
Increase concentration of electrolyte
31
The are the assumptions in stokes equation
1. Spherical particles of uniform size 2. Dilute suspension medium < 2% w/v 3. No interactions between particles and suspension medium
32
What is the stocks equation
``` 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
How to reduce the rate of sedimentation
Reduce particle diameter | Increase viscosity of vehicle
34
How to calculate the sedimentation volume
F= Vs / Vi Vs: volume of sediment Vi: initial volume of whole suspension
35
What the desired state of a suspension formulation
To achieve partial or controlled flocculation (weakly attracted)
36
2 methods of performing assessment of the sedimentation of drug suspension
1. Sedimentation volume | 2. Degree of flocculation
37
What's degree of flocculation
Ratio of the ultimate sedimentation volume (h sed) of the flocculated suspension to the ultimate sedimentation volume of the deflocculated suspension
38
How to manipulate the magnitude of the secondary minimum for a suspension which has high Zeta potential (primary max)
Addition of electrolyte Or Charged surfactants So that more stable
39
4 criteria for acceptable suspension
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
How to prevent small particles dissolve then crystallise onto surface of larger particles (increase in temp then decrease during storage
Hydrophilic polymers reduced crystal growth by adsorption onto particles for protection
41
What are the excipients added to control sedimentation and physically stabilise the suspension
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
Hydrophilic polymers examples
Cellulose derivatives: methylcellulose, hydroxyethylcellulose, HPMC ``` PVP sodium alginate Acacia, tragacanth (gum) PolymerC Hydrated silicates ```
43
What's the acceptable size of particle?
0.5-100 micrometer | <0.5 colloid
44
What's an emulsion
Disperse system in which an insoluble liquid (disperse phase) is dispersed in a second liquid (continuous phase)
45
Advantages of pharmaceutical emulsions
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
Disadvantage of emulsions
Thermodynamically unstable, may separate into two phases Emulgents are hard to manufacture
47
What's a multiple emulsion (w/o/w)
2 phases for the disperse phase
48
Define cracking in emulsion
Irreversible instability Complete coalescence of internal phase resulting in separation of emulsion into two layers Destruction of film at interface
49
What's the cause of creaming
The density difference between oil and water phases (want it to be zero- stocks equation)
50
What's creaming
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
How to reduce the rate the creaming
Smaller particles size | Increase viscosity of emulsion
52
What is the critical phase volume ratio for o/w and w/o to allow phase inversion when exceed
O/w 75:25 | W/o 40:60
53
What type of film is surfactant (interphase of disperse and external phase)
Mono molecular
54
How to determine type of emulsion when adsorbed particles are used
Depends on preference of particles for each phase | If wetted preferentially by aqueous phase then o/w
55
Example of adsorbed particles used in o/w and w/o
AlOH3,MgOH2, kaolin | Talc, carbon black
56
Surfactant in emulsions | Lanolin
Sheep wool fat W/o Ointment Emollient
57
Surfactant in emulsions | Lanolin alcohol
W/o Cream water absorptive Prone to oxidation - antioxidant
58
Surfactant in emulsions | An ionic emulsifying wax
O/w Cream when 10%w/w high wax conc TOPICAL
59
Surfactant in emulsions | Non ionic emulsifying wax
Higher conc for stability 15-25% | Tolerant to electrolytes
60
Surfactant in emulsions | Beewax
Mix of esters of monohydric alcohol and straight Chain acid Long chain Component : myricyl palmitate Increase consistency of cream
61
Is each phase (in emulsion) formulated separately or together
Separately Vehicle- purified water Buffer Oil- veg oil, almond oil etc
62
Manufacturing steps of emulsion /cream
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
The optimum phase to volume ratio for emulsion is
50:50

SIU 1 GIT (7 decks)

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