L13 - Suspension - Liquid Phase Interactions

Question 1

what is needed for solid material to dissolve

Answer 1

• will not dissolve unless liquid phase has some chemical similarities

Question 2

what appens when hydrophoibc drugs are dispersed in water

Answer 2

• very low aqueous solubility
  
  • their biological target is often a hydrophobic receptor
• once dispersed in water, drug particle will acquire a charge

Question 3

what causes the charge on the particle

Answer 3

• ionisation of water
  
  • H₂O ⇌ H⁺ + OH^-
  • H⁺ + H₂O ⇌ H₃O⁺

Question 4

What are the most mobile of the ionic products of water

Answer 4

• H⁺ > OH^- (hydroxide ion) > H₃O⁺ (hydronium ion)

Question 5

describe the electric double layer for a single particle

Answer 5

• hydroxide ions collect on the surface of particle which gives it an apparent negative charge
• ovaerall the neutrlity of the system is maintained
• so gradiation of charge
  
  • -ve n particle surface (fixed)
  • +ve (diffuse) Grouy-Chapman Layetr

Question 6

why do most particles dispersed in water acquire a negative charge

Answer 6

perferential adsorption of hydroxyl ions

Question 7

describe the graph for the conc of hydroxide ions and positive ions

Answer 7

Question 8

What are the factors that affect the electrical double layer

Answer 8

• location of added materials n the electrical double layer of a single solid particle
• excipients ca change the beahvoir of solid particles in suspension (fixed layer, diffuse layer, or noth)
• examples
  
  • NaCl at low conc (0.01M) - diffuse layer
    
    • easier neutralisation of remaining surface charge on particle
  • NaCl at high conc (0.1M) - diffuse and fixed layer

Question 9

What does the DVLO theory of collodial stability state

Answer 9

• stability of hydrophobic suspension
• collodial systems - multple articles
• interaction between particle are additive (V_T)
  
  • electrical repulsion (V_R)
  • van der Waals attraction (V_A)
  • V_T = V_A + V_R

Question 10

What are the repulsive and attractive forces

DVLO theory of collodial stability

Answer 10

• repilsive
  
  • osmotic effects due to overlaps of the diffuse parts of electrical double layer
• attractive forces
  
  • van der Waals and universal forces of attraction

Question 11

What the the DVLO allow us to do

Answer 11

• predict whether suspension will coalesce and settle or remain sdispesed

Question 12

what are the characteristic of the primary minimum

Answer 12

• attractive forces > kinetic energy
• particles show
  
  • initally floculation, loosely attract but still independeant
  • then, coagulation, particles collid to form larger particles
• undesireable behaviour for pharmacetical suspensions

Question 13

What are the characteristics of the primary maximum

Answer 13

• replsive forces > attractive forces
• particles show
  
  • defloculation, remain seperated
• consider KE of particle, KE increases with temp
• V_T > KE
  
  • as a result particles move apart and V_T increase
• however
  
  • sufficient KE → overcome V_T barrier → move closer
• risky for pharmaceutical suspensions

Question 14

What are the characteristics of the secondary minimum

Answer 14

• attractive forces > repulsive forces
• particles show
  
  • limited attract to eachother and behave as “floccules”
    
    • i.e. loose aggregates of individual particles
• V_T > KE
  
  • result: particles move closer together but will not collide and coalesce as V_T is small
• As V_T incfreases, particles will experience weak repulsive forces

desireable

Question 15

how is particle behaviour controlled in suspensios

wgat is constant and varied

Answer 15

• constant
  
  • particulate material (drug)
  • continuous phase (water because formulation for oral administration)
• variable
  
  • distance of particles (partly dependant on temp - KE and particle conc)
  • surface potential of particle (can be modified by adsorbing material onto particle)
  • ionic strength
• radius of particles, e.g. V_A, V_R, and V_T are directly proportional to particle size
• changes in size influences KE → impacts overall performance

Question 16

descorbe particle movement in suspensions

Answer 16

• always some movement
• Browniam motion (relevant for particles upto a size of 1 to 2µm)
  
  • diffusion of particles improves dosage uniformity
  • important of deflocculated suspension of particles in submicrn rnage
• sedimentation
  
  • relevant for particles > 0.5µm

Question 17

stokes equation

what do the terms mean

Answer 17

Question 18

is coagulation reversible

when does it occur

Answer 18

no

primary minimum

Question 19

how can particle movement in suspension be reduced and therefore sedementation be reduced

Answer 19

• change desniy of medium ( continuous phase)
  
  • e.g. addition of dextrose
• viscosit of medium (continuous phase
  
  • e.g. addition of hydroxypropyl methyl cellulose

Question 20

what happens if the continuous phase is too viscous

Answer 20

• difficult to pour/measure dose
• changes in particular dispersion pattern
  
  • e.g. particles in primary minimum, coagulation →cannot be corrected

Question 21

what are the advatnages of a flocculated system and what are the consideration

Answer 21

easy to disperse and dose

shake bottle