Measurements of dissolution profiles (solubility):

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• Measurements of dissolution profiles
  (solubility)
• Finely divided powder of known , uniform particle
  size in excess is suspended in water and stirred
  continuously.
• Samples are taken at time intervals and filtered
  to remove any undissolved drug, then analysed to
  determine concentration of dissolved drug.
• Plot Ct against time of sampling
• When all of the drug is dissolved i.e., solution
  is saturated with drug the drug concentration
  will not change as a function of time any
  further.

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• Measurements of dissolution profiles
  (solubility)

Cs
Concentration
mg/ml
Time (hr)
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• Solubility Product
• For slightly soluble electrolytes (eg AgCl
  Al(OH)3) dissolved in water to form saturated
  solutions, their solubility is referred to as
  solubility product (Ksp).
• Formation of saturated aqueous solution is an
  equilibrium process
• AgCl (solid) Ag
  Cl-
• Ag Cl-
• K
• AgCl solid
• AgCl solid is considered constant because there
  is always some solid present.
• K Ag Cl-
• Ksp Ag Cl-
• Ksp is solubility product

K
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• Example
• A saturated solution of AgCl in water at 20oC has
  a concentration of 1.12X10-5 M of AgCl ie., Cs of
  AgCl 1.12X10-5 M.
• Calculate the solubility product Ksp.
• Ksp Ag Cl-
• Ksp (1.12X10-5 ) (1.12X10-5 ) 1.25 X 10-10
• For salts that the cations and anions have
  different number of charges e.g., Al(OH)3 you
  have to raise each concentration to a power
  corresponding to the stoichiometric number of
  ion.
• Al(OH)3 (solid)
  AL3 3OH-
• Ksp AL3 OH-3
• In general, More Ksp means more solubility

K
5

• II. Effect of Salts on solubility of solid in
  liquid
• Common ion effect
• a) Salting out
• AgCl (solid) Ag
  Cl-
• If an ion common with Ag or Cl- is added to the
  solution of AgCl (eg. NaCl), the equilibrium will
  be shifted towards the left and more AgCl will
  precipitate leading to reduced solubility.
• b) Salting in
• When the added common ion makes a complex with
  the salt whereby the net solubility is increased
  because solubility of new salt is more than
  solubility of AgCl.

K
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Energetics of SolubilitySolubility and heat of
solution

• Solubility as a function of temperature for non
  electrolytes or weak electrolytes or strong
  electrolytes in non ideal solution can be
  calculated according to the equation
• ln (C /C- )
• Where C is concentration at temperature two
• C- is concentration at temperature one
• ?H solution is heat of solution (Cal/
  mol) and defined as heat gained when one
  mole of solute is dissolved in solvent
• R is universal gas constant (1.9872 Cal/
  mol.deg)
• T is temperature two in Kelvin Co 273
• T- is temperature one in Kelvin Co 273

(T - T-)
?H solution
X
R
(T T-)
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• Non electrolytes
• Substances that do not yield ions when dissolved
  in water and therefore do not conduct an electric
  current through the solution e.g., sucrose or
  glycerin in water
• Strong electrolytes
• Substances that yield ions by completely ionizing
  in water when dissolved in water leading to
  strong conduction of electric current. e.g.,
  hydrochloric acid and sodium sulfate.
• Weak electrolytes
• Substances that yield ions by partially ionizing
  in water when dissolved in water leading to weak
  conduction of electric current. e.g., ephedrine
  and phenobarbital.
• Ideal solution
• A solution where contribution of different
  components in a liquid mixture to vapour pressure
  is according to the molar fraction of the
  different components.

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• Example
• The solubility of urea (Mwt. 60.6 gm/ mol) in
  water at 25oC is 1.20 gm/ gm water. The ?H
  solution for urea in water at 25oC is 2820 Cal/
  mol. What is solubility in gm/ gm and the molal
  solubility at 5oC.
• Solubility in gm/ gm at 5oC is unknown
• T- 5 273 278 oK
• T 25 273 298 oK
• ?H solution 2820 Cal/ mol
• C 1.20 gm/ gm
• R 1.9872 Cal/ deg. Mol
• C- ?
• ln (C /C- ) (?H / R) X (T - T- ) / (T T-)
• lnC- ln C- (?H / R) X (T - T- ) / (T T-)
• lnC- (?H / R) X (T - T- ) / (T T-) ln C-

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• Example
• The solubility of urea (Mwt. 60.6 gm/ mol) in
  water at 25oC is 1.20 gm/ gm water. The ?H
  solution for urea in water at 25oC is 2820 Cal/
  mol. What is solubility in gm/ gm and the molal
  solubility at 5oC.
• lnC- (?H / R) X (T - T- ) / (T T-) ln C-
• Ln1.2-(2820/1.9872)X(298-278 )/(298x278)) ln
  C-
• ln C- -0.161
• C- 0.851 gm/gm
• the molal solubility at 5oC is unknown.
• C- 0.851 gm/gm 851 gm/kg
• Number of moles weight / mol. Weight
• Number of moles 851 gm / 60.6 gm / mol14.04
• Molal solubility 14.04 mol/kg
• Solubility at 5oC 0.851 gm/ gm
• Solubility at 25oC 1.2 gm/ gm

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Thank you