SATURATED SOLUBILITY OF BENZOIC ACID

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SATURATED SOLUBILITY OF BENZOIC ACID
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Solubility It is the concentration of a solute
in a saturated solution at a certain temperature

• Classification of solutions (Based on amount of
  solute)
• Subsaturated Solutions
• Saturated Solutions
• Super-Saturated Solutions

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There are three types of solutions (Based on
nature of solute and solvent)
Gas/ liquid
Liquid/ liquid
Solid/ liquid
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Solubility is affected by

• Temperature
• Type of Solvent
• pH
• Particle size
• Molecular Structure
• Crystal Structure
• Added Substance e.g. electrolytes.

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Determination of Solubility

• This comes in two steps
• Preparation of saturated solution
• Analysis of saturated solution according to the
  nature of the drug

Evaporation method
Volumetric method
Gravimetric method
Instrumental method
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Experiment 5

• Determination of Solubility of Benzoic acid and
  effect of added salt

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Calculation of of NaCl added

• NaCl was added to a volume of 25 ml of the
  filtrate.
• e.g. Conc. Of NaCl 1X100/25 4

1 gm
25 ml
?
100ml
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Salting out Effect
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Calculation

• Determination of saturated solubility of benzoic
  acid
• N.V N.V

Normality of benzoic acid
Volume of sample(5ml)
mls of titrant
Normality of NaoH(0.1N)
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N N.V/ VN (0.1).V/ 5Solubility of
benzoic acid (gm/L) N. E
Equivalent weight of benzoic acid 122
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• (grams)
• N x E
  1000 ml
• ?
  100 ml
• Conc of benzoic N . E . 100/1000
• ..............gm/100ml
  

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Table (A)
Sample Number Temperature Burette reading Burette reading Volume of 0. IN NaOH required for neutralization (b - a) mL
Sample Number Temperature Initial reading (a) Final reading (b) Volume of 0. IN NaOH required for neutralization (b - a) mL
1 2 3 Room Temp. (-----C)
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2. Calculation of Conc. Of Benzoic acid in
presence of NaCl

• N.V N.V
• N N.V/V
• (0.05). V/5
• Concentration of benzoic acid (g/l) N.E
• Concentration of benzoic acid (g/100ml)
• N.E . 100/ 1000

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Table (B)
Sample Amount of Volume of Burette reading Burette reading Volume of Solubility
Number Electrolyte Solution Initial Final () w/v
added (g) Titrated reading reading NaOH
(ml) Used
1. 0 5
2. 1 5
3. 2 5
4. 3 5
5. 4 5
6. 5 5
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Plot dissolved benzoic acid against of added
NaCl
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PRECAUTIONS

• Titration with the correct Titrant
• 0.1 N NaOH for benzoic acid in absence of
  electrolyte.
• 0.05 N NaOH for benzoic acid in presence of
  electrolyte.
• The graph (best fitting line) must intercept the
  Y axis at saturated solubility of benzoic at 0
  electrolyte.

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Effect of pH on Solubility

• Weak acids better dissolve at high pH (basic
  medium), e.g. phenobarbital
• Weak bases better dissolve at low pH (acidic
  medium), e.g. Atropine
• For weak electrolytes
• HP H P H
  P-
• dissolved dissolved
• (molecular) (ionized)

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Equations of weak acids and bases

• Weak acid
• S or Sttotal solubility of weak acid in the
  medium.
• S0 or Kswater solubility of weak acid (unionized
  form).
• Kadissociation constant of free acid.

• Weak base
• S or Sttotal solubility of weak base in the
  medium.
• S0 or Kswater solubility of weak base (unionized
  form).
• Kbdissociation constant of free base.
• Kwdissociation constant of water.

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Expression Terms

• Total solubility (S)
• 1- Molar concentration or
• (Initial molar concentration)
• 2- Total solubility
• 3- Initial concentration.
• 4- Solubility of dissociated undissociated
  forms.

• Water solubility (S0)
• 1-Molar solubility.
• 2- Solubility or water solubility.
• 3- Ks
• 4- Solubility of undissociated form.

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Problems

• 1 What must be the pH of an aqueous formulation
  be in order to maintain in solution 10 mg per ml.
  of a weakly acidic drug M. Wt 200, Ka 1 x
  l0-5 and Ks 0.00l M/L.
• Solution
• Desired molar concentration

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• 2 Below what pH will free phenobarbital begin
  to separate from a solution having an initial
  concentration of 1 g of sodium phenobarbital per
  100 ml at 25oC. The molar solubility So of
  phenobarbital is 0.005 and the pKa 7.41 at
  25oC. The molecular weight of sodium
  phenobarbital is 254.
• Solution
• The molar concentration of salt initially added
  is