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08/05/18BHARDWAJ CLASS
08/05/18
2
 pH is the logarithm of hydrogen and hydroxyl ion
concentration.
 pH scale is present between 0 to 14.
ACIDIC BASIC
BHARDWAJ CLASS
08/05/18
3
 pKa is the negative logarithm of the dissociation constant of a drug.
 According to Henderson -Hasselbalch equation –
pH = pKa – log ( ionized/unionized)………..for a weak acid.
pH = pKa – log ( unionized/ionized)………...for a weak base.
pH = pKa – log ( ionized/unionized)………… .1
when ionized = unionized
equation change into
pH = pKa – log ( 1/1)………………….2
Or pH = pKa – log 1 (log 1 = 0)
pH = pKa ………………………………3
From the equation 3 the pKa is Ph where the ionized part is equal to
unionized part.
BHARDWAJ CLASS
08/05/18
4
MOST DRUG MOLECULES ARE EITHER WEAK ACIDS OR WEAK BASES.
Very weak acidic drug (pKa>8) e.g. is pentobarbitol ,hexobarbitol.
Strong acidic drug (pKa <2.5) e.g. is disodium cromoglycate.
BHARDWAJ CLASS
08/05/18
5
This theory given by Brodie et.al.
This is based on the assumption that the gastrointestinal /blood barrier acts as a
lipid Barrier toward weak electrolyte drugs which are absorbed by passive
diffusion. The gastrointestinal /blood barrier is permeable to the non-ionized
drug form and impermeable to ionized form.
Thus process of absorption is depend on THE IONIZAION AND
UNIONIZATION STATE OF DRUG.
BHARDWAJ CLASS
08/05/18
6
According to Henderson -Hasselbalch equation –
pH = pKa – log ( ionized/unionized)………..for a weak acid.
pH = pKa – log ( unionized/ionized)………...for a weak base.
Example – calculate the part of drug absorption of drug having pKa
4.
Solution – if the drug have pKa = 4
In gastric fluid (where ph is in the range of 2 to 4.) and in blood
(Ph=7.4)
In gastric fluid (assume that pH is 1.2)
pH = pKa – log ( ionized/unionized)………..for a weak acid
1.2 = 4- log (ionized/unionized)
1.2-4 = log (ionized/unionized)
-2.8 = log (ionized/unionized)
Antilog (-2.8) = (ionized/unionized)
BHARDWAJ CLASS
08/05/18
7
Example – calculate the part of drug absorption of drug having pKa 4.
Solution – if the drug have pKa = 4
In gastric fluid (where ph is in the range of 2 to 4.) and in blood (Ph=7.4)
pH = pKa – log ( ionized/unionized)………..for a weak acid
STOMACH pH=1.2 BLOOD (Ph=7.4)
ionized ionizedunionized unionized
BHARDWAJ CLASS
08/05/18
8
BHARDWAJ CLASS

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Ph hypothesis

  • 2. 08/05/18 2  pH is the logarithm of hydrogen and hydroxyl ion concentration.  pH scale is present between 0 to 14. ACIDIC BASIC BHARDWAJ CLASS
  • 3. 08/05/18 3  pKa is the negative logarithm of the dissociation constant of a drug.  According to Henderson -Hasselbalch equation – pH = pKa – log ( ionized/unionized)………..for a weak acid. pH = pKa – log ( unionized/ionized)………...for a weak base. pH = pKa – log ( ionized/unionized)………… .1 when ionized = unionized equation change into pH = pKa – log ( 1/1)………………….2 Or pH = pKa – log 1 (log 1 = 0) pH = pKa ………………………………3 From the equation 3 the pKa is Ph where the ionized part is equal to unionized part. BHARDWAJ CLASS
  • 4. 08/05/18 4 MOST DRUG MOLECULES ARE EITHER WEAK ACIDS OR WEAK BASES. Very weak acidic drug (pKa>8) e.g. is pentobarbitol ,hexobarbitol. Strong acidic drug (pKa <2.5) e.g. is disodium cromoglycate. BHARDWAJ CLASS
  • 5. 08/05/18 5 This theory given by Brodie et.al. This is based on the assumption that the gastrointestinal /blood barrier acts as a lipid Barrier toward weak electrolyte drugs which are absorbed by passive diffusion. The gastrointestinal /blood barrier is permeable to the non-ionized drug form and impermeable to ionized form. Thus process of absorption is depend on THE IONIZAION AND UNIONIZATION STATE OF DRUG. BHARDWAJ CLASS
  • 6. 08/05/18 6 According to Henderson -Hasselbalch equation – pH = pKa – log ( ionized/unionized)………..for a weak acid. pH = pKa – log ( unionized/ionized)………...for a weak base. Example – calculate the part of drug absorption of drug having pKa 4. Solution – if the drug have pKa = 4 In gastric fluid (where ph is in the range of 2 to 4.) and in blood (Ph=7.4) In gastric fluid (assume that pH is 1.2) pH = pKa – log ( ionized/unionized)………..for a weak acid 1.2 = 4- log (ionized/unionized) 1.2-4 = log (ionized/unionized) -2.8 = log (ionized/unionized) Antilog (-2.8) = (ionized/unionized) BHARDWAJ CLASS
  • 7. 08/05/18 7 Example – calculate the part of drug absorption of drug having pKa 4. Solution – if the drug have pKa = 4 In gastric fluid (where ph is in the range of 2 to 4.) and in blood (Ph=7.4) pH = pKa – log ( ionized/unionized)………..for a weak acid STOMACH pH=1.2 BLOOD (Ph=7.4) ionized ionizedunionized unionized BHARDWAJ CLASS