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Acid – Base
 Most drugs are weak acids or weak bases.
 An Acid is any substance that release a Hydrogen Ion( proton
donor).
 A Base is any substance that can accept a Hydrogen Ion(proton
acceptor).
 PH is a measure of acidity <7
 PH is a measure of alkalinity >7
Weak vs. Strong Acids and Bases
 Stronger means complete dissociation in water.
 Weak means incomplete dissociation in water .
Lipophilic ( fat soluble)
Hydrophilic (water soluble)
Acid/Base conjugate
 Conjugate acid compound formed when an base gains a
hydrogen ion.
 Conjugate base compound formed when an acid loses a
hydrogen ion.
Ka &PKa
 The equilibrium between unionized and ionized forms by the
acidity constant Ka(the acid dissociation constant) .
 The PKa is the negative logarithm of Ka.
PKa= - log 10 Ka
 For an acid
A General rule for determining a chemical is
strong or weak acid or base
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PKa <2: strong acid ,
PKa 4 to 6 : weak acid , weak conjugate base
PKa 8 to 10: very weak acid; conjugate base getting stronger
PKa > 12: essentially no acidic properties in water; strong
conjugate base
 The Higher Ka the stronger acid and the lower Ka weaker acid
.
Henderson–Hasselbalch equation
 In chemistry, the Henderson–Hasselbalch equation describes
the derivation of pH as a measure of acidity (using pKa, the
negative log of the acid dissociation constant).
Examples of calculations
1. What is the ratio of ephedrine to ephedrine HCl (PKa 9.6) in
the intestinal tract at PH 8.0?
2- What is the PH of buffer containing 0.1M acetic acid (PKa 4.8)
and 0.8M sodium acetate ?
Percent Ionization
 Using the drugs PKa, the formulation or compounding
pharmacist can adjust the PH to ensure maximum water
solubility(ionic form of the drug) or maximum solubility in non
polar media(un-ionic form).
 Acids can be divided in two types.
1-
2-
HA acids include :


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Inorganic acids (HCl , H2SO4)
Enols (barbiturate , hydantoins)
Carboxylic acids( low M.wt organic acids, salicylic acids)
Amides and imides
BH+ acids include :
 They are all protonated amines .
A Polyfunctional drug can have several PKa
Amoxicillin's ionic state at physiological PH 7.4
Calculations
What is the percentage ionization of ephedrine HCl (Pka 9.6) in
an intestinal tract buffered at PH 8?
 What is the percentage ionization of indomethacin (Pka 4.5)
in an intestinal tract buffered at PH 8?
PH vs.PKa?
PH= PKa
 When the PH=PKa , the compound is 50% ionized (or 50% unionized).
 When the PKa =PH , the molar concentration of the acid
equals to molar concentration of its conjugate base.
 When log ⌊conjugate base⌋/[acid] =1
Phenytoin
Tropicamide
Drug Distribution and PKa
 Acid drugs – become more NON ionized in acidic PH.
 Base drugs - become more NON ionized in alkaline PH
The main reason most acidic drugs absorbed from the intestinal
tract rather than the stomach is that microvilli of intestinal mucosa
provide a large surface area relative to that found in the gastric
mucosa of the stomach
Passage of HA acids through lipid barriers
Passage of BH+ acids through lipid barriers
Summary
 The higher Ka the stronger acid and the lower Ka weaker acid .
 The lower Pka the stronger acid and the higher Pka weaker
acid .
 The stronger acid weaker conjugate base, the weaker acid
higher conjugate base.
Home work
1. Why is Phenol considered corrosive to the skin , whereas
ephedrine HCl or free ephedrine is considered innocuous
when applied to the skin ?