Solubility vs pH: The solution pH has a pronounced effect on the solubility of weak acids and bases.Above the pKa for acids and below the pKa for bases,the solubility increases by a factor of 10 for every pH unit.This change in solubility with pH is important for the absorption of many drugs e.g.aspirin,motrin,naproxen. 10.00- Piroxicam Solubility @37C OH (jw/bw) 1.00- 0.10 0.01 0 2 68 10 12 pH
1.2.pH and pKa DEFINITION OF pH Arrhenius 1887 gave a definition of an acid and a base: an Acid gives rise to excess of H+in ag solution whereas a Base gives rise to excess of OH-in solution Bronsted-Lowry in 1923: a proton donor was defined as an acid and a proton acceptor as a base Lewis in 1923 who extended the concept to an Acids being an e-pair acceptor and a base a e-pair donor The pH concept was introduced in 1909 by the Danish chemist S.P.L.Sorenson: pH is defined by the negative logarithm of the hydronium ion activity. Bronsted 1943:pH is defined by the negative logarithm of the hydronium ion concentration: pH =-log10 [H3O*]
1.2. pH 1.2. pH and pKa ¾ DEFINITION OF pH DEFINITION OF pH Arrhenius 1887 gave a definition of an acid and a base: Arrhenius 1887 gave a definition of an acid and a base: an Acid gives rise to excess of H+ in an Acid gives rise to excess of H+ in aq solution whereas a Base gives rise solution whereas a Base gives rise to excess of OH to excess of OH- in solution in solution Bronsted Bronsted-Lowry in 1923: Lowry in 1923: a proton donor was defined as an acid and a proton acceptor as a a proton donor was defined as an acid and a proton acceptor as a base Lewis in 1923 who extended the concept to an Acids being an e Lewis in 1923 who extended the concept to an Acids being an e -pair acceptor and a base a e acceptor and a base a e -pair donor pair donor The pH concept was introduced in 1909 by the Danish chemist The pH concept was introduced in 1909 by the Danish chemist S.P.L.Sorenson: S.P.L.Sorenson: pH is defined by the negative logarithm of the pH is defined by the negative logarithm of the hydronium ion activity. ion activity. Bronsted Bronsted 1943: pH is defined by the negative logarithm of the 1943: pH is defined by the negative logarithm of the hydronium hydronium ion concentration: concentration: pH = - log10 [H3O+]
From Veli Pekka Tanninen, pH scale preformulation,HU, 30,01,02 pH scale 100 107 1014 Small Stomach Intestine Blood 012 34567 89 101112 1314 0 Battery Orange Acid Vinegar juice Milk Sea Water Bleach Physiological pH values: Stomach 2 Kidneys 4.2 (variable) Small Intestine Fed 5.0 Fasted 6.8 Duodenal Mucus 5.5
pH scale pH scale Physiological pH values: Stomach 2 Kidneys 4.2 (variable) Small Intestine Fed 5.0 Fasted 6.8 Duodenal Mucus 5.5 From Veli Pekka Tanninen, preformulation, HU, 30,01,02
1.2.pH and pKa 1.Definition: The pKa or 'Dissociation Constant'is a measure of the strength of an acid or a base under certain pH. Strong acids and bases defined as completely ionized in pH range 0-14 Weak acids and bases-defined as incompletely ionized in pH range 0-14 2.Significance: pKa→solubility→absorption
1.2. pH 1.2. pH and pKa 1. Definition: 1. Definition: The pKa or 'Dissociation Constant' 'Dissociation Constant' is a measure of is a measure of the strength of an acid or a base under certain pH. the strength of an acid or a base under certain pH. Strong acids and bases Strong acids and bases - defined as completely ionized in pH range defined as completely ionized in pH range 0-14 Weak acids and bases Weak acids and bases - defined as incompletely ionized in pH range defined as incompletely ionized in pH range 0-14 2. Significance: 2. Significance: pKa pKa solubility absorption solubility absorption
1.2.pH and pKa 3.calculation: The Henderson-Hasselbalch equation: Weak acids:AHA+H+Ka=[A-][H+]/[AH] Weak bases:BHt←→B+HtKa=[B]H]/BHt] For acidic compounds: pH pKa log ([ionized drug]/[un-ionized drug]) For basic compounds: pH pKa log ([un-ionized drug]/[ionized drug]) pH pKa a substance is 50%ionized pH pKa 2, a substance is 99%at neutral form pH pKa 2, a substance is 99%ionized
1.2. pH 1.2. pH and pKa 3. calculation: 3. calculation: The Henderson The Henderson-Hasselbalch Hasselbalch equation: equation: Weak acids: AH Weak acids: AH ↔ A- + H+ Ka= [A-][H+]/[AH] Weak bases: BH Weak bases: BH+ ↔ B + H+ Ka= [B][H Ka= [B][H+]/[BH+] For acidic compounds: For acidic compounds: pH = pKa + log ([ionized drug]/[un + log ([ionized drug]/[un-ionized drug]) ionized drug]) For basic compounds: For basic compounds: pH = pKa + log ([un + log ([un-ionized drug]/[ionized drug]) ionized drug]/[ionized drug]) pH = pKa a substance is 50% ionized a substance is 50% ionized pH = pKa – 2, a substance is 99% at neutral form 2, a substance is 99% at neutral form pH = pKa + 2, a substance is 99% ionized + 2, a substance is 99% ionized