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Factors Influencing
Absorption
pH Partition Hypothesis
(Drug pka, Lipophilicity, GI pH & Limitations)
Name: Arya B. Bidikar
Roll No.: 05
Class: [Link], Sem 6th
Subject: Biopharmaceutics &
Pharmacokinetics
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Department: Pharmaceutics
Click to edit Master
pH title style hypothesis
partition
• According to Brodie [Link], drug compounds with a molecular weight greater than 100 are
primarily transported across the biomembrane through passive diffusion.
• The process of absorption is governed by,
I. Dissociation constant (pKa) of the drug
II. Lipid solubility of the unionised drug (Ko/w)- lipophilicity
III. The pH at the absorption site
• Drug – weak acid or base degree of ionisation depends on the pH of biological fluid.
• Drugs permeate passively through the membrane if
o Drug undissociated or unionised
o Sufficiently lipid soluble
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• Click tostatement
The above edit Master title
of the hypothesis wasstyle
based on the assumption that:
i. The GIT is a simple lipoidal barrier to the transport of drugs.
ii. Larger fraction of unionised drugs faster the absorption.
iii. Greater the lipophilicity (Ko/w) of the unionised drug better the absorption.
1. Drug pKa and GI pH
• The amount of unionised drugs is a function of the drug dissociation constant
(pKa) and the pH of the fluid.
o Lower pKa of acidic drug stronger acid (more ionisation)
o Higher pKa of basic drug stronger base (more ionisation)
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Henderson-Hasselbalch
Click equation
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Determine the amount of drug that exists in unionised form is a function of the
dissociation constant (pKa) of the drug and pH of the drug and pH of the fluid at the
absorption site.
For weak acids:
pH = pKa + log (Ionised drug) %Drug Ionised = 10(pH-pKa)
* 100
(Unionised drug) 1+10 (pH - pKa)
For weak bases:
pH = pKa + log (Unionised drug) %Drug Ionised = 10(𝑝𝐾𝑎−𝑝𝐻) * 100
(Ionisied drug ) 1 + 10(𝑝𝐾𝑎 −𝑝𝐻)
❖ If concentration of the unionised drug and ionised drug become equal
(log1= zero)
pH = pKa (pKa is the characteristic of drug) 4 4
2. Lipophilicity/ Partition
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(𝒌𝒐/𝒘)title style
❑ Biological members are usually lipoidal in nature therefore, the lipid solubility of the drug is a
major parameter for its absorption.
❑ Example – Opium alkaloids like morphine, thebaine and codeine (contain two, zero and one
hydroxyl groups, respectively).
• It is reported that the absorption rate decreased by enhancing the polarity of
molecules.
❑ Perfect hydrophilic-lipophilic balance (HLB) should be there in the structure of the drug for
optimum bioavailability
❑ Lipophilicity of unionised fraction will determine its permeability.
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❑ For optimum absorption, the drug should have
• Aqueous solubility to dissolve (Hydrophilicity)
• solubility ( log P or 𝐾𝑜/𝑤 ) for permeation (Lipophilicity)
❑ It is determined from its oil/water partition coefficient.
❑ It is a measure of the degree of distribution of a drug between several organic solvents and
an aqueous solvent.
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Limitations title
of the pH style
– partition
hypothesis
1. Presence of virtual membrane pH
2. Absorption of unionised drug
3. Influence of GI surface area and residence
time of drug
4. Presence of aqueous unstirred diffusion layer
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[Link]
Presence
to editof a virtual
Master titlemembrane
style
▪ pH- partition hypothesis – only unionised
drug absorbed at GI lumen pH
▪ An S-shaped curve, called a pH-absorption
curve
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▪ The experimental pH-absorption curves are less steep,
• Shift to the left (lower pH values) for a basic drug
• Shift to the right (higher pH values) for an acidic drug
▪ This led to suggestions that a virtual pH, also called the microclimate
pH
▪ Microclimate pH different from the liminal pH exists at the membrane
surface
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2. Absorption
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of ionised
title drugs
style
▪ Assumption – the unionised drug is absorbed and permeation
of the ionised drug is negligible.
▪ The experimental pH-absorption curves are shift-suggested
• Ionised drugs absorb to a considerable extent (more
lipophilic).
• Other mechanisms involve – active transport, ion-pair
and convective flow.
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3. Influence of GI surface area
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andtoresidence
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time of style
drug
▪ According to the pH-partition theory-
• Acidic drugs (unionised) are best absorbed from the stomach
(acidic pH)
• Basic drugs (unionised) are best absorbed from the intestine
(alkaline pH)
▪ But both acidic and basic drugs are more rapidly absorbed from the
intestine because of
• Its large surface area
• Resident time of the drug in the intestine
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4. Presence of aqueous
Clickunstirred
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diffusion style
▪ The bulk of the luminal fluid is not in
direct contact with the membrane but a
barrier called aqueous unstirred diffusion
layer between them.
▪ Drug must diffuse first through the
aqueous barrier and then the lipoidal
barrier.
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▪ Despite its limitations, the pH-partition theory is still useful in the basic
understanding of drug absorption and the movement of drugs between
various body compartments.
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Thank-You
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