**6. Factors affecting absorption of drugs**

#### **6.1. Surface area**

For any substance that can penetrate the GIT in measurable amounts, the small intestine represents the greatest area of absorption. For instance, ethanol can be absorbed by the stomach, but it is absorbed eight times faster from the small intestine because of the large surface area provided by the villi. The rate at which the stomach empties its contents into the small intestine also markedly affects the overall rate at which drugs reach general circulation after oral administration. For this reason many agents are administered on an empty stomach with sufficient water to ensure their rapid passage to the small intestine.

#### **6.2. Tissue pH**

Drugs can be classified either as organic amines or organic acids and therefore their absorption is markedly affected by pH. Tertiary amines are not charged at high pH and have a high lipid/ water partition coefficient and hence readily penetrate membranes.

At low pH, the tertiary amine is protonated and has low lipid/water partition coefficient thus lower rate of permeation.


In case of an organic acid, the same general principle applies. The unprotonated organic acid at low pH permeates the tissues more readily as compared to the charged form of the drug at high pH.

Low pH High pH R-COOH ⇌ R – COO- + H<sup>+</sup> Stomach Intestine Therefore organic acids such as barbiturates and acetyl salicylic acid (aspirin) have a higher absorption rate in the stomach.

The degree of ionization of the drug when in the GIT or other body fluids is the main deter‐ minant of the amount of the drug found in an uncharged form and this depends upon the relation between pH of the fluid and the pKa of the drug:

Acidic drugs:

**5.4. Pinocytosis and phagocytosis of drugs**

**6. Factors affecting absorption of drugs**

somal system.

480 Drug Discovery

**6.1. Surface area**

**6.2. Tissue pH**

N R R

R H

Stomach Low pH

at high pH.

lower rate of permeation.

(protonated form) Lower absorption

Low pH High pH R-COOH ⇌ R – COO-

Stomach Intestine

Proteins, bacterial toxins and drugs with high molecular weights, (1000 KDa or more) en‐ ter cells by means of pinocytosis and endocytosis. These substances finally enter the lyso‐

For any substance that can penetrate the GIT in measurable amounts, the small intestine represents the greatest area of absorption. For instance, ethanol can be absorbed by the stomach, but it is absorbed eight times faster from the small intestine because of the large surface area provided by the villi. The rate at which the stomach empties its contents into the small intestine also markedly affects the overall rate at which drugs reach general circulation after oral administration. For this reason many agents are administered on an empty stomach

Drugs can be classified either as organic amines or organic acids and therefore their absorption is markedly affected by pH. Tertiary amines are not charged at high pH and have a high lipid/

At low pH, the tertiary amine is protonated and has low lipid/water partition coefficient thus

In case of an organic acid, the same general principle applies. The unprotonated organic acid at low pH permeates the tissues more readily as compared to the charged form of the drug

R

R

R

+ H+

(unprotonated form) Higher absorption.

Small intestines

High pH

with sufficient water to ensure their rapid passage to the small intestine.

water partition coefficient and hence readily penetrate membranes.

+ N

+ H<sup>+</sup>

RCOOH⇌ Ka RCOO- + H<sup>+</sup>

Basic drugs:

R –<sup>+</sup> NH3⇌ Ka RNH2+ H<sup>+</sup>

If the pH of the fluid is low, the ionization of acidic drugs is less while the ionization of basic drugs will be high.When the pKa of a drug is equal to the pH of the surrounding fluid, there is 50% ionization.
