Physiological factors affecting

drug absorption
By Eesha Tariq Bhatty
Mphil, Pharm D., R.Ph.
• Drugs administered orally pass through various parts of the enteral
canal, including the oral cavity, esophagus, and various parts of the
gastrointestinal tract
• Residues eventually exit the body
• The total transit time, including gastric emptying, small intestinal
transit, and colonic transit, ranges from 0.4 to 5 days
• The most important site for drug absorption is the small intestine.
• Small intestine transit time (SITT) ranges from 3 to 4 hours for most
healthy subjects
• If absorption is not completed by the time a drug leaves the small
intestine, absorption may be erratic or incomplete
• The small intestine is normally filled with digestive juices and liquids,
keeping the lumen contents fluid
• In contrast, the fluid in the colon is reabsorbed, and the lumenal
content in the colon is either semisolid or solid, making further drug
dissolution erratic and difficult
• The lack of the solubilizing effect of the chyme and digestive fluid
contributes to a less favorable environment for drug absorption in the
colon
Oral drug absorption
• Oral Cavity
• Esophagus
• Stomach
• Small intestine
• Duodenum
• Jejunum
• Ileum
• Colon
• Rectum
Oral cavity
• Saliva is the main secretion (1500 mL/day)
• Saliva contains amylases
• The pH is 6-7
• Highly vascular area
Esophagus
• pH of 5-6
• No drug absorption from this site
• Very little dissolution
• Stomach :
• The surface area for absorption of drugs is relatively small in the stomach
due to the absence of macrovilli & microvilli.
• Extent of drug absorption is affected by variation in the time it takes the
stomach to empty, i.e., how long the dosage form is able to reside in
stomach.
• Drugs which are acid labile must not be in contact with the acidic
environment of the stomach.
• pH of 1.5 -2 (fed-state) or 2 – 6 (fasted-state).
• HCl secretion of the stomach is stimulated by gastrin and histamine
(hormones).
• High-density foods generally are emptied from stomach more slowly.
Small Intestine
• Include duodenum, jejunum and ileum.
• Major site for absorption of most drugs due to its large surface area.
• The Folds in small intestine called as folds of kerckring, result in 3 fold
increase in surface area.
• These folds possess finger like projections called Villi which increase the
surface area 30 times.
• From the surface of villi protrude several microvilli which increase the
surface area 600 times.
• Blood flow is 6-10 times that of stomach.
• pH Range is 6–7.5 , favorable for most drugs to remain unionised.
• Peristaltic movement is slow, while transit time is long.
• Permeability is high.
• The drugs which are predominantly absorbed through the small
intestine, the transit time of a dosage form is the major determinant
of extent of absorption.
• The transit time in small intestine for most healthy adults is between
3 to 4 hours, and a drug may take about 4 to 8 hours to pass through
the stomach & small intestine during fasting state.
• During the fed state, the small intestine transit time may take about 8
to 12 hours.
Large intestine
• Include colon and rectum
• Lack villi
• Limited absorption from colon
• The major function of large intestine is to absorb water from ingestible
food residues which are delivered to the large intestine in a fluid state, &
eliminate them from the body as semi solid feces.
• pH ranging from 5.5-7
• Colon contains microorganisms
• Only a few drugs are absorbed in this region.
Influence of drug pKa and GI pH on drug
absorption
Drugs
Very weak acids (pKa > 8.0)
Moderately weak acids (pKa 2.5 – 7.5)
Strong acids (pKa <2.5)
Very weak bases (pKa < 5)
Moderately weak bases (pKa 5 – 11 )
Strong bases (pKa >11)
Site of absorption
Unionized at all pH values
Absorbed along entire length of GIT
Ionionized in gastric pH
Ionized in intestinal pH
Better absorbed from stomach
Ionized at all pH values
Poorly absorbed from GIT
Unionized at all pH values
Absorbed along entire length of GIT
Ionized in gastric pH
Unionized in intestinal pH
Better absorbed from intestine
Ionized at all pH values
Poorly Absorbed from GIT
GIT motility and Gastric Emptying

• GI motility tends to move the drug through the alimentary canal.

• For each drug there is an optimal absorption window.
• Physiologic movement of drug within the GIT depends on fed/fasted
state.
• The time a dosage form takes to leave the stomach is usually termed:
the gastric residence time, gastric emptying time.
Rapid Gastric Emptying Advisable when :

• Rapid onset of action is desired eg. Sedatives

• Dissolution occurs in the intestine eg. Enteric coated tablets
• Drugs not stable in GI fluids eg. penicillin G
• Drug is best absorbed from small intestine eg. Vitamin B12
Delay in Gastric Emptying recommended when

• Food promotes drug dissolution and absorption e.g. Gresiofulvin

• Disintegration and dissolution is promoted by gastric fluids
Factors affecting Gastric Emptying
Volume of Ingested Material Bulky material tends to empty more slowly than liquids
Type of Meal Gastric emptying rate:
carbohydrates > proteins > fats
Temperature of Food Increase in temperature, increase in emptying rate
Body Position Lying on the left side decreases emptying rate and right side promotes it
GIT pH Retarded at low stomach pH and promoted at higher alkaline pH
Emotional state Anxiety and stress promotes where as depression retards it
Disease states gastric ulcer, diabetes and hypothyroidism retards it, while duodenal ulcer,
hyperthyroidism promotes it.
Effect of Food
• The presence of food in the GIT can influence the rate and extent of
absorption, either directly or indirectly via a range of mechanisms.
• As a general rule, drugs are better absorbed under fasting conditions.
• Presence of food may retard or prevent drug absorption.
• Generally the extent of absorption is not greatly reduced.
• Occasionally absorption may be improved
• Food does not significantly influence absorption of a drug taken half
an hour or more before meals and two hours or more after meals.
• Increased drug absorption following a meal can be due to the
following reasons
• Increased time for dissolution of poorly soluble drug
• Enhanced solubility due to GI secretions like bile
• Prolonged residence time and absorption site contact of the drug e.g.
water-soluble vitamins.
• Delayed or decrease drug absorption by food can be due to one or more of
the following reasons:
• Delayed gastric emptying, affecting the drugs unstable in the stomach e.g.
penicillin, erythromycin.
• Preventing the transit of enteric tablets into the intestine which may be as
long as 6 – 8 hrs.
• Formation of poorly soluble, unabsorbable complex e.g. tetracycline-
calcium complex.
• Alteration of pH
• Competition between food components and drugs for specialized
absorption mechanisms
Types of meal

a) Meals high in fat aid solubilisation of poorly aqueous soluble drugs

like griseofulvin.
b) Food high in proteins increases oral availability of propranolol
because
• such a meal promotes blood flow to the GIT helping in drug absorption.
• increases hepatic blood flow due to which the drug can bypass first-pass
hepatic metabolism (propranolol is a drug with high hepatic metabolism)