The absorption of drugs through the GIT is affected by multiple factors, which can be broadly classified into the following categories:

Physicochemical Properties of the Drug
The inherent chemical and physical properties of a drug significantly influence its absorption.
A) Solubility
A drug must be in solution to be absorbed. Poorly soluble drugs may have limited absorption.
B) Particle Size
Smaller particles dissolve faster and are absorbed more readily than larger ones.
C) Ionization and pH–Partition Hypothesis
The extent of drug ionization (determined by its pKa and the pH of the GIT) affects absorption. Non-ionized (lipid-soluble) forms diffuse across membranes more efficiently.
D) Lipophilicity
Lipid-soluble drugs cross biological membranes more easily via passive diffusion.
Formulation and Dosage Form Factors
The design and composition of the drug product can impact its dissolution and absorption.
A) Disintegration and Dissolution
Tablets/capsules must disintegrate and dissolve before absorption can occur.
B) Excipients and Additives
Certain ingredients like binders, fillers, and surfactants can enhance or hinder dissolution and absorption.
C) Coatings
Enteric coatings protect drugs from gastric acid, delaying absorption until reaching the intestine.
Modified-release formulations (e.g., sustained-release tablets) can alter the rate and extent of absorption.
Anatomical and Physiological Factors
Various structural and functional characteristics of the GIT impact drug absorption.
A) Surface Area
The small intestine (duodenum) has a large surface area (due to villi and microvilli), which enhances absorption.
B) Blood Flow to GIT
Higher blood perfusion increases drug uptake and transport into systemic circulation.
C) Gastric Emptying and Intestinal Transit Time
Delayed gastric emptying (e.g., due to food or certain drugs) can slow the rate of absorption.
Rapid intestinal transit may reduce absorption if the drug has limited time for dissolution and membrane permeation.
The stomach is acidic (pH ~1-3), favoring absorption of weak acids.
The small intestine is alkaline (pH ~5-7), favoring absorption of weak bases.
E) Presence of Food
Food can delay gastric emptying and alter GIT pH.
Certain foods interact with drugs, e.g., calcium (Ca²⁺) and iron (Fe³⁺) binding to some drugs, reducing absorption.
Biological and Pathological Conditions
Factors related to the patient’s biological state or disease conditions can also impact drug absorption.
A) Age
Neonates and elderly patients may have altered gastric pH, enzyme activity, and GI motility, affecting absorption.
B) Diseases
Conditions such as Crohn’s disease, celiac disease, or gastric bypass surgery can reduce the absorption surface area or alter drug transport mechanisms.
C) Drug Interactions
Some drugs alter gastric pH (e.g., proton pump inhibitors reducing acid production).
Others affect gastric motility (e.g., anticholinergics slowing gastric emptying).