Drug absorption refers to the movement of an unchanged drug from the site of administration into systemic circulation. It is affected by pharmaceutical, formulation, physiological, and patient-related factors. Pharmaceutical factors include a drug's solubility, particle size, polymorphism, salt form, and ionization state which impact dissolution rate and permeability. Formulation factors like disintegration time, excipients, and dosage form properties also influence absorption. Physiological factors such as gastrointestinal motility, pH, enzyme activity, blood flow, and food intake can impact drug stability and transit time in the GI tract. Patient characteristics such as age, disease state, and genetics additionally determine absorption. Together, these multifaceted factors determine the degree and rate of drug

1. PREPARED BY: KOLAPKAR JYOTI
M. PHARMA (PHARMACEUTICS) 1ST. YEAR

2. The process of movement of unchanged drug from
the site of administration to the systemic
circulation
DEFINITION OF DRUG ABSORPTION
BIOAVAILABILITY
Bioavailability is the degree and rate at
which a drug is absorbed by the body.
FIRST-PASS METABOLISM
First-pass metabolism refers to
the breakdown of drugs in the
liver before they reach the
systemic circulation. It affects
drug bioavailability.

4. FACTORS AFFECTING DRUG ABSORPTION
1) PHARMACEUTICAL FACTORS
A] Physicochemical properties of drug substances
1. drug solubility & dissolution rate
2. Particle size & effective surface area
3. Polymorphism & amorphism
4. Solvates & hydrates
5.salt form of drug
6. ionization state
7.Drug pKa & lipophilicity & Gl pH-pH partition hypothesis.

5. 1. Drug solubility & dissolution rate: The dissolution rate affects drug bioavailability, onset time, and efficacy.
For Hydrophobic drugs
Dissolution is rate limited step. e.g. Griseofulvin, spironolactone.
For Hydrophilic drugs,
permeation is rate limited step. e.g. cromolyn sodium, neomycin.
2. Particle size & effective surface area: As particle size decreases, the effective surface area increases, leading to
higher reactivity and increased surface energy. This impacts properties like solubility, melting point, and reaction
rate.
3. Polymorphism & amorphism
Crystalline drugs have a defined structure and dissolve consistently, while amorphous drugs lack structure,
dissolve quickly, and are less stable.
E.g., Novobiocin
Amorphous form → More soluble, → Rapidly dissolving, →Readily absorbed
Crystalline form →Less soluble, →Slower dissolving, →Not absorbed to a significant extent

6. 4. Solvates & hydrates
Solvates form when a solvent molecule becomes trapped within a crystal lattice.
Hydrates form when water molecules become trapped within a crystal lattice.
Solvates have higher solubility, while hydrates have lower solubility due to water molecules bound to
the drug.
5. Salt form of the drug
Salt formation approaches have widely been utilized to increase solubility, and therefore, the dissolution
rate of a drug. It is one of the most common methods to increase the solubility of weakly acidic and basic
drugs
6. ionization state
Most drug absorption is by passive diffusion, thus absorption from the gastrointestinal tract is favored
when a drug is in its unionized, more lipophilic form.

7. 7.Drug pKa & lipophilicity & Gl pH-pH partition hypothesis.
pKa is the pH at which a drug is 50% ionized and 50% non-ionized.
The pH-Partition Hypothesis explains how drug absorption is influenced by the pH of the
gastrointestinal tract. The lipophilic drugs that are non-ionized get absorbed faster. Ionized
hydrophilic drugs take longer. Understanding this process is crucial for drug design and delivery.
Examples of Drugs with Varied Properties
Aspirin: low pKa and lipophilicity, high solubility in an acidic environment.
Diazepam: high lipophilicity, low solubility in Gl environment.
Metoprolol: high pKa, low lipophilicity, highly soluble in Gl environment.
A drug's lipophilicity determines its absorption, distribution, and elimination. The higher the
lipophilicity, the higher the cell membrane permeability.

8. FACTORS AFFECTING DRUG ABSORPTION
B] Formulation Factors
1. Disintegration time
2. Manufacturing variables
3. Pharmaceutical ingredients
4. Nature & type of dosage form
5. Product age & storage conditions

9. 1. Disintegration time
Rapid disintegration is important to have a rapid absorption so lower D.T. is required.
D.T of a tablet is directly proportional to Amount of binder and Compression force.
2. Manufacturing variables
• Method of granulation
• compression force
3. Pharmaceutical ingredients
More the no. of excipients in dosage form, the more complex it is & greater the potential for
absorption and Bioavailability problems. EG., Changing an excipient from calcium sulfate to
lactose and increasing the proportion of magnesium silicate, increases the activity of oral
phenytoin.

10. 3. Nature & type of dosage form

11. 5. Product age & storage conditions
-Product aging and improper storage conditions adversely affect B.A.
-E.g.- precipitation of a drug in a solution decrease the rate of Change in
the particle size of suspension drug dissolution
& Hardening of tablet & absorption..

12. [A] PHYSIOLOGICAL FACTORS
(1) Membrane physiology
A. Nature of cell membrane
B. Transport processes
(2)Gastro-Intestinal motility
A. Age
B. Gastric emptying rate
C. Intestinal motility
D. Drug stability in GIT
E. pH of GIT
F. Surface area of GIT
G. Intestinal transit
H. Blood flow to GIT.
I. Effect of food
PATIENT RELATED FACTORS

13. A. Age
In infants, the gastric pH is high, and intestinal surface and blood flow to the GIT is low
resulting in an altered absorption pattern in comparison to adults. In elderly persons, causes of
impaired drug absorption include altered gastric emptying, decreased intestinal surface area and GI
blood flow, higher incidents of achlorhydria, and bacterial overgrowth in the small intestine.
B. Gastric emptying rate
increasing the rate of gastric emptying and gastrointestinal motility increases the rate of absorption
of a drug but, for digoxin and riboflavin, increased gastrointestinal motility is associated with a
decrease in the rate of absorption.
C. Intestinal motility
In the case of high motility in the intestinal tract, as in diarrhea, the drug has a very brief residence
time and less opportunity for adequate absorption.
D. Drug stability in GIT
Metabolism or degradation by enzymes or chemical hydrolysis may adversely affect the drug
absorption and thus reduces B.A. Destruction in gastric acid.

14. E. pH of GIT
-Acidic drugs ( Aspirin) are more absorbed in the stomach (in acidic media)
-Basic drugs( Diazepam) are better absorbed in the intestine ( in alkaline media)
F. Surface area of GIT
Drug absorption is enhanced if there is a large surface area available for absorption (e.g. villi/microvilli
of the intestinal tract)
G. Intestinal transit
The major site of absorption of most of drugs, peristaltic contractions promote drug absorption,
Delayed intestinal transit is desirable for sustain release products, Enteric-coated formulations, several
B vitamins
H. Blood flow to GIT
Lipid soluble molecules highly depend on the blood flow, Food influences flow to the GIT. , maintain the
concentration gradient across the epithelial membrane
I. Effect of food
The absorption of some antibiotics, such as penicillin and tetracycline, is decreased with food; whereas
other drugs, particularly lipid-soluble drugs such as griseofulvin and metaxalone, are better absorbed
when given with food containing a high fat content.

15. Reference:
TEXTBOOK OF BIOPHARMACEUTICS AND PHARMACOKINETICS, BY D.M.BRAHMANKAR And SUNIL.B.
JAISWAL,
PG.NO.5-97.
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