Drug absorption & its influenci

ng factors

-BY APUSI CHOWDHURY 23rd BATCH

ContentDrug absorptionInfluencing factorsPhysiological factorsPhysicochemical nature of

drugPharmaceutical factorsEffect of disease states on

drug absorptionGI content affecting

absorptionDrug-food interaction

affecting absorptionDrug-drug interaction

affecting absorptionEffect of excipientsReferences

Drug absorption

The process of movement of unchanged drug from the site of administration to systemic circulation.

Drug absorpti

on influenci

ng factors

Physiological factors

Pharmaceutical factors

Physicochemical factors

Drug absorption factors

Physiological factors

• Route of administration

• Membrane physiology– Nature of cell

membrane– Transport process

• Age• Gastric emptying

time• Intestinal transit

time• Gastrointestinal pH • Disease states • Blood flow through

the GIT

• Gastrointestinal contents:– Food- drug

interactions – Fluids – Other normal GI

contents • Pre-systemic

metabolism by: – Luminal enzymes – Gut wall enzymes – Bacterial enzymes – Hepatic enzymes

Physicochemical factors

Drug solubility & dissolution rate

Particle size & effective surface area

Polymorphism & amorphism

Pseudopolymorphism (hydrates/solvates)

Salt form of the drug

Lipophilicity of the drug (pH- Partition-hypothesis)

pKa of drug & gastrointestinal pH

Drug stability

Pharmaceutical factors

1) Disintegration time (tablets/capsules)

2) Dissolution time3) Manufacturing variables4)Pharmaceutical ingredients

(excipients/adjuvants)5) Nature & type of dosage form6) Product age & storage condition

Effects of disease

states on drug

absorption

s1Drug absorption may be affected by any disease that causes changes in the:

Intestinal blood flow Gastro intestinal motility Stomach emptying time Gastric pH that affects drug

solubility Intestinal pH that affect

ionization Gut wall permeability Bile secretion Digestive enzyme secretion Alteration of GI flora

Gastrointestinal contents

affecting absorption

Altered absorption

Interaction between drug &

normal GI contents

Food -drug

interaction

Drug -drug

interaction

Drug-food interaction

Absorption of water soluble vitamins, such as vitamin B-12 & folic acid, are aided by special absorption mechanism.Grapefruit juice often increases

bioavailability, as observed by an increase in plasma levels of many drug that are substrates for cytochrome p-450 (CYP) 3A4.  In general presence of food either delay,

reduce, increase or may not affect absorption.

Aspirin Delayed Penicillin DecreasedGriseofulvin Increased Methyldopa Unaffected 

DRUG-DRUG INTERACTION AFFECTING

ABSORPTION

Propanthelin Digoxcin

Antacid Cimetidine

Cholestryamine

Warfarin

absorptio

nab

sorptio

nab

sorptio

n

Interaction of drug

with GI conten

t

• GIT contains no. of normal constituents such as mucin, bile salts and enzymes, which influence the drug absorption.

E.g. Bile salts

Increase absorption of Vitamins (Solution)Decrease absorption of Neomycin and Kanamycin (Insoluble complex) .

Intrinsic factor enhances vit B-12 absorption.

Effect of excipients

Excipients

Example Ka Tmax AUC

Disintegrants

Avicel, Explotab

Lubricants

Talc, Hydrogenated vegetable oil

Coating agent

Hydroxypropylmethyl cellulose

Enteric coating

Cellulose acetate phthalate

Sustained release agents (waxy agents)

Castorwax, carbowax

Sustained release agents (gum/viscous)

Veegum, keltrol

REFERENCES1. Brahmankar D.M., Jaiswal S.B., First edition, “Absorption of Drugs” Biopharmaceutics and Pharmacokinetics – A treatise, Vallabh Prakashan, Delhi 1995.2. Shargel L., Andrew B.C., Fourth edition “Physiologic factors related to drug absorption” Applied Biopharmaceutics and Pharmacokinetics, Prentice Hall International, INC., Stanford 1999.3. Aulton M.E. Pharmacetutics “The Science of Dosage Form Design”, 2nd Ed.; Churchill Livingstone.

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