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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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