factors affecting drug absorption
TRANSCRIPT
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FACTORS AFFECTING DRUG ABSORPTION
Name: Deepak.S.PandeyM.Pharm (Ist year)
Advanced Pharmaceutics.Parul university
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LIST OF CONTENTS:• INTRODUCTION OF ABSORPTION• TRANSPORT PROCESS• FACTORS AFFECTING DRUG ABSORPTION: 1)Physiological factors 2)physiochemical factors 3)pharmaceutical factors• REFERENCES
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ABSORPTION:• Definition: The process of movement of
unchanged drug from the site of administration to systemic circulation.
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CELL MEMBRANE:• Cell membrane mainly consists of: 1) Lipid bilayer:- -phospholipid -Cholesterol -Glycolipids 2) Proteins:- -Integral membrane proteins -Lipid anchored proteins -Peripheral Proteins
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TRANSPORT PROCESS:
• PASSIVE DIFFUSION• PORE TRANSPORT• FACILITATED DIFFUSION• ACTIVE TRANSPORT• PINOCYTOSIS
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1.PHYSIOLOGICAL FACTORS:
• AGE• GASTRIC EMPTYING• INTESTINAL TRANSIT• GASTRO INTESTINAL PH• DISEASE STATE• GASTRO INTESTINAL CONTENTS• PRESYSTEMIC METABOLISM.
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AGE:
• In children & Infants Gastric pH is high and intestinal surface and flow to git is low.
• while in adults altered gastric emptying, decrease intestinal surface area, decrease gastric blood flow & higher incidence of achlorhydria cause impaired drug absorption.
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Gastric emptying:
• Gastric emptying is the passage of drug from stomach to small intestine.
• Gastric emptying is delayed when co-administered with food.
• Factors that influence G.E are :volume of meal, composition of meal, physical state and viscosity of meal, temperature of meal, body posture, exercise ,disease state etc.
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Intestinal transit time:
• Since, intestine is the major site of absorption of most of the drugs, Long intestinal transit time is desirable for the complete absorption of drugs.
• Delayed intestinal transit is desirable for : --Drugs that dissolve only in intestine (enteric coated ). --Drugs absorbed from specific sites in the intestine.
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Gastro intestinal PH:
• A difference in PH is observed between gastric and colon fluids. The GI PH increases gradually from stomach to the colon and rectum.
• The PH of GI fluids influence the drug absorption in several ways:
-dissolution -stability.
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DISEASE STATE:
• GI Disease: Infection such as Achlorhydria, malabsorption and surgeries such as gastrectomy affect the absorption of drugs to a greater extent.
• Disorders such as hepatic cirrhosis influence bio-availability mainly of drugs that undergo considerable first-pass hepatic metabolism e.g. Propranolol
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Presystemic metabolism:
The main reason for the decrease in bioavailability of a drug are decreased absorbtion or first pass metabolism. various enzyme that affect presystemic meatbolism of drugs are : -gutwall enzyme -hepatic enzyme -bacterial enzyme.
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2)Physicochemical factors:
• DRUG SOLUBILITY & DISSOLUTION RATE.• PARTICLE SIZE• POLYMORPHISM &AMORPHISM• PSEUDOPOLYMORPHISM• SALT FORM OF THE DRUG• Pka OF THE DRUG
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Particle size:
The absorption of the drug can be increased by increasing the particle surface area by micronization.
Smaller the drug particle
Greater the surface area
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Polymorphism and amorphism:
• When substance exists in different crystallineforms it is polymorphism.
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AMORPHISM:
• They have greater aqueous solubility than the crystalline forms because the energy required to transfer a molecule from crystal lattice is greater than that required for the non crystalline solid.
• Eg:Novobiocin• The order of Dissolution & hence Absorption for
different solid dosage forms is amorphous > meta-stable > stable.
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PH PARTITION HYPOTHESIS:
UNIONISED DRUG HIGH ABSORPTION
IONISED DRUG LOW ABSORPTION
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SALT FORMATION OF A DRUG:
• Salt of weak acid and weak bases have much higher aqueous solubility than the free acid or base.• Therefore, if the drug can be given as a salt, the solubility can be increased & the dissolution can be improved.
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3)Pharmaceutical factors:
• MANUFACTURING VARIABLES: -Method of granulation -Compression force.• NATURE AND TYPE OF DOSAGE FORM.• PHARMACEUTICAL INGREDIENT AND
EXCIPIENTS.• STORAGE CONDITIONS.
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Manufacturing variables:
1) Method of granulation: The method of dry granulation can be used to produce tablets that dissolve at a faster rate. 2) compression force: Influence the hardness, density,porosity,disintegration,dissolution of tablet.
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Nature and type of dosage form:
• Bioavaibility of a drug from various dosage form is in the following order:
• solution>emulsion>suspension>Capsules>tablets>coated tablets>enteric coated tablet>sustained release tablet
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• Pharmaceutical excipients.
• Product storage condition.
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REFERENCE:
• TEXTBOOK OF BIOPHARMACEUTICS AND PHARMACOKINETICS,BY D.M.BRAHMANKAR And SUNIL .B. JAISWAL,
PG.NO.5-97.
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•Thank you.