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Biological Factors Affecting Absorption

Presented By Ishita Bajpai Ist Mpharm Department Of Pharmaceutics Al Ameen College Of Pharmacy

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Absorption Absorption is the transfer of a drug from its site of

administration to the bloodstream. The rate and efficiency of absorption depend on the route

of administration. For IV delivery, absorption is complete=100 %

bioavailability; That Is, The Total Dose Of Drug Reaches The Systemic

Circulation

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Absorption

The primary stage involves food ingestion•It starts from the oral level , thereby food enters the alimentary tract , later it is absorbed at• 1. liver (Ist pass )•2 stomach•3 small intestine(proteins )•4 large intestine•5 unabsorbed food passes through rectum, anal opening

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Biological Factors Affecting Absorption

Contents

Definitions Factors Summary Bibliography/reference

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Factors Affecting Absorption

Classified As A) Biological / Intrinsic Factors = pertaining to living systemB) Pharmaceutical /Extrinsic Factors =pertaining to drug

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Biological factors are

10 . Gastric emptyingFactors affecting :-

i.Presence of foodii.Nature of food i.e.

lipids/proteiniii.Viscosity of mealiv.Volume of mealv.Time of mealvi.Presence of herbsvii.Presence of

chelating agents /other drugsviii.Git disorders like

ulcer etcix.Emotional factors/

psychological influence

1.Local ph of gut2.Contact time at the

absorption surface /transit time 3.Surface area of gut4.Blood flow to gut5.First pass metabolism6.Route of administration7.Patient age.8.Motility of intestine9.Motility of

gut/gastrointestinal tract

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Effect of ph on drug absorption

The pH increases gradually from mouth to colon and it influences drug absorption in several ways. Disintegration of some dosage forms depends upon pH.

Ex: Enteric coating formulations disintegrate in the intestine and release their drugs in the intestine. They do not disintegrate in the stomach.

Weakly acidic drugs dissolve rapidly in the alkaline pH of the intestine. Whereas basic drugs dissolve rapidly in acidic pH of the stomach. Since absorption follows dissolution, and dissolution depends on pH, we can say that pH influences absorption.

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Contact Time At The Absorption Surface

If a drug moves through the GI tract very quickly, as in severe diarrhea, it is not well absorbed.

Conversely, anything that delays the transport of the drug from the stomach to the intestine delays the rate of absorption of the drug.

Absorption can be limited by the short transit period of the drug through the small intestine (2-4 hours).

Transit time

Time during which the drug is in proximity of the absorbing gastrointestinal surface i.e. from the stomach to the end of small intestine is approximately 12 hours

Due to more favorable absorbing conditions in upper intestine most drugs absorbed better in upper intestine than in lower intestine

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Total Surface area of gut

Surface area available for absorption: Because the intestine has a surface rich in microvilli, it has a surface area about 1000-fold that of the stomach; thus, absorption of the drug across the intestine is more efficient.

Colon is usually a poor site of absorption due to its low permeability and relatively low surface area

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Blood flow to gut /absorption site

Blood flow to the intestine is much greater than the flow to the stomach; thus, absorption from the intestine is favored over that from the stomach.Drugs administered intramuscularly or subcutaneously are completely absorbed unless destruction occurs at the site of administration or during first-pass (e.g. for macromolecules such as vaccines). Absorption from these sites is highly dependant on the blood flow at the site of injection.

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First-pass hepatic metabolism

When drug absorbed across GIT, it enters portal circulation before entering systemic circulation.

If the drug is rapidly metabolized by the liver, the amount of unchanged drug that reaches systemic circulation is decreased.

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First pass metabolism

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Route of administration

Route of administration Oral i.e. enteral =slow absorption

due to number of steps Per oral/parenteral (injections)=

faster as total quantity of drug enters systemic circulation

Nasal=good and timely absorption Topical= absorption is gradual and

systematic

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Route Of Administration: An Illustration

Drugs inhaled orally directly reach lungs .Fewer steps of metabolism/ biotransformation

Drugs swallowed orally maybe inactivated by liver and then enter systemic circulationThus, more steps of metabolism/ biotransformation .Lesser extent of drug absorbed in systemic circulation.

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Patient age and sex

Infants , neonates : slow absorption of drug due to immature body organs and underdevelopment of tissues , lack of sufficient enzymes

Adolescents : improved absorption Geriatrics : diminished absorption due

to depletion of enzymes . Females absorb certain drugs better as

compared to males .eg steroids /hormonal preparations

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Motility of intestine

Metformin is primarily absorbed from the small intestine. The extent of metformin absorption is improved when the gastrointestinal motility is slowed.

Similarly drug absorption is decreased when Motility of intestine is increased in case its absorption is in intestine.

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Gut motility /disease

Gastric Ulcer/duodenal ulcer slow down drug absorption

Diseases like cirrhosis, retard drug absorption

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Gastric emptying

Metoclopramide is a prokinetic agent that stimulates gastric emptying and GI transit .Its mode of action appears to involve antagonism of the inhibitory neurotransmitter dopamine, and increase in acetylcholine release

Propantheline inhibits GI motility and diminishes gastric acid secretion .It is used as an adjunctive therapy in the treatment of peptic ulcer.

The rate and extent of absorption of many drugs are affected by changes in GI motility

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Presence of food Co-administration of drugs with food generally delays drug absorptionDrug-food interactions studies has increased dramatically, and many of the results of these studies have been unpredictable and spectacular. Drug may be affected differently by food when it is administered in different formulations. Drug-food interactions may be classified into five categories: those causing reduced, delayed, increased, and accelerated absorption, and those in which food has no effect.

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Nature of food

Rate of gastric emptying depends primarily on caloric content of ingested meal i.e extent of delay in gastric emptying is the same for proteins ,fats, carbs provided their caloric content is same

Since on molar basis the caloric content of carbs , proteins, fats is different therefore their rate of emptying is also different

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Emptying pattern based on food In general foods, especially fat, can slow gastric

emptying, Carbs empty faster than proteins Proteins empty faster than fats That means 1 . carbs > 2. proteins > 3. fats empty in

this mannerReason for slower emptying of fats is due to the fact

that fats form an oily layer at the top of chyme and therefore digested more slowly by intestinal enzymes

Secondly :-fats promote secretions of bile which in turn decreases gastric emptying. This effect is beneficial for absorption of poorly soluble drugs eg griseofulvin

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Viscosity of ingested meal Liquid meal empties faster from stomach. Bulky or solid materials tend to be slower. Increase in viscosity of gastric contents

reduces the rate of gastric emptying. Therefore fluids pass through stomach very quickly and solids remain until they are well mixed with gastric juice and converted to liquid state .

Increased viscosity delays stomach emptying and hinder drug dissolution

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Volume of meal

Since gastric emptying appears to follow first order kinetics therefore as vol of meal increase there is initial increase in the rate of gastric emptying of gastric contents esp when more fluid is present in stomach

the initial increase in rate of gastric emptying is followed by a decrease in the rate of emptying as the volume of gastric contents decreases

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Volume of meal contd .

More volume more gastric emptying thus better drug absorption and vice versa.

Gastric emptying of liquids in fasted state is a function of volume.

For small volumes less than 100ml Gastric emptying is slower and thus longer.

For large volume greater than 200 ml Gastric emptying begins earlier ,around 10 minutes half life .

Large volume of liquid in stomach help in drug dissolution

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Time of meal

Empty stomach in the morning enhances absorption of antacids.Eg :-

Ampicillin , Bethanechol, Captopril, Rifampin, Sulfadiazine should be taken empty stomach

Anti depressants , sedatives & hypnotics, anti anxiety show enhanced absorption at night

Simvastatin(a hypolipidemic) is preferably consumed at night

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Temperature of ingested material

The temperature of the meal should be same as the temperature of the body 37.50c

Thus the temperature difference between gastric food and drug should be minimum.

very hot meal/ warm food empties better /faster from stomach than cold food

However when temp of ingested food increases to body temp the rate of emptying also increases

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Gastric emptying :effect of drugs

REDUCE RATE OF GASTRIC EMPTYING

Aspirin, anticholinergics ,narcotic analgesics and ethanol

ACIDS in general reduce rate of Gastric emptying (the extent of reduction in rate depends on conc. and mol wt of acid )

Bile salts

ENHANCE THE RATE OF GASTRIC EMPTYING

Alkalies eg NaHCo3

increase rate of gastric emptying at lower conc. But decrease at higher

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Gastric emptying :effect of body posture

Effect of body posture :-

gastric emptying faster in supine position and

Slower in lying position .

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Effect of emotional state /psychological factors Stress, depression

increase gastric motility and rate of gastric emptying

Sleeping on left side delays gastric emptying because the gastric contents have uphill task to empty from the stomach

Vigorous exercise decrease gastric motility and rate of gastric emptying

Sleeping on right enhances due to gravity facilitating in emptying

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Major sites of absorption in GIT :liver; intestine ; stomach

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Summary

Drug Absorption depends on synchronization of all the above

factors .

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References

Book Essentials of medical pharmacology

by K.D TripathyBiopharmaceutics and

pharmacokinetics by P.L.Madan

The internet : Pubmed

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THANK YOU