Factors of drug absorption

1. PATIENT-RELATING FACTORS AFFECTING ABSORPTION
By,
Souvik Chattopadhyay
M.Pharm, 1st Year
Roll No.- 18HMPS10
Department of Pharmaceutics
Himalayan Pharmacy Institute
Majhitar, East Sikkim-737136

2. Drug absorption is the
movement of a drug into the
bloodstream after
administration. Absorption
affects bioavailability—how
quickly and how much of a
drug reaches its intended
target (site) of action.
Introduction

3. ANATOMY AND PHYSIOLOGY OF GI TRACT
GI TRACT
 The primary function is secretion,
digestion and absorption.
 The mean length of entire GIT is 450cm.
 The main components are stomach, small
intestine and large intestine.
 It is lined by a thin layer of
mucopolysaccharides which act as an
impermeable barrier to particulates such
as bacteria, cells or food particles.

5. Stomach
It is a bag like structure having a smooth muosa and thus small
surface area. Acidic drugs are absorbed in this site due to the
acidic environment caused by HCl.
It is not the principal region for
drug absorption because-
The total mucosal area is small.
The epithelium is dominated by mucus-secreting cells
rather than absorptive cells.
The gastric residence time is limited due to which there is
limited opportunity for gastric uptake of drug.

6. Small Intestine:
It is the major site for absorption of most drugs due to its special characteristics-
• Large surface area :
• Great length of small intestine : results in more than 200sq meters of which is several times that of stomach.
• Greater blood flow: 6 to 10 times more than stomach
• Favourable pH range: 5-7.5
• Slow peristaltic movement : Prolongs residence time of drugs.
• High permeability

7. Large intestine :
1. Length and mucosal surface area is very small in comparison to small intestine.
2. Its contents are neutral or alkaline.

8. PATIENT-RELATED FACTORS
• AGE
This causes absorption alteration due to,
In Infants
• Gastric pH is high
• Intestinal surface is low
• Blood flow to GIT is low
Elderly persons
Altered gastric emptying
Decreased intestinal surface area & GI blood flow
Higher incidents of achlorhydria
Bacterial overgrowth

9. Gastric emptying
DISSOLUTION of a drug & its PERMEATION through the
bio membrane, the passage from stomach to the small
intestine, called as GASTRIC EMPTYING.
• It is the rate limiting step, because the major site of drug
absorption is intestine.
• It increases bioavailability of a drug.
• It is first order process.

10. Situations where rapid gastric emptying recommended:
A.Where Rapid onset of action needed, e.g. Sedatives.
B.Dissolution of drugs occurs in the intestine e.g. enteric-coated
dosage forms.
C. The drugs are not stable in the gastric fluids e.g. penicillin G
and erythromycin.
D.The drug is best absorbed from the distal part of the small
intestine e.g. vitamin B12
Delay in gastric emptying is recommended in particular where:
A. The food promotes drug dissolution and absorption e.g.
griseofulvin.
B. Disintegration and dissolution of dosage form is promoted by
gastric fluids.
C. The drugs dissolve slowly e.g. griseofulvin.
D. The drugs irritate the gastric mucosa e.g. Aspirin,
phenylbutazone and nitrofurantoin.

11. Gastric emptying rate is the speed at which the
stomach contents empty into the intestine.
• Gastric emptying time is the time required for the
gastric content to empty into the small intestine.
• Longer the gastric emptying time , lesser the
gastric emptying rate.
• Gastric emptying t1/2 is the time taken for half
the stomach contents to empty

12. Factors affecting on gastric emptying

14. Intestinal transit
 Small intestine- major site for drug absorption, long intestinal transit is
desirable for complete drug absorption.
 The residence time depends on the intestine that occurs due to peristaltic
contractions..
 It promotes drug absorption by,
a. Increasing drug intestinal membrane contact,
b. Enhancing dissolution especially poorly soluble drugs, through induced
agitation.

15. Delayed intestinal transit is desirable for:
1. Drugs that dissolve or release slowly from their dosage
form (sustained-release products) or when the ratio of
dose to solubility is high e.g. chlorothiazide.
1. Drugs that dissolve only in the intestine (enteric-coated
formulations).
2. Drugs which are absorbed from specific sites in the
intestine like several B vitamins, lithium carbonate etc.
3. When the drug penetrates the intestinal mucosa very
slowly e.g. acyclovir.
4. When absorption of drug from the colon is minimal.

16. Intestinal transit
Promotes..
Diarrhea
Laxatives
Drugs like metoclopramide
Demotes..
Food
Pregnancy
Anticholinergics

17. Gastrointestinal pH
1. Disintegration: pH sensitive. With enteric coated formulations, the
coat dissolves in intestine followed by disintegration of the tablet.
2. Dissolution: A large number of drugs are either weak acids or weak
bases whose solubility is greatly affected by pH. Since the primary
site for absorption of most drug is small intestine, the poorly water
soluble basic drugs first dissolve in the acidic pH of stomach
before moving to intestine.
3. Absorption: Depending upon the drug pKa and whether its an
acidic or a basic drug, the GI pH influences drug absorption by
determining the amount of drug that would exist in the unionized
form at the site of absorption.
4. Stability: GI pH also influences the chemical stability of drugs. The
acidic stomach pH is known to affect degradation of penicillin G
and erythromycin.

18. Blood Flow To The GIT
 The GIT is extensively supplied by blood capillary network & the
lymphatic system.
 The blood flow rate to the GIT is 500 to 1000 times (28% of
cardiac output) more than the lymph flow.
 GI perfusion rate could be a rate limiting step in the absorption of
lipid soluble drugs.
 The perfusion rate increases after meals but absorption is not
influenced significantly.

19. Disease States
Gastrointestinal diseases:
a) Altered GI motility
b) Gastrointestinal diseases and infections: The influence of achlorhydria on gastric emptying and
drug absorption, especially that of acidic drugs has been studied.
Cardiovascular diseases:
 Congestive Heart Failure influence bioavailability of drug viz. edema of intestine,
 Decreased blood flow to the GIT & gastric
emptying rate.
 Altered GI pH, secretion & microbial flora
Hepatic diseases:
 Such as hepatic cirrhosis

20. Presystemic metabolism (First-pass effects)
Before a drug reaches blood circulation, it has to pass for the first time
through organs of elimination namely the GIT and the LIVER. The loss of
drug. through biotransformation by such eliminating organs during· its
passage to systemic circulation is called as first-pass or presystemic
metabolism
The 4 primary systems which affect presystemic
metabolism of a drug are (Fig. 2.24):
I. Lumenal enzymes,
2. Gut wall enzymes/mucosa) enzymes,
3. Bacterial enzymes, and
4. Hepatic enzymes.

21. 1. Lumenal enzymes : These are the enzymes present in the gut fluids and include enzymes
from intestinal and pancreatic secretions. The latter contains hydrolases which hydrolyze ester
drugs like chloramphenico1 palmitate into active chloramphenicol, and peptidases which split
amide linkages and inactivate protein/polypeptide drugs.
2. Gut wall enzymes : Also called as mucosal enzymes, they are present in stomach, intestine
and colon. Alcohol dehydrogenase (ADH) is an enzyme of stomach mucosa that inactivates
ethanol.
3. Bacterial enzymes : The GI microflora is scantily present in stomach and small intestine and
is rich in colon. Hence, most orally administered drugs remain unaffected by them. The colonic
microbes generally render a drug more active or toxic on biotransformation for example
sulfasalazine, a drug used in ulcerative colitis, is hydrolyzed to sulfapyridine and 5-amino
salicylic acid by the microbial enzymes of the colon.

24. Reference
1. Biopharmaceutics and Pharmacokinetics-A Treatise: Brahmankar & Jaiswal, 3rd
Edition(2014)
2. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-
pharmaceutical-science/drug-absorption