1. Biopharmaceutics 4th year

2. Factors affecting GI absorption of drug
Dosage Form Factors

3. 1) Disintegration time and Dissolution time
Disintegration time (DT) is important in case of solid dosage form like tablets and capsules.
DT depends on binder present, compression force (hardness).
Drug dissolution is very important factors in drug absorption.

4. 1) Disintegration time and Dissolution time
Factors influencing dissolution of drugs are:
Method of granulation,
compression force,
excipients such as binder, lubricant and Disintegrants

5. 2)Pharmaceutic ingredients (excipients)
Solvent:
aqueous (water , syrup), non aqueous water miscible (PG, glycerol,sorbitol), non aqueous water immiscible (vegetable oil).
aqueous (water , syrup) are miscible with body fluid and drug from them is rapidly absorbed

6. 2)Pharmaceutic ingredients (excipients)
non aqueous water miscible(PG, glycerol,sorbitol) are miscible with body fluid and show better bioavailability
non aqueous water immiscible (vegetable oil) drug absorption depend on its partitioning from oil phase to body fluid

7. 2)Pharmaceutic ingredients (excipients)
Diluents:
Are added to tablet or capsule formulation when the drug dose is inadequate to produce necessary bulk.
Example/ starch, lactose, microcrystalline cellulose, and dicalcium phosphate (DCP)
Tetracycline and DCP produce a complex that is unabsorbable.

8. 2)Pharmaceutic ingredients (excipients)
Binder Are materials used to hold powders together for granulation or produce cohesive form for direct compressible materials and to ensure intact tablet after compression

9. 2)Pharmaceutic ingredients (excipients)
Example/ starch, cellulose derivatives , pvp, gelatin….)
Large amount of binder increase hardness and decrease disintegration/dissolution of tablet
It is found Ethyle cellulose retard drug dissolution.

10. 2)Pharmaceutic ingredients (excipients)
Disintegrant:
These agents are used to overcome the cohesive strength of tablet and break up them when they come in contact with water.
Most of them are hydrophilic, a decrease in their amount may lower bioavailability.

11. 2)Pharmaceutic ingredients (excipients)
Lubricants:
These agent are added to tablet formulation to decrease adhesion or friction of the materials to tablet machine
Example/ zinc stearate or magnesium stearate
If Disintegrant get coated by lubricant it affect disintegration so lubricant are added at final stage before compression.

12. 2)Pharmaceutic ingredients (excipients)
Coating:
The effect of coating materials on dissolution time of drug is in the following order
Enteric coated > sugar coated> non enteric film coated

13. 3) Type of dosage form
The bioavailability of a drug is from various dosage forms decrease in the following order Solution>emulsion>suspension> capsule> tablet> coated tablet > enteric coated tablet>sustained release product

14. 4) Product age and storage conditions
A number of changes especially on physicochemical properties of drug or dosage form can affect bioavailability.
In the case of solution, precipitation of drug or conversion of metastable to poorly stable, stable polymorph may occur
In solid dosage form (tablet , capsule), disintegration and dissolution are affected due to aging and storage condition.

15. Factors affecting GI absorption of drug
Patient Related Factors

16. 1) Age
In infant gastric pH is high, intestine surface area and blood flow is low compared to adult
In elderly persons,
Altered gastric emptying
Decrease surface area
Incident of achlorhydria
Bacterial overgrowth
Causes impaired absorption

17. 2) Gastric Emptying
-Is the passage from the stomach to intestine.
Rapid gastric emptying increase drug bioavailability??

18. Factors affecting gastric emptying
Volume of meal
-Larger bulk of meal, longer gastric emptying
Composition of meal
Gastric emptying is in the following order
carbohydrate> protein>fat
fatty meal delay gastric emptying

19. Factors affecting gastric emptying
Physical state of meal
Liquid materials take 1 hr to empty while solid
materials take 6 hr to empty
Gastrointestinal pH
Gastric emptying is retarded at low pH and promoted at alkaline pH

20. Factors affecting gastric emptying
Electrolyte
Water, isotonic solution , solution of low salt
concentration empty the stomach rapidly
whereas higher electrolyte concentration
decrease gastric emptying rate

21. Factors affecting gastric emptying
Body Posture
Gastric emptying is favored during standing and lying on right side whereas lying on left side or supine position delay gastric emptying
Emotional state
Stress, anxiety promote gastric motility while depression retard it

22. Factors affecting gastric emptying
Exercise
Vigorous physical training may retard gastric emptying
Disease state
-Gastroenteritis, ulcer, pyloric stenosis, diabetes hypothyrodism retard gastric emptying
- hyperthyrodism, gastrectomy duodenal ulcer promote gastric emptying

23. Factors affecting gastric emptying
Drugs
Retard gastric emptying poorly soluble antacids, anticholinergic,tricyclic antidepressant
Metochlorpromide, domperidone stimulate gastric emptying

24. 3)Intestinal Transit
Long intestinal transit is desirable for complete drug absorption

25. 3)Intestinal Transit
-The mixing movement of intestine due peristaltic contraction promote drug absorption by Firstly, increase drug intestinal membrane contact Secondly, by enhancing drug dissolution through agitation

26. 3)Intestinal Transit
Sometimes delay intestinal transit is desirable ,why?
Factors affecting intestinal transit:
Food
Drug
Disease
pregnancy

27. 4)Gastrointestinal pH
GI pH affect drug absorption in different ways:
Disintegration
Dissolution
Absorption
stability

28. 5)Disease state
3 major diseases can influence bioavailability of drug:
Gastrointestinal diseases
Cardiovascular diseases
Hepatic diseases

29. Gastrointestinal Diseases
Altered GI motility
Gastrointestinal infection
Gastrointestinal surgery

30. 6)Blood flow to GI
GIT supplied by blood capillary and lymphatic system Since blood flow to GIT is 500 to 1000 times more than lymph flow Most drugs reach systemic circulation through blood whereas few drugs taken by lymph

31. 6)Blood flow to GI
The high GI perfusion ensures that once the drug has crossed the membrane, it is rapidly removed from the absorption site

32. 7)Gastrointestinal content
A/ Food- Drug Interaction
food interaction may be due to :
Alteration of physiological functions
GI emptying rate , fluid secretions, pH, blood flow

33. 7)Gastrointestinal content
A/ Food- Drug Interaction
food interaction may be due to :
Physicochemical interaction
Alteration of drug dissolution , complexation and adsorption

34. 7)Gastrointestinal content
A/ Food- Drug Interaction As a general rules, drugs are better absorbed under fasting conditions and presence of food retards or prevent it. Foods doesn’t significantly affect a drug taken half an hour or more before meal and two hour or more after meal

35. 7)Gastrointestinal content
A/ Food- Drug Interaction
Delay or decreased drug absorption by food may be due
Delay gastric emptying
Formation of poorly soluble, unabsorbable complex
Increase viscosity thereby prevent drug dissolution

36. 7)Gastrointestinal content
A/ Food- Drug Interaction
Increased drug absorption by food may be due
Increase dissolution time for poorly drug
Enhance solubility due to gastric secretion like bile
Increase lymphatic secretion
Enhance residence time and absorption site contact

37. 7)Gastrointestinal content
A/ Food- Drug Interaction

38. 7)Gastrointestinal content
B/ Fluid Volume Large fluid volume results in better dissolution, rapid gastric emptying, and enhanced absorption. C/ Drug- GI constituent interaction Drug may interact with mucin, bile, enzymes

39. 7)Gastrointestinal content
D) Drug – Drug interaction
Physiological
physicochemical

40. 7)Gastrointestinal content
4) Drug – Drug interaction / Physiological
Antibiotic inhibit bacterial metabolism of drug
-Erythromycin enhance efficacy of digoxin
- Antibiotic co administered with oral contraceptive decrease the efficacy of latter

41. 7)Gastrointestinal content
4) Drug – Drug interaction / Physicochemical
-antidiarrheal containing pectin- kaolin prevent absorption of number of drugs (adsorption)
-Antacids or heavy metal retard absorption of some drugs (complexation)
-basic drugs administered with antacids decrease dissolution rate ( change in pH)

42. 8)Presystemic Metabolism/First –Pass Effects
Before a drug reaches blood circulation, it pass through organs of elimination (GIT and liver)
The loss of drug through biotransformation by such eliminating organs during its passage to systemic circulation is known as first pass effect or presystemic metabolism

43. 8)Presystemic Metabolism/First –Pass Effects
Systems which affect presystemic metabolism of drug are:
Lumenal enzymes
Gut wall enzymes/ mucosal
Bacterial enzymes
Hepatic enzymes

44. 8)Presystemic Metabolism/First –Pass Effects

45. 8)Presystemic Metabolism/First –Pass Effects
Lumenal Enzymes
Hydrolases and Peptidases are enzymes of intestinal and pancreatic secretion
Hydrolases which hydrolyze ester drugs (chloramphenicol palmitate into active chloramphinicol )

46. 8)Presystemic Metabolism/First –Pass Effects
Lumenal Enzymes
Peptidases split amide linkage and inactivate protein or polypeptide drugs.
Approach to effect oral absorption is to deliver them to colon

47. 8)Presystemic Metabolism/First –Pass Effects
B) Gut Wall Enzymes Are enzymes present in stomach, intestine and colon Alcohol dehydrogenase (ADH) which is stomach enzyme inactivate ethanol

48. 8)Presystemic Metabolism/First –Pass Effects
C) Bacterial Enzymes Microflora is present in stomach, small intestine, and is rich in colon most of drugs remain unaffected by them But some drugs convert to active or toxic by colonic microbes

49. 8)Presystemic Metabolism/First –Pass Effects
C) Bacterial Enzymes Sulfasalazine is hydrolyzed to sulfapyridine and 5-amino salicylic acid by microbial enzymes

50. 8)Presystemic Metabolism/First –Pass Effects
D) Hepatic Enzymes Several drugs undergo hepatic metabolism e.g. propranolol

51. The end