First pass effect Gastric emptying time Gastrointestinal motility Short note on Gastric emptying and motility Physicochemical factors affecting drug absorption A. Drug solubility and dissolution rate B. Particle size and surface area of drugs C. Polymorphism and amorphism D. Hydrate or solvates Biopharmaceutical classification system of drug

1. I N T R O D U C T I O N TO
B I O P H A R M A C E U T I C S
PA RT: 4

2. CONTENTS
• First pass effect
• Gastric emptying time
• Gastrointestinal motility
• Short note on Gastric emptying and motility
• Physicochemical factors affecting drug absorption
A. Drug solubility and dissolution rate
B. Particle size and surface area of drugs
C. Polymorphism and amorphism
D. Hydrate or solvates
• Biopharmaceutical classification system of drug

3. FIRST PASS EFFECT
• First pass effect (also known as first pass
metabolism or pre-systemic metabolism) of is
a phenomenon of drug metabolism whereby
the concentration of a drug specifically when
administered orally, is greatly reduced before
it reaches the systemic circulation.
• The four primary system that affect the first
pass effect of a drug are the enzyme of the GI
lumen, gut wall enzyme, bacterial enzyme
and hepatic enzyme.

4. GASTRIC EMPTYING TIME
• The time required for gastric content to empty into small intestine is
called gastric emptying time.
• A delay in the gastric emptying time for the track to reach the
duodenum will slow the rate and possibly the extent of drug
absorption, thereby prolonging the onset time for the drug.

5. GASTRIC EMPTYING IS RETARDED BY
• Fat and fatty acid in the diet
• High concentration of electrolytes
• Mental depression
• Lying on the left side
• Disease e.g gastric ulcer, hypothyroidism diabetics etc.
• Many drugs e.g. atropine, chlorpromazine etc.

6. GASTRIC EMPTYING IS PROMOTED BY
• Fasting or hunger
• Anxiety
• Alkaline buffer solution
• Lying on the right side
• Disease e.g hyperthyroidism
• Drug e.g metoclopramide

7. GASTROINTESTINAL MOTILITY
- Once a drug is given orally, the exact location or
environment of the drug product within the GIT is difficult
to determine.
- GI movement tends to move the drug through the
alimentary canal, so the drug may not stay at the absorption
site is called GI motility.

8. Short note:
(Gastric emptying and motility:
- The time a dosage form takes to traverse the stomach is usually termed: the
gastric residence time, the gastric emptying time or gastric emptying rate.
- Generally drugs are better absorbed in the small intestine (because of the larger
surface area) than in the stomach, therefore quicker stomach emptying will
increase drug absorption.
- For example, a good correlation has been found between stomach emptying
time and peak plasma concentration for acetaminophen. The quicker the
stomach emptying (shorter stomach emptying time) the higher the plasma
concentration.
• Also slower stomach emptying can cause increased degradation of drugs in the
stomach's lower pH; e.g. L-dopa. Emptying time) the higher the plasma.)

9. PHYSICOCHEMICAL FACTORS
AFFECTING DRUG ABSORPTION
A. Drug solubility and dissolution rate,

10. • Dissolution rate: Amount of solid substance that goes into solution per unit
time under standard conditions of temperature, pH and solvent composition and
constant solid surface area.
• For Hydrophobic drugs: Dissolution is rate limited step. eg griseofulvin,
spironolactone.
• For Hydrophilic drugs: Permeation is rate limited step. eg cromolyn sodium,
neomycin.

11. BIOPHARMACEUTICAL
CLASSIFICATION SYSTEM OF DRUG:
Class Solubility Permeability Absorption
pattern
Rate
limiting step
in
absorption
Examples
1 High High Well
absorbed
Gastric
emptying
Diltiazem
2 Low High Variable Dissolution Nifedipine
3 High Low Variable Permeability Insulin
4 Low Low Poorly
absorbed
Case to case Paclitaxel

12. B. Particle size and surface area of drugs:

13.  Smaller the particle size (by micronization) greater is the effective surface
area more intimate contact b / w solid surface and aq solvent higher is the
dissolution rate increase in absorption efficiency.
 Particle size reduction has been used to increase the absorption of a large
number of poorly soluble drugs, such as bis-hydroxycoumarin, digoxin,
griseofulvin, nitrofurantoin, and tolbutamide.
 Griseofulvin has extremely low aqueous solubility, and material of normal
particle size gave rise to poor and erratic absorption.
 Microsize particles improve absorption, but it is improved even more when it
is formulated in ultramicrosize particles as a monomolecular dispersion in
polyethylene glycol.

14. C. Polymorphism and amorphism:
- Many compounds form crystals with different molecular arrangements, or
polymorphs.
- These polymorphs may have different physical properties, such as dissolution
rate and solubility.
 40% of all organic compounds - exist in various polymorphic forms.
• 70% of barbiturates & 65% of sulphonamides exhibit polymorphism.

15. Amorphous form:
These have greater aqueous solubility than the crystaline
forms because the energy required to transfer a molecule from crystal
lattice is greater than that required for non-crystalline solid.
eg: amorphous form of novobiocin - 10 times more soluble
than crystalline form.
amorphous> metastable> stable

16. D. HYDRATE OR SOLVATES
- The stoichiometric type of adducts where the solvent molecule are
incorporated with the crystal lattice of the solid are called as solvates.
- Trapped solvent is the solvent of crystallization.
- The solvates can exist in diff crystalline forms called as pseudomorphs
and the phenomenon is pseudopolymorphism.
- When the solvent in association with drug is water, the solvate is
known as hydrate.

18. …….T0 BE CONTINUED…..
•.....Last part will be published on 22/04/2021…..