factor influencing Drug absorption see the slide ..

1. SUBMITTED TO : SUBMITTED BY
DR. SUDIPTA SAHA. MD ASIF ZAWED
ASST. PROFESSOR MPHARM 1ST YEAR
(PHARMACOLOGY).
DEPARTMENT OF PHARMACEUTICAL SCIENCE ,BABASAHEB BHIMRAO
AMBEDKAR UNIVERSITY , LUCKNOW, 226025.

2. Contents:
 INTRODUCTION
 ABSORPTION OF DRUGS.
DIFFERENT ROUTE OF DRUG ADMINISTRATION AND THERE ABSORPTION
FACTOR INFLUENCING THE GASTRO INTESTINAL DRUG ABSORPTION
A. PHARMACEUTICAL FACTORS:
I. PHYSIOCHEMICAL PROPERTIES OF DRUG SUBSTANCE
II. DOSAGE FORM AND PHARMACEUTICAL INGREDIENT
B. PATIENT RELATED FACTOR:

3. INTRODUCTION
Effect needed

4. • Defined as the process of transport of unchanged drug from the
site of administration to the systematic circulation by crossing
biological membrane.
Plasmaconcentration
• Why drug should
be Transported ?
• In order to reach
his receptor And
produce
biological Effect.

5. CONT …
INTRAVENOUS ADMINISTRATION HAS NO ABSORPTION PHASE
ACCORDING TO THE RATE OF ABSORPTION:
INHALATION→ SUBLINGUAL→ RECTAL→ INTRAMUSCULAR→
SUBCUTANEOUS→ ORAL→ TRANSDERMAL

6. The rate and extent of drug absorption called bioavailability.

7. A. PHARMACEUTICAL FACTORS:
I. PHYSIOCHEMICAL PROPERTIES OF DRUG SUBSTANCE
a) DRUG SOLUBILILTY AND DISSOLUTION RATE
b) PARTICLE SIZE SURFACE AREA
c) POLYMORPHISM AND AMORPHISM
d) SALT FORM OF THE DRUG
e) LIPOPHILICITY OF THE DRUG
f) pKa OF THE DRUG AND GI PH
g) DRUG STABILITY
h) STERIOCHEMICAL NATURE OF THE DRUG
II. DOSAGE FORM AND PHARMACEUTICAL INGREDIENT
a) DISINTIGRATION TIME
b) DISSOLUTION TIME
c) MANUFACTURING VARIABLES
d) NATURE AND TYPE OF DOSAGE FORM
e) PRODUCT AGE AND STORAGE CONDITION

8. Drug in
solution at the
absorption
site.
Fine particles
Granules or
aggregates
Solid dosage
form
Non ionised
drugs
Ionised
drugs
C
E
L
L
M
E
M
B
R
A
N
E
ionised
drugs
Non
ionised
drugs
D
I
S
S
O
L
U
T
I
O
N
G.I. LUMEN BLOOD
ABSORPTIO
N
For Hydrophobic drugs:
Dissolution is rate limited step.
eg: griseofulvin , spironolactone.
For Hydrophilic drugs:
Permeation is rate limited step.
eg: cromolyn sodium, neomycin

9. CONT…
• DISSOLUTION IS A PROCESS IN WHICH A SOLID SUBSTANCE SOLUBILISE IN A GIVEN SOLVENT
1. DIFFUSION LAYER MODEL / FILM THEORY
2. INTERFACIAL BARRIER MODEL.
3. PENETRATION OR SURFACE RENEWAL THEORY.
DIFFUSION LAYER MODEL/OR FILM THEORY
SIMPLEST AND MOST COMMON PROCESS FOR DISSOLUTION.
1. SOLUTION OF THE SOLID TO FORM A THIN FILM OR LAYER AT THE SOLID LIQUID
INTERFACE CALLED THE STENGENT FILM OR DISSOLUTION FILM OR DISSOLUTION LAYER .
THIS STEP IS USUALLY RAPID.
2. DIFFUSION OF THE SOLUBLE SOLUTES FROM THE STENGENT LAYER TO THE BULK OF THE
SOLUTION ..THIS STEP IS SLOWER AND IS THEREFORE THE RATE DETERMINING STEP IN
DRUG DISSOLUTION.

10. PARTICLE S SIZE AND SURFACE AREA OF A SOLID DRUGS ARE INVERSELY RELATED TO EACH
OTHER
SMALLER PARTICLE SIZE-> GREATER SURFACE AREA->RAPID DISSOLUTION
MICRONIZATION –GRATER SURFACE AREA-RAPID DISSOLUTION OF HYDROPHILIC DRUGS
EG:-GRISEOFULVIN, SPIRANOLACTONE
HYDROPHOBIC DRUGS-MICRONIZATION-DECREASE IN EFFECTIVE SURFACE AREA-FALL IN
DISSOLUTION RATE
CAUSES
• ADSORPTION OF AIR TO SURAFCE
• PARTICLE REAGGREGATION
• SURFACE CHARGE
EG:- ASPIRIN , PHENACETIN
IN THAT CASE ADD- SURFACTANTS –TWEEN 80

11.  POLYMORPHISM
WHEN SUBSTANCE EXISTS IN DIFFERENT
CRYSTALLINE FORMS, IT IS POLYMORPHISM.
AMORPHISM
• THESE DRUGS CAN EXIST WITH NO INTERNAL CRYSTAL STRUCTURE.
• SUCH DRUG REPRESENTS THE HIGHEST ENERGY STATE AND CAN BE CONSIDERED AS
SUPER COOLED LIQUIDS AND THUS HAVE GREATER SOLUBILITY. E.G. NOVOBIOCIN.
• THUS, THE ORDER OF DISSOLUTION & HENCE ABSORPTION FOR DIFFERENT SOLID
DOSAGE FORMS IS AMORPHOUS > META-STABLE > STABLE.
Plot of Cp Vs Time for three
formulations of
Chloramphenicol Palmitate

12. 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 AND THE
DISSOLUTION THUS CAN BE IMPROVED.
Fig 1. It shows the
dissolution
Profile of various salts

13. ACCORDING TO PH PARTITION THEORY, THE PROCESS OF ABSORPTION OF DRUG
COMPOUNDS OF MOLECULAR WEIGHT GREATER THAN 100 DALTONS
TRANSPORTED ACROSS THE BIOMEMBRANE BY PASSIVE DIFFUSION DEPEND UPON
THE FOLLOWING FACTOR
 DISSOCIATION CONSTANT OF THE DRUG I.E., PKa OF THE DRUG
 LIPID SOLUBILITY OF THE UNIONIZED DRUG.
 PH AT THE ABSORPTION SITE
THE AMOUNT OF DRUG THAT EXIST IN UNIONIZED FORM IS A FUNCTION OF
DISSOCIATION CONSTANT(PKA) OF THE DRUG AND PH OF THE FLUID AT THE
ABSORPTION SITE.
FOR WEAK ACIDS FOR WEAK BASE

14. Conti…
FOR WEAK ACIDS
VERY WEAK ACIDS(PKA>8)– UNIONIZED AT ALL PH—ABSORPTION IS RAPID—
INDIPENDANT OF GI PH
 EG:-PHENYTOIN , ETHOSUXIMIDE
ACIDS IN THE PKA RANGE 2.5 TO 7.5 LARGELY AFFECTED BY PH CHANGE—
ABSORPTION PH DEPENDANT—BETTER ABSORBED FROM ACIDIC CONDITIONS OF
STOMACH (PH<PKA)WHERE THEY LARGELY EXIST IN UNIONIZED FORM
EG:-ASPIRIN , IBUPROFEN
STRONG ACIDS (PKA<2.5) IONIZED AT ENTIRE PH RANGE OF GIT ---REMAIN
POORLY ABSORBED
EG:-CROMOLYN SODIUM

15. Conti…
FOR BASIC DRUGS
1. VERY WEAK BASES(PKA<5) UNIONIZED AT ALL PH VALUES ---ABSORPTION IS
RAPID AND PH INDIPENDANT
EG:-DIAZEPAM , NITRAZEPAM
2. BASES IN PKA RANGE 5 TO 11 IS PH DEPENDANT –BETTER ABSORBED FROM THE
RELATIVELY ALKALINE CONDITIONS OF THE INTESTINE
EG:-CHLOROQUINE , IMIPRAMINE
3. STRONG BASES (PKA>11) IONIZED AT ENTIRE PH RANGE –POORLY ABSORBED
EG:-MECAMYLAMINE GUANETHIDINE

16. • ONLY UNIONIZED DRUG HAVING SUFFICIENT LIPID SOLUBILITY IS ABSORBED INTO
SYSTEMIC CIRCULATION.
• SO DRUG SHOULD HAVE SUFFICIENT AQUEOUS SOLUBILITY TO DISSOLVE IN THE FLUIDS
AT THE ABSORPTION SITE AND LIPID SOLUBILITY HIGH ENOUGH TO FACILITATE THE
PARTITIONING OF THE DRUG IN LIPOIDAL MEMBRANE AND INTO SYSTEMIC
CIRCULATION.
• TWO MAJOR STABILITY PROBLEMS ARE
• 1.DEGRADATION OF THE DRUG INTO INACTIVE FORM
• 2.INTERACTION WITH ONE OR MORE COMPONENT EITHER OF THE DOSAGE FORM OR
THOSE PRESENT IN THE GIT TO FORM A COMPLEX THAT IS POORLY SOLUBLE

18. CONT…
a) AGE
b) GASTRIC EMPTYING
a) VOLUME OF MEAL
b) COMPOSITION OF MEAL
c) PHYSICAL STATE AND VISCOSITY OF MEAL
c) INTESTINAL TRANSIT TIME
d) G.I pH
e) DISEASE STATE
f) BLOOD FLOW THROUGH THE GIT
g) GI CONTENTS
• OTHER DRUGS
• FOOD
• FLUIDS etc…

19. • BRAHMANKAR D.M;JAISWAL SUNIL.B; “BIOPHARMACEUTICS AND
PHARMACOKINETICS–A TREATISE, SECOND EDITION 2009.
• GOODMAN AND GILMAN'S THE PHARMACOLOGICAL BASIS OF
THERAPEUTICS (12TH EDITION)