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m Drug-solubility and dissolution rate

m Particle size and effective surface area

m Polymorphism and amorphism
m Pseudopolymorphism (hydrates/solvates)
m Salt form of the drug
m Lipophilicity of the drug
m Drug pKa and pH
m Drug stability



‘ 6he pH partition theory (for molecular weight greater
than 100) explain the process of absorption of drug is
governed by:
m 6he dissociation constant (pKa) of the drug.
m 6he lipid solubility of the unionized drug (a function
of drug Ko/w)
m 6he pH at the absorption site.

hypothesis was based on the Ê that:
m 6he GI6 is a simple lipoidal barrier to the transport of
m Larger the fraction of unionized drug, faster the
m Greater the lipophilicity (Ko/w) of the unionized drug,
better the absorption.
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6  pKa 
Pentobarbital 8.1 Unionized at all pH values
Hexobarbital 8.2 absorbed along the entire length of GI6
Phenytoin 8.3
Ethosuximide 9.3


Ñloxacillin 2.7 Unionized in gastric pH and
Aspirin 3.5 ionized in intestinal pH; better
Ibuprofen 4.4 absorbed from stomach
Phenylbutazone 4.5

Disodium cromoglycate 2.0 Ionized at all pH values; poorly
Absorbed from GI6

6heophylline 0.7 Unionized at all pH values
Ñaffeine 0.8 absorbed along the entire length of GI6
xazepam 1.7
Diazepam 3.7


½eserpine 6.6 Ionized at gastric pH,
Heroin 7.8 relatively unionized at intestinal pH;
Ñodeine 8.2 better absorbed from intestine.
Arnitriptyline 9.4


Œecamylamine 11.2 Ionized at all pH values;
Guanethidine 11.7 poorly absorbed from GI6.


‘ Disintegration time (tablets/capsules)
‘ Dissolution time
‘ Œanufacturing variables
‘ Pharmaceutic ingredients (excipients/adjuvants)
‘ [ature and type of dosage form
‘ Product age and storage conditions


‘ Disintegration time (D6)(tablets/capsules)
D6 Dissolution Absorption Bioavailability
sugar coated tablet have long D6
D6 of tablet dependent on binder/Ñompression Force (Hardness)
Disintegration is increase by using disintegrants agent
‘ Œanufacturing variables
Œethod of granulation
Wet granulation Dissolution more as compare to Dry granulation
Influence porosity, density, hardness, D6 and dissolution
Higher compression
‘ Pharmaceutic ingredients (excipients/adjuvants)
¦ehicle Ȃ Aqueous
[on aqueous water misible
[on aqueous water immiscible
  6! "
Include factors relating to the anatomical physiological and
pathological characteristics of the patient
‘ Age
‘ Gastric emptying time
‘ intestinal transit time
‘ Gastrointestinal pH
‘ Disease states
‘ Blood flow through the GI6
‘ Gastrointestinal contents
First Pass Œetabolism

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