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

Π     


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

S  
  
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

Π  



  
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

S  

  
Œecamylamine 11.2 Ionized at all pH values;
Guanethidine 11.7 poorly absorbed from GI6.
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‘ Disintegration time (tablets/capsules)
‘ Dissolution time
‘ Œanufacturing variables
‘ Pharmaceutic ingredients (excipients/adjuvants)
‘ [ature and type of dosage form
‘ Product age and storage conditions
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‘ 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
Ñompression
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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