The document discusses methods for determining intestinal permeability and drug absorption, highlighting human jejunum as the most reliable in vivo method, followed by rat in situ and tissue culture using cell lines like Caco2. It also outlines the gastrointestinal transit times in both fasted and fed states, including examples of drugs like propranolol and atenolol with their permeability, bioavailability, and absorption rates. Additionally, it emphasizes factors predictive of drug absorption, such as solubility, permeability, and gastrointestinal transit.

1. Intestinal Permeability
Determination and Absorption of
soluble drugs
Lecture 5

2. Intestinal Permeability
• Human Jejunum (In Vivo)
– Most Reliable
• Rat In Situ
– Next Most Reliable
• Tissue Culture
– Most Common
• Caco2, MDCK (Epithelial) Cell Lines

3. Tissue Culture

8. Gastrointestinal Transit
• Fasted vs. Fed States
• Gastrointestinal Transit Times
– Rule of ‘3’
• Controlled Release Dosage Forms

9. Transit Rule of ‘3’

19. Examples
• Propranolol
– Peff(Human) = 2.91 x 10-4
cm/sec
– Fabs = 99%
– Bioavailability ~20%.
• Atenolol
– Peff(Human) = 0.3 x 10-4
cm/sec
– Fabs = 42%
– Bioavailability = ~50 %
• Cephalexin
– Peff (Human)= 1.56 x 10-4
cm/sec
– Fabs = 94%
– Bioavailability = ~40%

21. Water Insoluble Drugs
• Metamorphic
limestone
• CaCO3
• Ksp= 9x10-9
= [Ca++
]
[CO3] = x2
• x = solubility = 9.4 x
10 -5
M
• x = 10 µg/ml

30. Predicting Absorption
• Solubility/Dissolution
• Permeability
• Dose
• Transit