Topic 3 - Absorption of Drug Properties Flashcards
Steps of oral absorption (applicable to tablets)
- Disintegration
- Diffusion into GI fluid
- Partitioning into GI membrane
- Diffusion thru/transport across memb
- Partitioning into blood stream
- Transport away by blood
What are the 2 main mechanisms of transport across the GI membrane?
- Paracellular diffusion (around cells)
- Transcellular diffusion (through - passive, carrier-mediated)
Describe passive diffusion vs. active diffusion absorption rate profile
Passive: constant and positive slope between drug concentration at absorption site and rate of absorption
Active, with transported: curve increases, then plateaus, as all the carriers are saturated with drug
Solubility
Extent to which a drug dissolves under a given set of cond’ts of solvent and temperature
Intrinsic dissolution rate constant (IDR)
Compare drugs independent of surface area.
What does an IDR < 0.1 mean? If it’s not ideal, what should it be to make it ideal?
0.1 = exhibit dissolution-limited adsorption
> 1 = okay (works well)
Factors influencing the saturation concentration (5)
- Crystal structure
- pH
- Salt form
- Common ion effect
- Co-solvents
Crystalline solids characteristics (3)
- Regular, ordered structure composed of identical repeating units
- Distinct melting points, Tf
- Strength of bonds between atoms
The stronger the lattics…
Higher Tf > Slower rate of dissolution
What kind of structures do electrostatic and covalent bonds create?
Stable structures that are hard and brittle.
What kind of structures do Van der Waals and H-bonds create?
Soft materials and metastable structures
Polymorphism
Drug can reform depending on different conditions, or crystallize into more than one crystal structure.
T/F: Dissolution rate changes with polymorphic form
T
What is amorphism?
No presence of structure. For drugs, no distinct melting temp, and structures can flow under applied P. They are generally easier to dissolve.
Crystal hydrates
Structures in which solvents are trapped when compound crystallizes (solvates)
Hydrates vs. anhydrate
Hydrate: Crystal hydrate when the solvent is water
Anhydrate: Solvent is not water
T/F: Hydrates generally dissolve faster
F: Anhydrates do (but not always)
How does water affect the drug lattice structure?
Water may weaken or strengthen the lattice. In the case of strengthening, H-bonds may form which stabilizes the structure more.
pHp
pH below which the drug precipitates from solution
What is the difference between Ko/w and Kapp?
Kapp considers the fact that the majority of drugs are ionizable, so it accounts for the ion distribution. Ko/w only considers the amount of drug in the cell vs. blood.
What is the “common ion” effect?
Presence of a common ion may reduce solubility (ie. tetracycline HCl in the stomach, which already has HCl in it)
Co-solvents
Solvents that increase the solubility of a given compound when combined
