biomed quiz 2-3 Flashcards
lipophilicity (hydrophobic)
cell membrane- 2 lipid bilayers
cell membrane
cell membrane is lipophilic (hydrophobic) hence drugs have to be sufficiently hydrophobic to cross the membrane.
Most drugs are transferred across the membrane
by passive diffusion
the rate of diffusion is dependent on several factors:
-molecular size
-solubility in the surrounding aqueous phase
-the concentration of the drug
-permeability
-tissue blood flow
The greater the concentration of the drug at the absorption site,
the greater is its absorption
Drug permeability, on the other hand, increases with
hydrophobicity as the drug must diffuse through the lipophilic cell membrane.
For gastrointestinal and topical preparations, the drug must overcome the biological membrane barrier to reach blood circulation
A good drug candidate must have both hydrophilic and hydrophobic properties for absorption and distribution in the biological tissue.
true
The relative solubility of a substance an organic solvent (water-immiscible) and in water is a measure of its lipophilicity.
The term “partition coefficient”
is used to express the ability of a drug to distribute itself between two immiscible (lipid and aqueous) solvents.
The partition coefficient (abbreviated as Kpc) is given as the ratio of the concentration of the drug in the non-polar lipid phase vs the polar aqueous phase.
The partition coefficient relates to the neutral (non-ionized or zwitterion) species of the drug.
n-Octanol
n-Octanol is a non-polar solvent that better mimics a bilayer lipid membrane because the water content of n-octanol is similar to that of the membrane. However, the boiling point of n-octanol is high (198°C); therefore, in lab experiments, other non-polar solvents with low boiling points such as dichloromethane (boiling point from 39°C to 40°C) are used.
n-Octanol is a hydrophobic, nonpolar solvent that is less dense than water. In liquid-liquid extractions, substances tend to separate based on their solubility in the different phases. Since n-octanol is less dense than water, it will float on top of the water layer, and the water layer will be at the bottom.
DCM
Dichloromethane is a colorless and volatile organic solvent that is not miscible in water commonly used in extraction procedures
ORDER
The order of density of some solvents is n-octanol < ethyl acetate < water < dichloromethane. It is important to remember that when n-Octanol is used as the nonpolar solvent, the water layer will be the bottom layer.
The drug must be able to distribute itself:
1) between aqueous extracellular fluids (blood, interstitial fluid, urine) and lipid membrane
2) between lipid membrane and aqueous cytosol.
Partition coefficient
Its pharmacological effects, designing, dosage forms, and selecting excipients and routes of administration.
The partition coefficient is useful to predict the behavior and fate of drugs in the body. Highly polar (hydrophilic drugs) are poorly absorbed in the GI tract and skin and may need to be administered via the IV route.
Lipid soluble drugs may be better absorbed in the GI tract when they are sufficiently soluble in the aqueous environment
Permeability enhancers may be needed in topical dosage forms to improve absorption
uring drug development, the drug molecular structure is modified to include hydrophobic groups that improve lipophilicity.
HIGH LOGP
Very hydrophobic drugs have high partition coefficient values and tend to partition (cross) favorably across the lipid blood-brain barrier to produce CNS effects.
