Lab 2

Question 1

Lipophilicity is also known as _______

Answer 1

hydrophobicity

Question 2

the lipophilicity of a drug greatly affects what?

Answer 2

its distribution in biological tissues

Question 3

the cell membrane consists of…..

Answer 3

2 lipid layers intercepted with some hydrophilic pores

Question 4

What can pass through the hydrophilic pores in the cell membrane?

Answer 4

ONLY small water-soluble molecules can permeate through these pores

Question 5

true or false

the cell membrane is lipophilic

Answer 5

true

Question 6

since the cell membrane is lipophilic, drugs have to be ______ to cross the membrane

Answer 6

drugs have to be sufficiently hydrophobic to cross the membrane

Question 7

most drugs are transferred across the membrane by what process?

Answer 7

passive diffusion

Question 8

the rate of diffusion of drugs through the membrane is dependent on what factors?
(5 of them)

Answer 8

-molecular size
-solubility in the surrounding aqueous phase
-concentration of the drug
-permeability
-tissue blood flow

Question 9

the greater the concentration of the drug at the absorption site, the ______ its absorption

Answer 9

GREATER

Question 10

As mentioned, the greater the concentration of the drug at the absorption site, the greater its absorption.
therefore, the drug must have sufficient…

Answer 10

AQUEOUS solubility

Question 11

true or false

drug permeability decreases with hydrophobicity

Answer 11

FALSE – increases

the drug must diffuse through the lipid membrane

Question 12

for ____ and _____ preparations, the drug must overcome the biological membrane barrier to reach _________

Answer 12

for GI and TOPICAL preparations, the drug must overcome the biological membrane barrier to reach BLOOD CIRCULATION

Question 13

a good drug candidate must have……..

Answer 13

both hydrophilic and hydrophobic properties for ABSORPTION AND DISTRIBUTION in the biological tissue

Question 14

“partition coefficient” is used to express what?

Answer 14

the ability of a drug to distribute itself between TWO IMMISCIBLE SOLVENTS (lipid and aqueous solvents)

Question 15

what is the partition coefficient abbreviated as?

Answer 15

Kpc

Question 16

what is Kpc expressed as?

Answer 16

the ratio of the concentration of the drug in the non-polar lipid phase vs the polar aqueous phase

kpc = conc of drug in lipid phase/conc in drug in aqueous phase

Question 17

the partition coefficient relates to the _____ species of the drug

Answer 17

NEUTRAL (non-ionized or zwitterion)

zwitterion: equal positive and negative charges in a molecule

Question 18

when determining the drug partition coefficient, the drug must be……..

Answer 18

in the SAME CHEMICAL FORM in BOTH SOLVENTS and not react, ionize, or form dimers and complexes with each other

Question 19

the relative solubility of a substance in ___ and ___ is a measure of its lipophilicity

Answer 19

in organic solvent (water-immiscible) and in water

Question 20

what is the most suitable solvent system to test the “in vivo” partitioning ability of a drug?

Answer 20

n-octanol and water

Question 21

n-Octanol is a ______ solvent

Answer 21

NON POLAR

Question 22

How does n-Octanol better mimic a lipid bilayer membrane?

Answer 22

the water content of n-octanol is similar to that of an actual lipid membrane

Question 23

what working with n-octanol, which of its properties must be considered?

Answer 23

it has a very high boiling point (198 degrees celsius).

therefore, in lab experiments, other non polar solvents with low boiling points (such as dichloromethane) are used

Question 24

what is the boiling point of DCM (dichloromethane)

Answer 24

39-40 degrees celsius

Question 25

explain the properties of DCM (dichloromethane)

Answer 25

a colorless, volatile organic solvent NOT miscible in water. has a low boiling point (39-40 degrees celsius) commonly used in extraction procedures

Question 26

besides boiling point, what other property of the solvents used in measuring partition ability must be considered?

Answer 26

the density of the solvents

Question 27

give the order of density of: DCM (dichloromethane) water n-octanol and ethyl acetate

Answer 27

least dense = n-octanol ethyl acetate water most dense = dichloromethane

Question 28

when n-Octanol is used as the non-polar solvent, will water or n-octanol be the bottom layer?

Answer 28

WATER LAYER will be on the bottom because it is more dense

Question 29

for the pharmacokinetic processes of absorption, distribution, and excretion, the drug must be able to distribute itself between what 2 places?

Answer 29

1. Between aqueous extracellular fluids (blood, interstitial fluid, urine) and the lipid membrane 2. Between the lipid membrane and the aqueous cytosol

Question 30

As mentioned, for absorption, distribution, and excretion to occur, the drug must be able to distribute itself between aqueous extracellular fluids and the lipid membrane, as well as between the lipid membrane and aqueous cytosol. in this sense, the drug goes through ______ between.........

Answer 30

PARTITIONING between 2 immiscible aqueous and lipid solvents

Question 31

in general, the drug must be sufficiently lipophilic to passively diffuse through the lipid cell membrane, but what else must be considered?

Answer 31

the drug cannot be so lipophilic that it cannot diffuse into the cytosol or solubilize in the aqueous cell environment

Question 32

________ is an important factor for predicting a drug's pharmacological effects, designing dosage forms, and selecting excipients and routes of administration

Answer 32

PARTITION COEFFICIENT

Question 33

Partition coefficient is useful to predict the......

Answer 33

behavior and fate of drugs in the body

Question 34

true or false highly polar (hydrophilic) drugs are well absorbed in the GI tract and skin

Answer 34

FALSE --- poorly absorbed

Question 35

highly hydrophilic drugs are poorly absorbed in the GI tract and skin. what is the solution to this?

Answer 35

they may need to be administered via IV route

Question 36

true or false lipid drugs (when sufficiently soluble in water) may absorb better in the GI tract than highly hydrophilic drugs

Answer 36

TRUE

Question 37

what can be added to topical dosage forms to improve absorption?

Answer 37

permeability enhancers

Question 38

during drug development, the drug molecular structure is modified to include what?

Answer 38

hydrophobic drugs to improve lipophilcity

Question 39

very hydrophobic drugs have ____ partition coefficient values

Answer 39

HIGH

Question 40

Which type of drugs are able to produce CNS effects? how?

Answer 40

very hydrophobic drugs are able to produce CNS effects because they tend to partition favorable across the lipid BBB (blood brain barrier)

Question 41

Dilution factor formula

Answer 41

Dilution factor = initial volume + diluent volume/initial volume (aka final volume/initial volume)