Physicochemical Properties III

Question 1

What happens when a drug is too hydrophilic?

Answer 1

Good water solubility

Poor membrane penetration

Question 2

What happens when a drug is too lipophilic?

Answer 2

Good membrane penetration

Poor water solubility

Question 3

How can solubility issues be fixed?

Answer 3

Salt formation

Chemical modification by adding polar groups like -OH, NH2, etc.

Question 4

How can lipophilicity issues be fixed?

Answer 4

Chemical modification by addition of lipophilic groups

Masking of polar groups by nonpolar groups.

Question 5

What is a dipole bond?

Answer 5

Results from unequal sharing of electrons between atoms within a covalent bond.

Question 6

Generally the greater number of hydrogen bonds a molecule has the greater the solubility except when?

Answer 6

Except when there are intramolecular hydrogen bonds. Intramolecular hydrogen bonds decrease solubility and increase lipid solubility.

Question 7

Compounds capable of intramolecular ionic interactions have very high or low solubility? What is an example of this?

Answer 7

Low solubility

Tyrosine

Question 8

Strong acids and strong bases make what when they interact?

Answer 8

salt and water

Question 9

What happens when weak acids interact with strong bases?

Answer 9

A molecular salt may be formed.

Question 10

What are some examples of weekly acidic drugs?

Answer 10

Carboxylic acids, sulfonamides, imides, phenols

Question 11

What are some examples of strong bases?

Answer 11

Sodium hydroxide (NaOH), potassium hydroxide (KOH), calcium hydroxide (Ca(OH)2)

Question 12

What is the original acidic drug and identify the base:

Sodium sulfisoxazole

Answer 12

NaOH

sulfisoxazole

Question 13

What is the original acidic drug and identify the base:

aluminum aspirin

Answer 13

Aluminum Hydroxide

aspirin

Question 14

What is the original acidic drug and identify the base:

phenobarbital sodium

Answer 14

NaOH

phenobarbital

Question 15

What is the original acidic drug and identify the base:

Penicillin V Potassium

Answer 15

KOH

Penicillin

Question 16

What makes up a salt of molecular bases?

Answer 16

Weakly basic drugs with a strong acid.

Basic drugs with organic acids

Question 17

What are weakly basic drugs?

Answer 17

Amines

Question 18

What are strong acids?

Answer 18

Hydrochloric acid (HCl), Hydrobromic acid (HBr), Sulfuric acid (H2SO4), Nitric acid (HNO3)

Question 19

What is the original basic drug and identify the acid:

Pseduoephedrine Hydrochloride

Answer 19

HCl

Pesudoephedrine

Question 20

What are examples of organic acids?

Answer 20

Maleic, fumaric, tartaric, succinic, and citric acid

Question 21

Low molecular weight salts are more or less water soluble than high molecular weight salts?

Answer 21

More water soluble

Question 22

Therapeutic salts marketed for aqueous injection are commonly:

Answer 22

Weak organic acidic drugs with strong bases (e.g. a metal hydroxide)
Weak organic basic drugs with strong acids (e.g. mineral acids)

Question 23

Ionized acids and bases if added together in water, have the capacity to interact in?

Answer 23

proton transfer reaction.

Question 24

Why can proton transfer be dangerous?

Answer 24

The unionized species would be water insoluble and precipitate out in the syringe or in the IV line.
No drug will be delivered
Risk of injecting particulate matter into the bloodstream if the drugs were being given IV.

Question 25

What are some reasons predicted incompatibility may not occur in practice?

Answer 25

The unionized conjugates have many polar functional groups capable of hydrogen bonding with water, which would allow the unionized forms to remain soluble. The concentration of the drugs in solution is very dilute. The solution is buffered to maintain a pH that allows the agents to remain in ionized, water soluble form.

Question 26

Predict whether this pair of water soluble drugs would be chemically compatible or incompatible: Alfentanil hydrochloride and Morphine Sulfate

Answer 26

Compatible

Question 27

Predict whether this pair of water soluble drugs would be chemically compatible or incompatible: Acyclovir Sodium and Morphine Sulfate

Answer 27

Incompatible

Question 28

Predict whether this pair of water soluble drugs would be chemically compatible or incompatible: Butorphanol Tartrate and Morphine Sulfate

Answer 28

Compatible

Question 29

Predict whether this pair of water soluble drugs would be chemically compatible or incompatible: Pantoprazole Sodium and Morphine Sulfate

Answer 29

Incompatible

Question 30

What are the two approaches to water solubility predictions?

Answer 30

Empiric Approach | Analytical Approach

Question 31

What is the empiric approach?

Answer 31

Molecule is considered to be water soluble when: the solubilizing potential of the functional groups is greater then the total number of carbon atoms presents. Salt forms increases solubilizing potential by difficult to quantitate 20 to 30 carbons.

Question 32

What is the analytical approach?

Answer 32

Lipophilicity and LogP(partition coefficient for a molecule)

Question 33

What does the LogP mean?

Answer 33

The molecules affinity for octanol over water. The higher the LogP the more lipophilic it is.

Question 34

What is the LogP range to penetrate the Blood Brain Barrier (BBB)?

Answer 34

1.5 to 2.7 with an average of 2.1

Question 35

What are examples of drugs that are common CNS targeted therapeutic agents?

Answer 35

Carbamazepine(Tegretol) | Phenobarbital(Luminal)

Question 36

What beta blocker penetrates the BBB and may induce disturbing CNS side effects?

Answer 36

propranolol(ClogP 2.65) not atenolol (ClogP 0.5)

Question 37

What are the effects of lipophilicity on drug absorption as shown in Enalaprilat (Vasotec IV) and Enalapril (Vasotec)?

Answer 37

Enalaprilat has a ClogP value of 1.17, oral bioavailability of 30-40%, and is administered by IV route. Enalapril has a ClogP value of 1.77, oral bioavailability of 50-70%, and is administered orally. Also a Prodrug.

Question 38

What enzyme is enalapril activated by?

Answer 38

hepatic esterases, ester turns into carboxylic acid

Question 39

What drug was made into a sustained-release using increased lipophilicity?

Answer 39

Haloperidol (ClogP 3.49) was made into Haloperidol deconate (ClogP 7.3) which was taken into fatty tissues and slowly released over time. Haloperidol deconate is a prodrug.