EXAM2 L5

Question 1

Review equations for solubility for weak acid (can’t format properly on here)

Answer 1

Slide 26-28

Question 2

If pH«pKa, solubility is nearly ______ of pH

Answer 2

independent

Question 3

T/F: Solubility increases as pH decreases

Answer 3

False; solubility increases as pH increases

Question 4

T/F: Indefinite solubility increase is truncated by precipitation of a salt

Answer 4

True; (diff. salts have different solubilities)

Question 5

Crystalluria is

Answer 5

The formation of crystals in the urine

Question 6

pH of urine

Answer 6

4.5-8

Question 7

Ionized compounds are/are not reabsorbed in distal tubule?

Answer 7

Are not

Question 8

Rate of clearance cant be impacted by urine pH due to

Answer 8

Variation in ionization state of drug

Question 9

T/F: Urine pH can be deliberately altered (i.e. by admin. of sodium bicarbonate) in order to enhance or retard clearance

Answer 9

True

Question 10

Enteric coating

Question 11

A salt is formed by

Answer 11

Acid base reaction involving either proton donation or proton acceptance

Question 12

Typical Pharmaceutical salts

Answer 12

Strong acid + Strong Base
Strong Acid + Weak Base
Weak acid + Strong Base
Weak Acid + Weak Base

Question 13

What % of drugs are administered as salts?

Answer 13

50%

Question 14

Salt formation modifies what properties of drugs?

Answer 14

Solubility, crystallinity, particle size, bulk, density

Question 15

Common reasons for salt formation

Answer 15

Bioavailability
Developability
Purification
Intellectual property

Question 16

Rule of thumb of salt formation

Answer 16

pKa difference between acid and base should be at least 2-3 units

Question 17

Different Salts may ne used for different formulations ex.

Answer 17

Capsule
Injection
Suspension
Acid
Na
Mg

Question 18

Region 1 Solid Phase: Free Acid characteristics

Answer 18

Solubility depends on properties of acid

Question 19

Region 2: Solid phase salt Characteristics

Answer 19

Solubility depends on properties of salt

Question 20

Hydrophilic compounds have positive/negative log P values

Answer 20

Negative (Hydrophobic has Positive Log P)

Question 21

T/F: True partition coefficient P, applies only when the species distributing between each phase is the same (i.e. both are unionized species)

Answer 21

True

Question 22

pH Partition Hypothesis parts

Answer 22

GI/blood barrier acts as a lipid battier to weak electrolyte drugs that are absorbed by passive absorption
ONLY unionized drugs will pass through GI membrane
Ionized form is NOT SOLUBLE in lipid phase

Question 23

Apparent partition coefficient for a weakly acidic drug as a function of pH

Answer 23

Higher pH - becomes more ionized
Higher total concentration in aqueous phase
Lower apparent partition coefficient

Question 24

Ion trapping in the stomach can lead to

Answer 24

Gastric mucosal cell damage (i.e. aspirin)

Question 25

T/F: Acids show better absorption than bases in stomach

Answer 25

True

Question 26

T/F: Weak bases will not be absorbed from stomach

Answer 26

True

Question 27

T/F: Bases show better absorption than strong acids in the small intestine

Answer 27

True

Question 28

Limitations of pH-partition hypothesis

Answer 28

GI compartments and blood are not static therefore no equilibrium obtained Weak acids still quite well absorbed from intestine due to high intestinal SA Anionic drugs have some permeability May be absorbed via specific transporters, or via a paracellular route

Question 29

Extraction Process

Answer 29

Acid base extraction is used to change solubility in different solvents This enables the drug to be extracted and other components to be discarded

Question 30

Learning Objectives

Answer 30

Understand which functional groups are ionizable Understand ionization as a function of pH Make link between ionization and solubility correlate partitioning with ionization state