EXAM2 L5 Flashcards

Drugs and Solubility

1
Q

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

A

Slide 26-28

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2
Q

If pH«pKa, solubility is nearly ______ of pH

A

independent

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3
Q

T/F: Solubility increases as pH decreases

A

False; solubility increases as pH increases

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4
Q

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

A

True; (diff. salts have different solubilities)

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5
Q

Crystalluria is

A

The formation of crystals in the urine

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6
Q

pH of urine

A

4.5-8

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7
Q

Ionized compounds are/are not reabsorbed in distal tubule?

A

Are not

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8
Q

Rate of clearance cant be impacted by urine pH due to

A

Variation in ionization state of drug

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9
Q

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

A

True

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10
Q

Enteric coating

A
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11
Q

A salt is formed by

A

Acid base reaction involving either proton donation or proton acceptance

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12
Q

Typical Pharmaceutical salts

A

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

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13
Q

What % of drugs are administered as salts?

A

50%

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14
Q

Salt formation modifies what properties of drugs?

A

Solubility, crystallinity, particle size, bulk, density

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15
Q

Common reasons for salt formation

A

Bioavailability
Developability
Purification
Intellectual property

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16
Q

Rule of thumb of salt formation

A

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

17
Q

Different Salts may ne used for different formulations ex.

A

Capsule
Injection
Suspension
Acid
Na
Mg

18
Q

Region 1 Solid Phase: Free Acid characteristics

A

Solubility depends on properties of acid

19
Q

Region 2: Solid phase salt Characteristics

A

Solubility depends on properties of salt

20
Q

Hydrophilic compounds have positive/negative log P values

A

Negative (Hydrophobic has Positive Log P)

21
Q

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

A

True

22
Q

pH Partition Hypothesis parts

A

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

23
Q

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

A

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

24
Q

Ion trapping in the stomach can lead to

A

Gastric mucosal cell damage (i.e. aspirin)

25
Q

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

A

True

26
Q

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

A

True

27
Q

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

A

True

28
Q

Limitations of pH-partition hypothesis

A

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

29
Q

Extraction Process

A

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

30
Q

Learning Objectives

A

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