Ionization

What determines the extent of ionization of a weak acid/base?

the intrinsic acidity/basicity (pKa) of the molecule and the pH of the environment

AKA pKa and pH

What do weak acids do?

Donate H+

What do weak bases do?

Accept H+

Which is ionized and which isn’t?

HA- Unionized

A- - Ionized

Which is ionized and which isn’t?

B- Unionized

BH+ - Ionized

What does the Henderson-Hasselbalch equation show us?

It helps us to determine the impact of the solution/environment pH and the drug pKa on the degree of ionization.

pka=pH?

50 % ionized and 50 % non-ionized

How do we know if it is an acid?

There are acidic groups and or have Acid/-ium

How do we know if it is a base?

There are basic groups and or have -ide/-ate

What are some examples of non-ionizable groups?

How are Drug salts made?

When ionized drug and ionized counterion have an ionic interaction with one another and crystallize.

How can salts form?

Strong Acid + Strong base

Weak Acids + Strong Base

Weak Base + Strong Acid

What is the pH Partition Hypothesis?

For Ionizable drugs, absorbed dose is determined by extent of unionized form at a given pH. The more lipid soluble form of a drug can permeate the cell membrane.

How does pH effect absorption of Acidic drugs?

In acidic Environments:

H+ is HIGH

HA increases (nonionized form)

Drug Absorption INCREASES

LIKE DISSOLVES LIKE!!!!!!!!!

In Basic environments:

H+ is LOW

A- increases (ionized form)

Drug Absorption DECREASES

How does pH effect absorption of Basic drugs?

In acidic Environments:

H+ is HIGH

BH+ increases (ionized form)

Drug Absorption DECREASES

LIKE DISSOLVES LIKE!!!!!!!!!

In Basic environments:

H+ is LOW

B increases (nonionized form)

Drug Absorption INCREASES

LIKE DISSOLVES LIKE!!!!!!!!!

How does ionization affect solubility?

A drug in its ionic form is more readily soluble in Polar solvents compared to its un-ionized form. LIKE DISSOLVES LIKE!!!!!!!

The extent of drug ionization of a weak base or weak acid is dependent on the pH of the solution and the pKa of the drug.

Thus, the aqueous solubility will be affected by the pH of the solution and the pKa of the drug

Why do we need to drink an extra glass of water with sulfa drugs?

It is relatively insoluble and is mostly in unionized form in the kidneys and causes crystalluria leading to kidney damage.

What are some solutions to crystalluria?

Increasing urine flow by forced diuresis

Increasing urine pH by oral sodium bicarbonate

How does pH affect solubility?

In acidic pH:

Acids Increase the amount of non ionized form → DECREASES solubility

Bases increase the amount of ionized form → INCREASES solubility

In Basic pH:

Acids increase the amount of ionized form → INCREASES solubility

Bases increase the amount of nonionized form → DECREASES solubility

What is So?

Solubility of unionized form in the absence of ionized form

AKA Intrinsic Solubility

What is Si?

The solubility of the ionized form

What is our goal as pharmacists?

To avoid mixing potentially incompatible drugs

To avoid pH that may precipitate non-ionized forms

Incompatibilities of drugs:

Weak acid + Strong base =

Equal molar species and dissolution of salt form yields pH > 7.0 solution

Weak Base + Strong Acid =

Equal molar species and dissolution of salt form yields pH < 7.0 solution

Weak Acid + Weak Base =

"Can" form ionic complexes with low solubility resulting in precipitation