Buffer Solutions

ionization

the process by which a neutral molecule gains/loses a proton; acquires a charge

electrolytes

substances that form ions in a solution

nonelectrolyte

compound that does not ionize when dissolve in water; neutral, uncharged species

common examples of nonelectrolytes

ethanol, dextrose, some steroids

these functional groups do NOT ionize in aqueous solutions

Alcohols
Sugars
Ethers
Esters
Ketones
Aldehydes
Majority of amides

A _______ __________ ionizes completely when dissolved in water, and exists solely in the form of positive and negative ions in solution

strong electolyes

Examples of a strong electrolyte

NaCl, KCl, Li2CO3

A _______ ___________ is ionizable, but ionizes partially

Weak electrolyte

Examples of weak electrolytes

acetic acid, ammonia

What properties are affected by ionization/unionization

absorption
distribution
binding to receptor
metabolism
elimination

the _______ form of indomethacin dissolves more rapidly and to a greater extent than the ________ form

ionized; unionized

only the ________ form of indomethacin will bind to the receptor

ionized

B-L acid

donates proton

B-L base

takes proton

what is the most compound present to receive proton from acid, or provide proton to a base

water

amphoteric

can behave as either a base or acid

H3O+

hydronium ion; product when water acts as a base

OH

alcohol; product when acid acts as an acid

ionization product constant of water

Kw = [H+] [OH-]

The value of Kw at 25 C is ____

10^-14

pH value

expresses the acidity of a solution

the symbol p in pH is a(n)

operator that converts a number into its negative log

pH scale

0-14

neutral pH

7; concentration of H+ ions = concentration of OH- ions

acidic solution has a pH ____ ______

below 7

in an acidic solution, the concentration of ________ ions exceeds the concentration of ________ ions

hydrogen; hydroxide

basic solution has a pH ____ _____

above 7

in a basic solution, the concentration of ________ ions exceeds the concentration of ________ ions

hydroxide; hydrogen

pH range of bodily fluids

1-8

pH range of the stomach

1-3

pH range of intestinal fluids

6-7

pH of blood

7.4

blood pH corresponds to a [H+] of ~_____

40 nM

the blood [H+} can vary from ______ to _______ without serious metabolic consequences

37 nM; 43 nM

tissue pH rarely exceeds _____

8

pH range a drug is expected to encounter?

1-8

if a drug does NOT have a functional group that ionizes within physiological pH environments, it behaves as a(n) _________ and remains __________ over the entire range

nonelectrolyte; unionized

reasons it is important to control the pH of a product

to minimize drug degradation
to improve patient comfort and compliance
improve delivery

why are pharmaceutical liquids with a higher pH (than physiological range) required?

makes drug more soluble
maintains good stability
allows for adequate shelf life

Examples of strong acids

HCl, H2SO4

Strong acids ________ __________ in water and exist entirely in their _________ form

dissociate completely; ionized

Strong acids are ______ electrolytes

strong

when a strong acid is added to water, concentration of hydrogen ions _______ and the pH ________

increases; decreases

Example of strong base

NaOH

when a strong base is added to water, concentration of hydrogen ions _______ and the pH ________

decrease; increase

T/F: there are NO strong acid or strong base drugs

true

weak acids and bases ______ ________ in water

partially dissociate

does the pH of water increase or decrease when a weak acid is added?

decreases

weak acids exist in solution in two forms:

un-ionized species
negatively charged ions

weak bases exist in solution in two forms:

un-ionized species
positively charged ions

common weak acids:

carboxylic acids
sulfonic acids
phenols
thiols
imides

an acid and base that differ only by a proton is known as a(n) ______________________

conjugate acid-base pair

Ka

acid dissociation constant

which is the conjugate base of HA?

A-

which is the conjugate acid of base B?

BH+

what does the law of mass action describe?

the dissociation of a weak acid and of the conjugate acid of a weak base

what does the law of mass state?

at equillibrium, the product of concentrations on one side of the equation divided by the product concentrations on the other side of the equation, is a constant reguardless of individual concentrations

A ______ Ka means the acid favors giving up protons and dissociates extensively

large

The larger the Ka the ________ the acid, and the ________ its conjugate base

stronger; weaker

The larger the Ka the ________ the conjugate acid, and the ________ the base

stronger; weaker

pKa=

-logKa

higher pKa indicates a _______ acid or a ________ base

weaker; stronger

Naproxen is a ______ _______

weak acid

Clonidine is a ______ ________

weak base

How do you get the salt of a weak acid?

reacting it with a strong base (such as NaOH)

What kind of salt is made from a weak acid?

sodium salt

How do you get the salt of a weak base?

reacting it with a strong acid (such as HCl)

What kind of salt is made from a weak base?

hydrochloride salt

salts are ______ electrolytes

strong

Reasons drugs are often developed into the salt form.

more readily crystallized into stable, easy to manufacture crystals
dissolve faster in aqueous solutions
more stable in storage
easier to handle

Salts of amines are preferred over the _____ _______ form because…

weak base; many amines are volatile, unstable, have short shelf life as solids

Buffer solution

resists changes in its pH when small amounts of acid or base are added or when solution is diluted; contains both an acid and base (weak-weak or conjugate pair), which react with added OH- and H+, respectively

pH of acidic buffer solutions.

<7

Examples of acidic buffer solutions.

acetic acid and sodium acetate

if the acidic buffer has an equal amount of weak acid and salt, it will have a pH of ______. An example is _______

4.75; acetic acid

If additional H+ ions are added, the equilibrium shifts to the _____

left

If OH- ions are added, the equilibrium shifts to the _______

right

The concentration of ______ remains constant and thus ________ remains constant

H+; pH

pH of alkaline buffer solutions.

>7

Examples of alkaline buffer solutions.

ammonia and ammonium chloride

if the alkaline buffer has an equal amount of weak base and salt, it will have a pH of ______. An example is _______

9.25; ammonia

Buffer capacity

the ability of a buffer to maintain a constant pH; the amount of acid/base that can be added to a given volume of buffer solution before pH changes

Why is the pH of pharmaceutical formulations often controlled through buffers?

to minimize drug degradation
improve patient comfort/compliance
allow delivery of a sufficient drug dose

pH of pancreatic fluid

8

pH range of blood

7.35-7.45

pH range of cells

7-7.3

Proteins are the most important buffers in the body, because their _______ and ____________ groups act as proton acceptors or donors

amino; carboxylic acid

Th phosphate buffer system consists of _________ ____________ ions as the proton donor and ___________ ___________ ions as the proton acceptor

dihydrogen phosphate; hydrogen phosphate

_________ ___________ injection is often used to raise the pH of some parenteral preparations

sodium bicarbonate

__________ buffer is useful for low to mid pH range (3.6-5.6)

acetate

_______________ buffer is useful for pH 6-8

sorenson’s phosphate

__________ buffer is useful as a concentrated multipurpose buffer in the low to mid pH range (2.5-6.5)

citrate