Pharmaceutics Exam 2: Buffer Solutions

Ions can conduct an ______ current, and so substances that form ions in solution are called _______

electrical, electrolytes

A _______ is a compound that ________ ionize when dissolved in water and exist solely as the neutral, uncharged species

non-electrolyte, does not

What are some examples of nonelectrolytes?

Ethanol, dextrose, and some steroids

Drug compounds that do not _______________ are considered to be nonelectrolytes

ionize under physiological conditions

What functional groups are non electrolytes/ do not ionize in aqueous solutions?

Alcohols and sugars
Ethers
Esters
Ketones
Aldehydes
Most Amides

A ___________ ionizes completely when it dissolves in water and exists _____ in the form of positive and negative ions.

strong electrolyte, solely

A __________ is ionizable but ionizes ______; a fraction of dissolved molecules remain unionized while other acquire a positive and negative charge.

Weak electrolyte, partially

What is an example of a strong electrolyte?

Sodium Chloride (NaCl)

What is an example of a weak electrolyte?

Acetic acid and ammonia

Charged and uncharged forms from weak electrolytes will be:

1. Absorbed and distributed differently
2. Will bind to receptors differently
3. may be metabolized and eliminated differently.

The _____ of drugs in drug products is important because it influences _________ and _________ of the drug product

Ionization
route of administration, self life

________ is an oral anti-inflammatory drug that provides a good example of the importance of ionization in drug design.

Indomethacin

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

ionized, unionized

For Indomethacin to pass through ______ it requires some molecules to be in the ____ form in the intestines

lipophilic cell barriers, unionized

Once indomethacin has reached its site of action, only the _______ form binds to the receptor.

ionized

Indomethacin utilizes both is ____ and _____ forms for different aspects of ADME (absorption, distribution, metabolism, and excretion).

ionized and unionized

Water is a remarkable solvent because it can behave as both a ____ and a ____

acid and a base

pH of body fluids range from

1-8

The pH ranges of the stomach range from

1-3

The pH ranges of intestinal fluids ranges from

6-7

The pH of blood is ____ which corresponds to a h+ of approximately ___ nM

7.4, 40

From a formulation perspective it is important to control pH of a product to?

1. minimize drug degradation
2. improve patient comfort and compliance
3. improve delivery

Dosage forms, particularly liquids may have pH values outside the ____ range

1-8 pH

When a strong acid is added to water, the hydrogen ion concentration in solution ___ and pH _____

increases, decreases

Strong acids and bases ionize _____ in water

completely

Although Strong acids and bases are often used in pharmaceutical products to adjust the pH of liquids, there are no _______ or _______ drugs.

strong acid, strong base

Many drugs are classified as ______ acids or bases

weak

The main difference between weak acids and bases and strong acids and bases is that weak acids and bases only _______ dissociate in water because of their ________ ability to donate or accept protons.

Partially, diminished

What two forms do weak acids exist in?

uncharged, unionized species and negatively charged ions

What two forms do weak bases exist in?

Uncharged, unionized species and positively charged ions

An acid and base can be represent by an equilibrium in which the two species differ only by a proton called a ______________

conjugate acid- base pair

The law of mass action decribes

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

The larger the value of ______ the more ____ dissociates to donate protons.

Ka, BH+

The _____ the Ka the stronger the conjugate acid BH+ is and the ______ the base B.

larger, weaker

What can be manipulated to make Ka larger?

smaller pKa

Weak acids (or conjugate acids of weak bases) with a large _____ have a _____ pKa

Ka, smaller

Weak acids with a small ____ have a ____ pKa

Ka, large

Does the pKa value itself tell us whether a drug is a weak acid or base?

No

The lower the pKa of a compound the ______ the acidic form of the conjugate acid-base pair

lower

A weak acid with a pKa of 3 is a ____ acid than a weak acid with a pKa of 4.

stronger

The higher the pKa of a compound the _____ the basic form of the conjugate acid-base pair.

stronger

A weak base of pKa 8 is a ______ base than a weak base of pKa 7.

stronger

Weak acids and base drugs are often available as their ____

salts

The weak acid drug naproxen is also available as its sodium salt, _____

sodium naproxen

The weak base drug clonidine is also available in its salt form, ______

clonidine hydrochloride

Salts are considered _______ because they dissociate completely

strong eletrolytes

Pharmaceutical companies often develop the _____ form of a drug rather than the original weak acid or base form

salt

Why is the salt form of a drug preferred?

1. salts can more readily be crystallized in stable, easy to manufacture crystals
2. the dissolve faster in aqueous solutions
3. more stable for storage
4. easier to handle during processing

Amines are ______ and _____ and have short shelf life as ______

volatile, unstable
solids

Stability and shelf life improve drastically if an amine is converted to the ___________

hydrochloride salt

Buffer solutions resist changes in ____ when small amounts of acid or base are added or when the solution is diluted.

pH

Buffer solutions contain any weak acid-weak base pair, but are usually a ___________________ pair.

conjugate acid- conjugate base pair

Buffer capacity is defined as?

the amount of acid or base that can be added to a given volume of the buffer solution before pH changes to an appreciable degree.

The ability of a buffer to maintain constant pH is know as its ___________

buffer capacity

A buffer system is most useful at a ___________ or close to its _____ because there are adequate concentrations of both the __________________ forms of the buffer to neutralize added acid or base

solution pH, pKa
conjugate acid and base forms

The most effective buffers contain the ___________ in ______ and________ amounts

acid and base, large, equal

The pH of body fluid can vary from _____ (pancreatic/stomach)

8-1

____ are the most important buffers in the body because their amino and carboxylic groups act as proton acceptors and donors as H+ ions are added and removed from the environment.

Proteins

When is the acetate buffer useful?

For an easily made buffer in the low to mid pH range (3.6-5.6)

For preparations ot be buffered between pH 6-8 __________ is a useful system.

Sorenson's Phosphate Buffer

Concentrated multipurpose buffer solution is desired in the _________ range (2.5-6.5) the _______ buffer can be used

low to mid pH, citrate