Pharmaceutics Buffer solutions

Ionization

A critical physicochemical property of a drug is

Ions

The charged species which are formed are called

Electrolytes

substances that form ions in solution are called

Electrical current

Ions conduct what?

Nonelectrolytes

compound that does not ionize when dissolved in water, and exists solely as the neutral, uncharged species

physiological conditions

Many drug compounds do not ionize under what conditions?

Nonelectrolytes

Many drug compounds are considered to be?

Alcohols and sugars Ethers

Esters

Ketones

Aldehydes

The majority of amides

These functional groups do not generally ionize in aqueous solution:

strong electrolyte

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

sodium chloride (NaCl)

An example of strong electrolyte

Na+ and Cl-

sodium chloride (NaCl) ionizes to form ___ and ___ in aqueous solution

acetic acid and ammonia

Simple examples of weak electrolytes are

influences route of administration and shelf life of the drug product

The ionization of drugs in the drug product is also important because it does what?

Rapidly, greater

The ionized form of the drug dissolves more ( slowly/ rapidly ) and to a ( greater/ smaller) extent than the un-ionized form.

Ionized form

Once indomethacin has reached its site of action, only the what form binds to the receptor?

The receptor

Once indomethacin has reached its site of action, only the ionized form binds to what?

ADME (absorption, distribution, metabolism, excretion) and pharmacodynamics of indomethacin

Both ionized and un-ionized forms are important for different aspects of what?

Bronsted–Lowry acids

compound that can donate a proton and a base is one that can accept a proton

it can behave as both an acid and a base

Water is a remarkable solvent because of what?

1 and 8

The pH of body fluids ranges between

1 and 3

The stomach is the most acidic region of the body with a pH that varies between

6 to 7

The normal pH of intestinal fluids is approximately

7.4

The pH of blood is

40 nM

When the pH of blood is 7.4, the [H+] is approximately

37 to 43

[H+] value can only vary from __ to __ nM without serious metabolic consequences.

composition and function of each tissue

Local pH in various tissues depends on what?

8

Local pH in various tissues rarely exceeds

1)To minimize drug degradation

2)To improve patient comfort and compliance

3) ...or to improve delivery.

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

1-8 pH range

Dosage forms may have pH values outside what range?

more soluble

Higher pH values of pharmaceutical liquids are often required to make the drug what?

Increase, decrease

when a strong acid is added to water, hydrogen ion concentration in solution _______ and pH ________

strong acid or strong base drug

Although strong acids and bases are often used in pharmaceutical products to adjust the pH of liquids, there are no what?

the uncharged, un-ionized species and negatively charged ions.

Weak acids exist in solution in which two forms?

a fraction

When a weak base is dissolved in water, only _______ of molecules accept protons.

Carboxylic acids, Sulfonic acids, Phenols, Thiols, Imides

Typical weak acids have the following functionalities:

conjugate acid–base pair

acid and base that can be represented by an equilibrium in which the two species differ only by a proton is called

Ka

is called the acid dissociation constant

HA

A simplified way of representing dissociation of any weak acid, denoted as

The law of mass action

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

Stronger

The larger the Ka, the _______ the acid HA

Weaker

The larger the Ka, the _______ its conjugate base A−

conjugate acid– base pair

Ka is a property of the what?

the strengths of both forms

Ka gives us information about what?

more, donate

The larger the value of Ka, the ____ BH+ dissociates to ______ proton

Stronger, weaker

the larger the Ka, the _____ the conjugate acid BH+ is, and the ______ the base B

small pKa

weak acids with a large Ka have what?

large pKa

weak acids with a small Ka have what?

pKa value

What does not tell us whether a drug is a weak acid or base?

a weak acid with a pKa of 4

a weak acid with a pKa of 3 is a stronger acid than ……

basic form of the conjugate acid–base pair

the higher the pKa of a compound, the stronger is the …..

a weak base of pKa 7

A weak base of pKa 8 is a stronger base than …….

their salts

Weak acid and base drugs are frequently available as what?

strong base such as NaOH

The salt of a weak acid is usually obtained by reacting it with what?

gives the sodium salt

What is given when the salt of a weak acid is usually obtained by reacting it with a strong base such as NaOH?

Salts and because they are strong electrolytes

What dissociate completely into their constituent ions in water and why?

Salts can be more readily crystallized into stable, easy to manufacture crystals

They dissolve faster in aqueous solutions, are more stable on storage, and are easier to handle during processing

Stability and shelf life improve dramatically if an amine is converted to the hydrochloride salt

Pharmaceutical companies often develop the salt form of a drug rather than the original weak acid or base form for what reasons?

salts of amine drugs

What is preferred over the weak base form?

Volatile, unstable, short

Many amines are _____ and _____, and have a _____ shelf life as solids.

buffered solution

one that resists changes in its pH when small amounts of acid or base are added, or when the solution is diluted

OH-, H+

Buffer solutions contain an acid to react with added ___ and a base to react with added ___.

conjugate acid–conjugate base pair

Buffer solutions are usually what type of acid-base pair?

The pH of the buffer

What depends on the pKa of the buffering substance and on the relative concentrations of conjugate acid and base?

the equilibrium shifts to the left

If additional hydrogen ions are added to this solution, they are consumed in the reaction with CH3COO− and the what happens?

remain constant

In the reaction with CH3COO−, the [H+] and thus the pH of the solution does what?

An alkaline buffer solution (pH >7)

This is commonly made from a weak base and one of its salts?

a solution of ammonia (pKa = 9.25) and ammonium chloride

What is an example of an alkaline buffer solution (pH >7)?

Buffer Capacity

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

buffer capacity

• What 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?

a solution pH at or close to its pKa

A buffer system is most useful as what?

because there are adequate concentrations of both the conjugate acid and base forms of the buffer to neutralize added acid or base

Why is a buffer system is most useful at a solution pH at or close to its pKa?

acid and base in large and equal amounts

The most effective buffers (with a large buffer capacity) contain what?

8, 1

The pH of body fluids can vary from __ in pancreatic fluid to __ in the stomach.

Proteins

What are the most important buffers in the body?

because their amino and carboxylic acid groups act as proton acceptors or donors as hydrogen ions are added or removed from the environment

Proteins are the most important buffers in the body, because of what?

phosphate buffer system

What is also important in maintaining pH of intracellular fluid?

3.6–5.6

Acetate Buffer is useful for an easily made buffer in the low- to mid-pH range of what?

6 and 8

For preparations to be buffered between pH __ and __ , Sorenson's Phosphate Buffer is a useful system

Citrate buffer

a concentrated multipurpose buffer solution is desired in the low- to mid-pH range (2.5–6.5), the ____ _____ can be used