Buffer Solutions

Ions

charged species that are formed

Electrolytes

can conduct electrical current so that substances form ions in solution

Nonelectrolyte

does not ionize when dissolved in water, exist as neutral and uncharged

Compounds that don’t ionize in aqueous solution

• Alcohols

• Ethers

• Esters

• Ketones

• Aldehydes

• Majority amides

Strong electrolyte

ionize completely when dissolve in water and exist solely in positive and negative ions

Ionization of drugs is important for

influencing route of administration and shelf life of product

What dissolves more rapidly and to greater extent

Ionized form of drug

Once indomethacin has reached its site of action

only ionized form binds to receptor

Both ionized and unionized forms are important for

ADME and pharmacodynamics of indomethacin

What is a remarkable solvent and behave in both acid and base

Water

pH in pharmaceutical systems

• Body fluids: 1-8

• Stomach: 1-3

• Intestinal fluid: 6-7

• Blood: 7.4

How to control pH of a product

• minimize drug degradation

• improve patient comfort and compliance

• improve delivery

Who has pH values outside the 1-8 range

Dosage forms such as liquids, solutions, suspensions

Strong acids and bases are used in pharmaceutical product to

adjust pH of liquids

Two forms of weak acids

• uncharged, unionized species

• negatively charged ions

Conjugate acid base pair

can be represented by equilibrium where they differ by a proton

Larger the Ka value =

more BH+ dissociates to donate protons

The stronger the acid BH+ and weaker base B =

larger the Ka

Weak acids with large Ka have

small pKa and vice versa

Weak acid with pKa of 3 is

stronger than a pKa of 4

Weak base of pKa 8 is

stronger than weak base pKa 7

Pharmaceutical companies develop salt form of drug rather than weak acid or base form because

• dissolve faster in aqueous solutions

• more stable

• easier to handle

• preferred over weak base form

Many amines are

volatile and unstable and have short shelf life

Buffered solutions

resist changes in pH when small amounts of acid or base are added; usually conjugate acid - conjugate base pair

If additional hydrogen ions are added to solutions of CH3COO- then

equilibrium shifts to left; H+ and pH remains constant

Alkaline buffer is made from

weak base and one of its salts

ex) ammonia and ammonium chloride

Buffer capacity

ability of buffer to maintain constant pH; amount of acid or base that can be added to give volume of buffer solution before pH changes

What is the most useful at solution pH because there ae adequate conc. of both conjugate acid and base

Buffer system

Most effective buffers contain

acid and base in large and equal amount

What are the most important buffers in body

Proteins; because amino and carboxylic acid groups act as proton acceptors or donors as hydrogen ions