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

Weak electrolytes are ionizable but

ionizes partially; examples are acetic acid and ammonia

Charged and uncharged forms will be

• absorbed and distributed differently

• bind to receptors differently

• may metabolize and eliminate differently

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

To enter bloodstream it need to cross

lipophilic cell barriers and requires at least some molecules to be unionized form in intestines

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

Water molecule possesses a

dipole giving it the ability to accept or donate a positively charged proton

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

Higher pH values of liquids require

to make the drug more soluble and or maintain good stability and shelf life

Molar decrease in H+ concentration is equal to

molar concentration of NaOH added

Strong acids and bases are used in pharmaceutical product to

adjust pH of liquids

Main difference is weak acids and bases only

partially dissociated in water because of their ability to donate or accept protons

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

Weak acids have functionalities:

• carboxylic acids

• sulfonic acids

• phenols

• thiols

• imides

Reverse reaction is not favored because

conjugate base is stable and does not have high propensity to accept protons

Larger the Ka value =

more BH+ dissociates to donate protons

The stronger the acid BH+ and weaker conjugate base B =

larger the Ka

pKa value does not tell us

whether a drug is weak acid or base

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

Weak acid drug naproxen is available as

sodium salt , sodium naproxen

weak base drug clonidine is available as

clonidine hcl

Salts of weak acid is obtained by

reacting with strong base such as NaOH that gives it sodium salt

Salts of a weak base is obtained by reacting with a

strong acid such as HCL giving HCL salt

Salts are

strong electrolytes and dissociate completely but the ions generated do not remain completely ionized if one is a weak acid or base

Salts are easily manufacutre as

crystals

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

Ionized and unionized forms depend on

pKa of weak acid or base and pH of aqueous solution

Buffered solutions

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

Buffer solutions contain

an acid to react with added OH- and base to react with added H+

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

equilibrium shifts to left; H+ and pH remains constant

Acidic buffer solutions are made from

weak acid and one of its salts often sodium salt

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

Phosphate buffer system is important in

maintaining pH of intracellular fluid

For easily made buffer in low to mid pH

acetate buffer is useful

Sorenson Phosphate buffer is useful fo

pH between 6 - 8

Citrate Buffer is useful for

low to mid pH 2.5-6.5