ceutics - buffer solutions e2

ionization

the process by which a neutral molecule gains or loses a proton and thereby acquires a positive or negative electrical charge

ions

charged species that forms during ionization

electrolytes

substances that form ion in solution

nonelectroyte

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

physiological conditions

Most drug compounds that do not ionize under what are nonelectrolyte

alcohols, esters, ethers, aldehydes, ketones, amides

structure of some common non electrolyte functional groups

strong electrolyte

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

NaCl

what is an example of a strong electrolyte

weak electrolyte

ionizable but ionizes partially, a fraction of dissolved molecules remain un-ionized, while others acquire a positive or negative charge

acetic acid and ammonia

simple examples of weak electrolytes

absorbed and distributed differently, will bind to receptors differently, and may be metabolized and eliminate differently

What are the differences between charged and uncharged forms?

behavior

The ionization of a drug determines its what in the body?

influencing route of administration and shelf life

What two reasons is ionization of a drug product is important?

Indeomethaicn

an oral anti-inflammatory drug, provides a good example of the importance of ionization in drug design

weak electroylyte

when orally administered indeomethaicn is a ?

ionized form, un-ionized form

the (ionized, un-ionized form) of the drug dissolves more rapidly and to a greater extent than the (ionized, un-ionized) form.

un-ionzied

indomethacin needs to cross the lipophilic cell barriers which requires it to be in what form?

ionized form

however when the indomethacin has reached the site of action on the what form binds to the receptor?

both ionized and un-ionized forms

for different aspects of ADME and pharmodynamics what form(s) are needed?

Bronsted-Lowry acid

is a compound that can donate a proton

Bronsted-Lowry base

is a compound that can accept a proton

water

What is the solvent and medium for all living compounds?

water

the reactant in many pharmaceutical reactions of interest

water

the critical factor in determining the configuration of proteins and other biological macromolecules that are important in drug action

acid and base

water is a remarkable solvent because it can behave as

ampholytes

compounds with the dual property to act as an acid and a base are amphoteric

dipole

What does water possess to give it the ability to accept or donate a positively charged proton?

dipole

2 electric charges pf equal magnitude but opposite sign, separated by a small distance

hydronium ion

what does water form when it accepts a proton in equilibrium?

Kw

ionization product constant of water, says the relationship of the product of protons and hydroxide ions in an aqueous solution is always constant

14

What is the value of Kw at 25 degrees C?

acidic

a solution pH below 7 means the solution is what and the concentration of hydrogen ions exceeds the concentration of hydroxide ions

basic or alkaline

if the concentration of hydroxide ions is greater than that of hydrogen ions, the solution is what and has a pH greater than 7?

1 - 8

the pH of body fluids ranges between

1 -3

the stomach is the most acidic region of the body with a pH of?

6 - 7

the pH of intestinal fluids is

7.4

the pH of blood is and the (H+) is 40nM.

37 - 43 nM

the value of [H+] can only vary between what without metabolic consequences

8

local pH in tissues depends on the composition and function of each tissue and rarely exceeds?

ionization in this pH range of great interest

a drug can be expected to encounter physiological environments that vary between pH 1 and 8 which makes?

nonelectrolyte

If a drug does not have a functional groups that ionizes in this pH region, it behaves as a what and remains un-ionized over the entire physiological pH range

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

from a formulation perspective, it is important to control pH of a product you need to do three things?

dosage forms of liquids

what may have pH values outside the pH range of 1-8?

high pH values of pharmaceutical liquids

often required to make the drug more soluble, or to maintain good stability and an adequate shelf life

HCL or H2SO4

strong acids that dissociate completely in water and exist entirely in their ionized form, making them strong electroytes

hydrogen ion concentration in solution increases and pH decreases

what happen when a strong acid is added to water?

because a strong acid completely dissociates

why does the molar concentration of H+ equal the molar concentration of acid added for a monoprotic acid and twice the molar concentration for a diprotic acid.?

ionized form

a strong base like NaOH dissociates completely in water and exists entirely in its what form?

concentration of H+ will decrease and the solution pH will increase

what happens when the base hydroxide ion, OH-, reacts with H+ in the water?

molar decrease in H+ concentration

what will be equal to the molar concentration of NaOH added?

no strong acid or strong base drug

Although strong acids and bases are often used in pharmaceutical products to adjust the pH of liquids?

weak acids or weak bases

many drugs can be classified as what

dissociate in water and donate or accept protons

like strong acids and bases, weak acids and weak bases also

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

What is the main difference between the weak acids and bases?

the unchanged, un-ionized species and negatively charged ions

what are the 2 forms weak acids exist in?

accept protons

When a weak base is dissolved in water only a fraction of molecules what?

the uncharged, un-ionized species and positively charged ions

what are the 2 forms that bases exist in?

carboxylic acids, suflonic acids, phenols, thiols, imides

what are the functional groups of weak acids?

conjugate acid-base pair

an acid and base that can be respresented by an equilibrium in which the 2 species differ only by a proton

Ka

acid dissociation constant

the proportion of a weak acid or weak base is un-ionized or ionized

because ions behave differently from uncharged molecules, we are interested in what?

law of mass

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

acid favors giving up protons and dissociates extensively

what does a large value of Ka mean?

stable and does not have a high propensity to accept protons

When the Ka has a large value this means the conjugate base is

weaker the conjugate base

the larger the Ka, the stronger the acid and the

Ka

is a property of the conjugate acid-base pair and gives us information about the strengths of both forms.

the more the conjugate acid dissociates to donate protons

the larger the Ka value

weaker the base

the larger the Ka the stronger the conjugate acid is and the

pKa gets smaller

As the Ka gets larger the

weak acids or conjugate acids of weak bases

What has a large Ka and a small pKa?

large pKa

Weak acids with a small Ka have a

does not

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

examine functional groups that are known to be acidic and basic or see the types of salts the compound forms

What are 2 ways to determine if it was a weak acid or weak base?

stronger the acidic form of the conjugate acid-base paur

the lower the pKa of a compound the

stronger the basic form of the conjugate acid-base pair

the higher the pKa of the a compound the

their salts

What are weak acid and base drugs frequently available as?

salt

What does the weak base obtain when it reacts with a strong base?

drug salts

What can be made by combining weak acids and weak bases?

salt names

What can give us information about whether a drug in its un-ionized form is a weak acid or base?

strong electrolytes

What are salts when they dissociate completely into their constituents ions in water?

weak acid or base

The ions generated do not remain completely ionized if one of the compounds of the salt is what?

salts

What can be readily crystallized into stable and easy to manufacture crystals?

pharmaceutical companies

Who often develops the salt form of a drug rather than the original weak acid or base form?

dissolve faster in aqueous solution and are more stable on storage and are easier to handle during processing

Why are salts used instead of the original form?

amine drugs

What salts are preferred over the weak base form?

because they are most stable and improve dramatically

Why is hydrochloride salt used over the amine?

pH of the aqueous solution in which it is dissolved in

the relative concentrations of the ionized and un-ionized forms depend not only on the pKa of the weak acid or base but also?

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 an added what and a base to react with an added what?

conjugate acid-conjugate base pair

This can be any weak acid-weak base pair but are usually

pKa and relative concentrations of conjugate acid and base

the pH of the buffer depends on the what of the buffering substance and what?

sodium salt

acidic buffer solutions are commonly made from a weak acid and one its its salts is often a?

shifting the left when shifted to the right with ions to maintain equilibrium

What ways is the [H+] and the pH of the solution constant?

alkaline buffer solution

pH>7 is commonly made from a weak base and one of its salts

buffer capacity

the ability of a buffer to maintain constant pH, 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

solution pH or close to pKa

When is a buffer solution most useful because on the adequate concentrations of both the conjugate acid and base forms of the buffer to neutralize added acid or base?

large and equal amounts

The most effective buffers contain what?

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?

phosphate buffer system

What is the most important in maintaining pH of intracellular fluid?

dihydrogen phosphate ions (H2PO4-) and hydrogen post ions (HPO42-)

what are the 2 ions in equilibrium in the phosphate buffer system?