buffers complete ppt

8/3/2019 Buffers Complete Ppt.

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BUFFERSBUFFERSPREPARED BY: MR. JITENDRA PATEL


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WHAT ARE BUFFERS?

A buffered solution is one thatresists changing pH when acid orbases is added.

A buffered solution contains aweak acid and its salt or a weakbase and its salt.The resistance to a change in pH

is known as buffer action.


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e common on e ec anBuffer equation for a Weak Acidand its SaltThe pH of buffer and change on pH

can be calculated by use of buffereqn.

When Na Ac is added to HAc thedissociation constant for the weakAcid

Ka = [H3O+][Ac-] / [HAc]=1.75* 10-5


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Buffer equation for a Weak Acidand its Salt

Lets consider a solution containing aweek acid, HA, and its salt, NaAc. Saltsare strong electrolytes, so NaAc willcompletely dissociate in solution:

NaAc(aq) Na+(aq) + Ac-(aq)

The weak acid exists in equilibrium withits ions:

HAc(aq) + H2O (l) H3O+(aq) + Ac-

(aq)


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The ionization constant for the

acid is given by :

Ka = [H3O+][Ac-] / [HAc]Since we are dealing with weak acids,

very little conjugate base (Ac-) insolution comes from the acid.

The acetate ion supplied by the saltincreases the [Ac-].

To reestablish the constant Ka the

hydrogen ion term [H3O+] decreasewith formation of HAc.

Further, the presence of the salt insolution reduces the ability of the acid

to ionize (common ion effect).


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Ka = [H3O+] [salt] / [acid]

log Ka = log [H3O+] + log [salt] log [acid]

-pKa= -pH + log [salt] log [acid]

The Henderson-Hasselbalchequation may be derived from this

expression:

pH = pKa + log([salt]o/ [acid]o)

Ka is dissociation exponent.


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Buffer equation for a Weakbases and its SaltBuffer soln are not ordinarily

prepared from weak base and theirsalt bcz of volatility and instability

of the base and bcz of thedependence of their pH on pKw.

pKw is affected by change in temp.

[OH-] = Kb [Base] / [Salt]And using the relation ship [OH-] =

Kw/ [H3O+]

pH = pkw - pKb + log[Base]/[Salt]


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c v y coe c en anBuffer eqn.In the equilibrium of weak acid we

can replace conc with activity.

But activity= molar conc * activitycoefficient

The activity coefficient of theundissociated acid YAc- is one.

HAcCHAc

OCHOHCAcAc

HAc

AcOHka

)()( 333+++

==

)()( 333

+++

==

CAcAc

CHAckOCHOHOH a

++= Acacid

saltpKapH log][

][log


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c v y coe c en anBuffer eqn.For an aq solution of univalent ion at 25

oC, having ionic strength not greaterthan 0.1 or 0.2 we can say

The general equation for buffers ofpolybasic acids is

n= stage of ionisation, A= factor thatdepends on temp and dielectric

constant of medium

+

+=

+

=

15.0

][][log

1

5.0log

acidsaltpKapH

Ac

+

+=

1

)12(

][

][log

nA

acid

saltpKapH


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s ubufferAddition of small amt of water causesmall +ve or ve deviation bcz it altersactivity coefficient and water itselfbehave as a weak acid or weak base.Dilution value is the change in pH on

diluting the buffer solution to one half

of its original strength.+ve value of dilution :pH rises with

dilution-ve value :pH falls with dilution.Temp. : pH of acetate buffer increase

with rise in temp, pH of boric acid-sodium borate buffer decrease withtemp.

The pH of basic buffer more markedly


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s ubufferSALT EFFECT:

Addition of neutral salt to dilutebuffer solution lower the pH bylowering the activity coefficint and

pH of basic increases.


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Buffer capacityThe magnitude of the resistance of

a buffer to changes is referred to asa buffer capacity .

Also known as a buffer efficiency,

buffer index, buffer value.It is the ratio of the increment of

strong acid or base to the small

changes in pH brought about byaddition.

= B/ pH where B is small

increment in gram equivalent / liter of

C l l ti f B ff


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Calculation of BufferCapacity

Consider acetate buffer containing 0.1m HAc and 0.1 m NaAc in 1 liter ofsolution.To this 0.01 m NaOH is added.

HAc + NaOH NaAc + H2O

pH = pKa + log([salt]+[Base]/ [acid]-

[Base])Before additionpH= 4.76 + log (0.1+0.01/ 0.1-

0.01)=4.77The buffer capacity changes as log

(0.1-0.01)

(0.01) (0.1+0.01)


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Calculation of BufferCapacityMore exact eqn to calculate the

buffer capacity (koppel and spiroeqn)

= 2.3 C* Ka* [H3O+]/(Ka +[H3O+])2

Where C = total buffer conc that is

sum of the molar conc of the acid and

salt.


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Influence of conc on Buffercapacity

The buffer capacity is also influencedby an increase in total conc of bufferconstituents.

Consider acetate buffer containing0.1 m HAc and 0.1 m NaAc in 1 literof solution.

To this 0.01 m NaOH is added.

pH= 4.76 + log (0.1+0.01/ 0.1-0.01)=4.77


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Max Buffer Capacity

Koppel and Spiro eqn = 2.3 C* Ka* [H3O

+]/(Ka +[H3O+])2

The max buffer capacity occurswhen pH=pKa or when [H3O+] =Ka.

max = 2.3 C* [H3O+]2/(2[H3O

+])2

max = 2.3 C/4

max = 0.576 C

where C is total buffer concentration


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Neutralization curves andbuffer capacity

Consider a titration curves ofstrong acid and weak acids whenthey are mixed with increasing

quantity of alkali.The reaction of an equivalent of

acid with an equivalent of base is

called neutralization.The neutralization reactions are

written as

H3O+

(Cl-

) + (Na+

)OH-

=2H20 + Na+

+ Cl-


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The neutralization of strong acid bya strong base simply involves areaction between hydronium and

hydroxyl ionsH3O

+ + OH- = 2 H20

The reaction between strong acid and

strong base proceeds tocompletion.

The reaction between weak acid and

strong base is incomplete bczAc-


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Neutralization curves andbuffer capacityThe neutralization

of 10 ml of 0.1 NHCl and 10 ml of

0.1 N HAc by 0.1 NNaOH can beshown by plottingpH versus ml of

NaOH added.


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The buffer capacity of a solution ofstrong acid is shown by Van Slyke tobe directly proportional to thehydrogen ion conc. Or = 2.303 [H3O

+]

The buffer capacity of a solution of strongbase is similarly proportional to the hydroxyl

ion conc. = 2.303 [OH-]The total buffer capacity of water solution of

a strong acid or base at any pH is sum ofthe separate capacities.


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BUFFERS IN PHARMACEUTICAL

ANDBIOLOGICN SYSTEM

IN VIVO BIOLOGIC BUFFER


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IN VIVO BIOLOGIC BUFFERSYSTEMBlood is maintained at a pH of about

7.4 by primary buffers in plasma andsecondary buffers in the erythrocyte.The plasma contains carbonic acid/

bicarbonate and acid / alkali sodiumsalts of phosphoric acid as buffers.Plasma proteins, which behave as

acids in blood, can combine with

base and so act as buffer.In erythrocyte, the two buffer

system consist of

hemoglobin/oxyhemoglobin &



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IN VIVO BIOLOGIC BUFFERSYSTEMThe dissociation exponent pK1 for the

first ionization stage of carbonic acid inthe plasma at body temp. and ionicstrength of 0.16 is about 6.1. the buffereqn for the carbonic acid andbicarbonate buffer of the blood ispH= 6.1 + log ( [HCO3

-]/[H2CO3] )Where [H2CO3] represents the conc of

CO2 present as H2CO3 dissolved in

blood.The ratio of bicarbonate to carbonic

acid in normal blood plasma islog ( [HCO3

-]/[H2CO3] ) = 7.4-6.1= 1.3

The lacrimal fluid or tears have a good



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IN VIVO BIOLOGIC BUFFERSYSTEMUrine :

The urine of a normal adult has a pHof about 6.0 with the range of 4.5 to7.8

When the pH of the urine is belownormal values, hydrogen ions areexcreted by the kidneys.


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PreparationsSteps to develop a new buffer

solution.Select a weak acid having a pKa near to

a pH at which the buffer is to be used toensure a max buffer capacity.

Calculate the ratio of salt and weak acidrequired to obtain the desired pH. Thebuffer eqn is satisfactory forapproximate calculation within the pHrange of 4 to 10.Consider the individual concentration of

the buffer salt and acid needed toobtain a suitable buffer capacity.A conc of 0.05 to 0.5M is usually

sufficient and buffer capacity of 0.01 to


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Preparations

Steps to develop a new buffer

solution.Availability of chemicals, sterility of

the final solution, stabilty of the drug

and buffer on aging, cost ofmaterials, and freedom from toxicityshould be considered.

E.g. a borate buffer, bcz of its toxiceffects, certainly can not be usedstabilize a solution to be

administered orally or parenterally.


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Preparations

Steps to develop a new buffer

solution.When the electrolyte conc is high,

the pH calculated by use of the

buffer eqn is somewhat differentfrom the experimental value.

It is to be expected when activity

coefficient are not taken in toaccount.


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pH and SolubilityAt low pH the base is in the ionic

form, which is usualy very soluble inaqueous media.

As the pH is raised more

undissociated base is formed.When the amount of base exceeds

the limited water solubility of this

form, free base precipitates from thesolution.

So the solution should be buffered at

sufficiently low pH.


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Buffered isotonic solutionsPharmaceutical solutions that are

meant for application to delicate

membrane of the body should beadjusted to same osmotic pressure asthat of body fluids.Isotonic solutions cause no swelling or

contraction. E.g. isotonic NaCl solutions.Mix small quantity of blood with aq.

NaCl solutions of varying tonicity.Blood cells + 0.9 % NaCl = cells retain

normal size (Isotonic with blood)Blood cells + 2 % NaCl = cells shrink

and become wrinkled or crenated(Hypertonic with blood)

Blood cells + 0.2 % NaCl = cells swells


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Buffered isotonic solutionsThe RBC membrane permit the passage of

water molecules, urea, ammonium chloride,

alcohol, boric acid.A 2.0 % boric acid solution is isosmotic to

blood cell.The molecules of boric acid pass freely

through the erythrocyte membraneregardless of conc.

As a result boric acid solution is hypotonicand cause hemolysis.

So the solution containing quantity of drugcalculated to be isosmotic with blood isisotonic only when blood cells areimpermeable to solute molecules and

permeable to solvent molecules.

f i i


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Measurement of TonicityTwo methods

1. Hemolytic method2. Based on Methods used to

determine colligative properties.

l i h d


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Hemolytic methodSuspend the RBC in solutions.

Observe the effect of varioussolution of drug on appearance ofRBC.

Hypotonic solutions liberateoxyhemoglobin in direct proportionto the number of cells hemolysed.

By such means the vant Hoff i(=iRTC) can be determined and thevalue compared with that computedfrom cryoscopic data, osmotic co-efficient, and activit co-efficient.


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determine colligativepropertiesThis method is based on themeasurement of slight tempdifferences in the vapor pressure ofthermally insulated samples

contained in constant humiditychambers.

The freezing point of blood is -0.56

oC and of tear is -0.80 oC.Now for both it is -0.52 oC.

This temp corresponds to the

freezing point of 0.9% Nacl solutions,

a cu a ng on c y us ng i


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a cu a ng on c y us ng isovaluesFreezing point depressions for solutions of

electrolytes of both the weak and strong type aregreater than those calculated from eqn.Tf= Kfc,

New factor L=iKf is introduced to overcome

difficulty.Tf = Lc

The L value can be obtained from the

freezing point lowering of solutions ofrepresentative compounds of a given ionic

type at conc c that is isptonic with body fluids.

The sp value of L is written as Liso

a cu a ng on c y us ng i


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a cu a ng on c y us ng isovaluesThe Liso value for a 0.90 % (0.154 M)

solutions of NaCl, which has freezingpoint depression of 0.52 o C is

Liso =Tf/c = 0.52/0.154 = 3.4

For dilute solutions of non electrolytes, Lisois nearly equal to Kf value.

Methods for adjustingfor adjusting


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Methods for adjustingfor adjustingTonicity & pHTonicity & pHTwo type

1. Class I methods :NaCl or another substance is

added to the solution of the drug to lower the

freezing point of solution to -0.52 oC and thus

make isotonic with body fluid.E.g. Cryoscopic Method

NaCl equivalent method

2. Class II methods: water is added to the drug insufficient amount to form isotonic s0lution. The

preparation is then brought to its final vol with

isotonic or buffered isotonic dilution solution.

E. . White Vincet method and S rows


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Cryoscopic MethodThe freezing point depression of number of drugs

is determined theoretically and experimentally.How much NaCl is required to render 100 ml of

1% solutions of apomorphine HCl isotonic with

blood serum.Solutions having freezing point lowering value

0.52 oC is isotonic

1 % solutions of apomorphine HCl have freezingpoint lowering value 0.08 oC (std)

Additional Nacl is added to reduce freezing point

lowering value by an additional 0.44 (0.52-0.08)


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Cryoscopic MethodFor 0.58 freezing point lowering 1 % Nacl required

(std)So 0.44 freezing point lowering x % Nacl required

0.44* 1% = 0.58 * X

X = 0.76 %The solution is prepared by dissolving 1.0 g of

drug and 0.76 g of NaCl in sufficient amt of water

to make 100 ml of solutions


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NaCl / Tonicic equivalent methodNaCl / Tonicic equivalent methodMultiply the quantity of each drug with its NaCl

equivalent and subtract the value from the conc ofNaCl that is isotonic with body fluids , 0.9 %

hi i h d


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White Vincet Methodwater is added to the drug in sufficient amount to

form isotonic s0lution.The preparation is then brought to its final vol with

isotonic or buffered isotonic dilution solution.

How to make 30 ml of 1% solution of procaineHCl isotonic with body fluid.

The wt of the drug w, is multiplied by the NaCl

equivalent, E : 0.3g*0.21( W*E) = 0.063gThis is the quantity of NaCl osmotically equivalent

to 0.3 g of drug.


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Th S l M h d


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The Sprowls MethodThe eqn V = 0.3 * 0.21 * 111.1 could be used to

construct a table of values of V when the wt of thedrug w is fixed.

Sprowls chose the wt of drug 0.3 g, the quantity for

1 fluid ounce of 1% solution.Compute the vol V of isotonic solutions of 0.3 g

drug with sufficient water for drugs commonly

used in ophthalmic and parental preparations.


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buffers complete ppt

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