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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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Neutralization curves andbuffer capacity
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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Neutralization curves andbuffer capacity
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 &
IN VIVO BIOLOGIC BUFFER
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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
IN VIVO BIOLOGIC BUFFER
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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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