P. 1
Buffers Complete Ppt.

|Views: 5|Likes:

See more
See less

05/01/2012

pdf

text

original

# BUFFERS

PREPARED BY: MR. JITENDRA PATEL

WHAT ARE BUFFERS?
A

buffered solution is one that resists changing pH when acid or bases is added. A buffered solution contains a weak acid and its salt or a weak base and its salt. The resistance to a change in pH is known as buffer action.

The common ion effect and Buffer equation for a Weak Acid and its Salt
The

pH of buffer and change on pH can be calculated by use of buffer eqn. When Na Ac is added to HAc the dissociation constant for the weak Acid Ka = [H3O+][Ac-] / [HAc]=1.75* 10
-5

The common ion effect and Buffer equation for a Weak Acid and its Salt  Let’s consider a solution containing a
week acid, HA, and its salt, NaAc. Salts are strong electrolytes, so NaAc will completely dissociate in solution: NaAc(aq)

Na+(aq) + Ac-(aq)

The weak acid exists in equilibrium with its ions: (aq) H3O+(aq) + Ac-

HAc(aq) + H2O (l)

Further. very little conjugate base (Ac-) in solution comes from the acid. . the presence of the salt in solution reduces the ability of the acid to ionize (common ion effect). The acetate ion supplied by the salt increases the [Ac-]. To reestablish the constant Ka the hydrogen ion term [H3O+] decrease with formation of HAc.The ionization constant for the acid is given by : Ka = [H3O+][Ac-] / [HAc] Since we are dealing with weak acids.

Ka = [H3O+] [salt] / [acid]   log Ka = log [H3O+] + log [salt] – log [acid] -pKa= -pH + log [salt] – log [acid] The Henderson-Hasselbalch equation may be derived from this expression: pH = pKa + log([salt]o/ [acid]o) Ka is dissociation exponent. .

[OH-] = Kb [Base] / [Salt] And using the relation ship [OH-] = Kw/ [H3O+] pH = pkw .pKb + log[Base]/[Salt] . pKw is affected by change in temp.Buffer equation for a Weak bases and its Salt Buffer soln are not ordinarily prepared from weak base and their salt bcz of volatility and instability of the base and bcz of the dependence of their pH on pKw.

.Activity coefficient and Buffer eqn.is one. In + − − − + the equilibrium of weak acid we can replace conc with activity. + αH 3O αAc (γAc CAc ) × (γH 3O CH 3O ) ka = = αHAc γHAcCHAc But activity= molar conc * activity coefficientγH 3O +CH 3O + ) = k a CHAc − αH 3O + = ( − [ salt ] pH = pKa + log + log γAc − [acid ] (γAc CAc ) The activity coefficient of the undissociated acid YAc.

A= factor that depends on temp and dielectric constant of medium .Activity coefficient and Buffer aq solution of univalent ion at 25 eqn.2 we can say log γAc = − − 0.5 µ 1+ µ The general equation for buffers of polybasic acids is A(2n − 1) µ [ salt ] pH = pKa + log − [acid ] 1+ µ [ salt ] 0.5 µ ∴ pH = pKa + log − [acid ] 1 + µ n= stage of ionisation. having ionic strength not greater than 0.1 or 0. For an oC.

Temp. The pH of basic buffer more markedly .Factors influencing pH of buffer of small amt of water cause Addition small +ve or –ve deviation bcz it alters activity coefficient and water itself behave 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. pH of boric acidsodium borate buffer decrease with temp. : pH of acetate buffer increase with rise in temp. +ve value of dilution :pH rises with dilution -ve value :pH falls with dilution.

.Factors influencing pH of buffer SALT EFFECT: Addition of neutral salt to dilute buffer solution lower the pH by lowering the activity coefficint and pH of basic increases.

β = Δ B/ ΔpH where Δ B is small increment in gram equivalent / liter of . It is the ratio of the increment of strong acid or base to the small changes in pH brought about by addition. buffer index.Buffer capacity The magnitude of the resistance of a buffer to changes is referred to as a buffer capacity β. Also known as a buffer efficiency. buffer value.

76 + log (0.01 m NaOH is added.77 The buffer capacity changes as log .1 m NaAc in 1 liter of solution.1+0.01)=4.10.01) NaOH NaAc + H2O (0.01) 1) pH = pKa + log([salt]+[Base]/ [acid][Base]) Before addition pH= 4.Calculation of Buffer Capacity Consider acetate buffer containing 0.10.0 (0.01/ 0. To this 0.1+0.1 m HAc and 0. HAc + (0.

3 C* Ka* [H3O+]/(Ka +[H3O+])2 Where C = total buffer conc that is sum of the molar conc of the acid and salt.Calculation of Buffer Capacity More exact eqn to calculate the buffer capacity (koppel and spiro eqn) β = 2. .

To this 0.1 m HAc and 0. pH= 4.1 m NaAc in 1 liter of solution.77 .Influence of conc on Buffer capacity  The buffer capacity is also influenced by an increase in total conc of buffer constituents.10.01 m NaOH is added.1+0.01)=4.76 + log (0. Consider acetate buffer containing 0.01/ 0.

Max Buffer Capacity Koppel The and Spiro eqn β = 2.576 C where C is total buffer concentration . β max = 2.3 C/4 β max = 0.3 C* [H3O+]2/(2[H3O+])2 β max = 2.3 C* Ka* [H3O+]/(Ka +[H3O+])2 max buffer capacity occurs when pH=pKa or when [H3O+] = Ka.

The reaction of an equivalent of acid with an equivalent of base is called neutralization.Neutralization curves and buffer capacity Consider a titration curves of strong acid and weak acids when they are mixed with increasing quantity of alkali.=2H20 + Na+ + Cl- . The neutralization reactions are written as H3O+ (Cl-) + (Na+)OH.

Neutralization curves and buffer capacity The neutralization of strong acid by a strong base simply involves a reaction between hydronium and hydroxyl ions H3O+ + OH.= 2 H20 reaction between strong acid and strong base proceeds to completion. The reaction between weak acid and strong base is incomplete bcz AcThe .

1 N NaOH can be shown by plotting pH versus ml of NaOH added.1 N HCl and 10 ml of 0.1 N HAc by 0.Neutralization curves and buffer capacity The neutralization of 10 ml of 0. .

. Or β = 2.303 [OH-] The total buffer capacity of water solution of a strong acid or base at any pH is sum of the separate capacities.Neutralization curves and buffer capacity The buffer capacity of a solution of strong acid is shown by Van Slyke to be directly proportional to the hydrogen ion conc. β = 2.303 [H3O+] The buffer capacity of a solution of strong base is similarly proportional to the hydroxyl ion conc.

BUFFERS IN PHARMACEUTICAL AND BIOLOGICN SYSTEM .

In erythrocyte. the two buffer system consist of hemoglobin/oxyhemoglobin & . can combine with base and so act as buffer. The plasma contains carbonic acid/ bicarbonate and acid / alkali sodium salts of phosphoric acid as buffers.IN VIVO BIOLOGIC BUFFER SYSTEM Blood is maintained at a pH of about 7. which behave as acids in blood.4 by primary buffers in plasma and secondary buffers in the erythrocyte. Plasma proteins.

the buffer eqn for the carbonic acid and bicarbonate buffer of the blood is pH= 6.4-6.3 The lacrimal fluid or tears have a good .1 + log ( [HCO3-]/[H2CO3] ) Where [H2CO3] represents the conc of CO2 present as H2CO3 dissolved in blood.IN VIVO BIOLOGIC BUFFER SYSTEM  The dissociation exponent pK1 for the first ionization stage of carbonic acid in the plasma at body temp.1= 1.16 is about 6. and ionic strength of 0.1. The ratio of bicarbonate to carbonic acid in normal blood plasma is log ( [HCO3-]/[H2CO3] ) = 7.

.0 with the range of 4. hydrogen ions are excreted by the kidneys.5 to 7.8 When the pH of the urine is below normal values.IN VIVO BIOLOGIC BUFFER SYSTEM Urine : The urine of a normal adult has a pH of about 6.

Sodium chloride is added to maintain isotonicity.Pharmaceutical Buffers Buffer solutions are used in formulations of ophthalmic solutions. As per Gifford when we mix various proportions of boric acid and monohydrated sodium carbonate they yield buffer solutions with pH range 5 to 9. A buffer system suggested by Palitzsch . Sorenson proposed mixture of salt of sodium phosphate for buffer of pH 6 to 8.

2. NaOH and KHP. 2. Below pH 2 HCl alone has considerable buffer efficiency and KCl is neutral salt . 4. 8 to 10. 1. NaOH and KH2PO4.Pharmaceutical Buffers The buffers of clark and Lubs were determined at 20 o C and redetermined at 25 o C. H3BO3. to 4.2. The mix and their ph ranges are: 1. NaOH.8 to 8 5. HCl and KHP.2 to 2. HCl and KCl.8 4. and KCl. 5. 2.2 to 5.0 3.

Calculate the ratio of salt and weak acid required to obtain the desired pH.05 to 0. The buffer eqn is satisfactory for approximate calculation within the pH range of 4 to 10.01 to . A conc of 0.Preparations Steps to develop a new buffer solution. Consider the individual concentration of the buffer salt and acid needed to obtain a suitable buffer capacity.5M is usually sufficient and buffer capacity of 0. Select a weak acid having a pKa near to a pH at which the buffer is to be used to ensure a max buffer capacity.

sterility of the final solution. and freedom from toxicity should be considered. a borate buffer.Preparations Steps to develop a new buffer solution. bcz of its toxic effects. . E. stabilty of the drug and buffer on aging. certainly can not be used stabilize a solution to be administered orally or parenterally.g. cost of materials. Availability of chemicals.

It is to be expected when activity coefficient are not taken in to account. .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 different from the experimental value.

So the solution should be buffered at sufficiently low pH. . When the amount of base exceeds the limited water solubility of this form. free base precipitates from the solution. which is usualy very soluble in aqueous media.pH and Solubility At low pH the base is in the ionic form. As the pH is raised more undissociated base is formed.

g.2 % NaCl = cells swells Buffered isotonic solutions . Blood cells + 0. Mix small quantity of blood with aq.Pharmaceutical solutions that are meant for application to delicate membrane of the body should be adjusted to same osmotic pressure as that of body fluids.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. Isotonic solutions cause no swelling or contraction. NaCl solutions of varying tonicity. isotonic NaCl solutions. E.

 So the solution containing quantity of drug calculated to be isosmotic with blood is isotonic only when blood cells are impermeable to solute molecules and permeable to solvent molecules.  A 2. alcohol. Buffered isotonic solutions .  The molecules of boric acid pass freely through the erythrocyte membrane regardless of conc.0 % boric acid solution is isosmotic to blood cell. The RBC membrane permit the passage of water molecules.  As a result boric acid solution is hypotonic and cause hemolysis. boric acid. urea. ammonium chloride.

Based on Methods used to determine colligative properties.Measurement of Tonicity Two methods 1. . Hemolytic method 2.

Hypotonic solutions liberate oxyhemoglobin in direct proportion to the number of cells hemolysed. and activity co-efficient. Observe the effect of various solution of drug on appearance of RBC. osmotic coefficient. . By such means the van’t Hoff i (π=iRTC) can be determined and the value compared with that computed from cryoscopic data.Hemolytic method Suspend the RBC in solutions.

80 oC. This temp corresponds to the freezing point of 0. Now for both it is -0.52 oC.56 oC and of tear is -0. The freezing point of blood is -0.Based on Methods used to determine colligative properties This method is based on the measurement of slight temp differences in the vapor pressure of thermally insulated samples contained in constant humidity chambers.9% Nacl solutions. .

ΔTf = Lc The L value can be obtained from the freezing point lowering of solutions of representative compounds of a given ionic type at conc c that is isptonic with body fluids. The sp value of L is written as Liso . ΔTf= Kfc.Calculating Tonicity using Liso values  Freezing point depressions for solutions of electrolytes of both the weak and strong type are greater than those calculated from eqn. New factor L=iKf is introduced to overcome difficulty.

154 = 3.52 o C is Liso = ΔTf/c = 0. . which has freezing point depression of 0.Calculating Tonicity using Liso values  The Liso value for a 0.90 % (0. Liso is nearly equal to Kf value.154 M) solutions of NaCl.4 For dilute solutions of non electrolytes.52/0.

The preparation is then brought to its final vol with isotonic or buffered isotonic dilution solution. Cryoscopic Method  NaCl equivalent method 2.Methods for adjusting Tonicity & pH  Two type 1. E. Class I methods : NaCl or another substance is added to the solution of the drug to lower the freezing point of solution to -0. White Vincet method and Sprows .g.g. Class II methods: water is added to the drug in sufficient amount to form isotonic s0lution. E.52 oC and thus make isotonic with body fluid.

Solutions having freezing point lowering value 0.08) .52-0. How much NaCl is required to render 100 ml of 1% solutions of apomorphine HCl isotonic with blood serum.Cryoscopic Method The freezing point depression of number of drugs is determined theoretically and experimentally.08 oC (std) Additional Nacl is added to reduce freezing point lowering value by an additional 0.52 oC is isotonic 1 % solutions of apomorphine HCl have freezing point lowering value 0.44 (0.

58 freezing point lowering 1 % Nacl required (std) So 0.58 * X X = 0.0 g of drug and 0.44* 1% = 0.Cryoscopic Method For 0.76 % The solution is prepared by dissolving 1.76 g of NaCl in sufficient amt of water to make 100 ml of solutions .44 freezing point lowering x % Nacl required 0.

45  . the conc c= 1g / M. for solutions containing 1g of drug in 1000 ml of solution. E value can be calculated from Liso value or freezing point depression of the drug.NaCl / Tonicic equivalent method The NaCl equivalent (E) is amount of NaCl that is equivalent to 1 g of drug.W And ΔTf = Liso *c = Liso 1 g/ M.W now E is the wt For NaCl with same freezing point depression as 1 g of the drug. ΔTf = 3.4 * E/58.

9 % .NaCl / Tonicic equivalent method Multiply the quantity of each drug with its NaCl equivalent and subtract the value from the conc of NaCl that is isotonic with body fluids . 0.

E : 0. is multiplied by the NaCl equivalent. How to make 30 ml of 1% solution of procaine HCl isotonic with body fluid.063g This is the quantity of NaCl osmotically equivalent to 0. The wt of the drug w. .3 g of drug. The preparation is then brought to its final vol with isotonic or buffered isotonic dilution solution.3g*0.21( W*E) = 0.White –Vincet Method water is added to the drug in sufficient amount to form isotonic s0lution.

For the problem V = 0.063 * 100/ 9 = 7.1 Where V is vol in ml of isotonic solution that may be prepared by mixing the drug with water.1 = 7.0 To complete the isotonic solution.3 * 0.21 * 111. .0 ml The value of the ratio 100/0.White –Vincet Method For 0.9 = 111.1 So the eqn V = W * E * 111.063 g NaCl V ml water required V = 0.9 g NaCl 100 ml water required For 0. enough isotonic NaCl solution or an isotonic buffered diluting solution is added to make 30 ml of finished pdt.

Sprowls chose the wt of drug 0.The Sprowls Method The eqn V = 0.3 * 0. . Compute the vol V of isotonic solutions of 0.3 g drug with sufficient water for drugs commonly used in ophthalmic and parental preparations.1 could be used to construct a table of values of V when the wt of the drug w is fixed. the quantity for 1 fluid ounce of 1% solution.3 g.21 * 111.

78 97.44/-:1107 ...5. (      %0.9  %054190.0.72..78.. 1:/4790.304194 .

./:9.3041 94  O 039054190:7308-043472.700..3472.7090/-90 /308 O .''   &#\$\$% &730 O %0:73041.541. .:08 /7403438.8.-4:9  9907.

//0/942.3094 .4388941 -47....84:9438 85071147/0302.!.0:9.7-43...943841 459. .90147-:110741594 \$4/:2.98.70:80/31472:.84:943957.3/:80/147 459.90/84/:2 .74:85745479438 41-47.39.2.2.3/.3/2434/7... .384943./.72.9 -:1107889028:0890/-!.90../ 84/:2-47.90900/-:110784:943895 7.3094 \$47038435745480/29:70418.94184/:2 5485.47/08.:11078 O O O O O :110784:9438.

:11078 O O O O O O O O %0-:1107841.-0-:1107 011.438/07.3/!  94  .3/!   94    .430.72.  .94 %02.8.3/90757.8..  .89739 .9.!.70   ..03.3/:-8 070/0907230/ .//0/94 ./:899043.3/ 94 045 .3/ 830:97.  .0:9.9 4.3/8.3/70 /0907230/..7 .308..3/  94    .3/! 94   .

:.5...8:9./.3.7.9 O ..43.9438 \$905894/0.3/ -:1107...... 41 94 8:8:.5./:.3.43..90907.981./06:.:.90 .3/0.30-:110784:943 O \$00..2..94393 9057.3/. -:1107.390/0870/5 %0-:1107063 8 8.794.5..9 O .!705.55742.039.0397.94418.0..9434190 -:11078.941 94 80307.9./706:70/ 944-9.045./300/0/944-9. 30..9.8:11. ..9.9 .-0 -:1107..304194 O 438/07903/.90.947147.5.90-:1107894-0:80/94038:70.5..

475.3/-:1107.8 89079419013.045.7.70.98  . 84:943 89..94190 . O 0907230905.3.84:943 94-0.90-:1107-.703907.907.984:/-0.3/1700/421742 94.3349-0:80/89.0110./2389070/47.!705.-47.-94190/7:.3 .419894.30-:110784:943 O .438/070/ O   .9438 \$905894/0..3/-:110743 ....425090/-:11070/84:943:83..02.-0 520907 .-941.8 .5.079.-0.489412.

03394.039 .90/-:804190-:11070638 8420.:0 O 9894-0050.045.:.8 905 .9.9.30-:110784:943 O 039000.!705...703499.4011. .9/110703917429005072039.4:39 ..43..7.90/03.9438 \$905894/0...97490.

80/2470:3/884.80 814720/ O 0390.80 570.59.5.800.90817429084:943 O \$49084:94384:/-0-:11070/.24:3941-.9 8:11.00/890 290/..1472 .03945  O .90784:-941981472 1700-..80839043.90/-. O 890587.6:04:820/.3/\$4:-9 94590-. 8:8:.0784:-03.

39147 ./:890/948..3/ -0.0:9.08808. .6:.08709.943   84943.8 9.90/ 507943..08873.7020. 80 84943.703.9 44/.08 ..72.39941-44/9.9-44/ 44/.9.6 .33472. .304190-4/ 84:/-0.84:9438 O O O O O O !.. .9-44/ .84:9438.9 -44/ 44/.94394/0..3/-:789 -07.55.84:94389.4397.930244-3 54943.08  . 84:943841.:11070/84943.420730/47.73943.57088:70.. 84:9438 82.941-4/1:/8 84943.:803480347 ..08  .90202-7..2048249.

.08..:11070/84943. 9-44/884943...43.943  .041.0-47.0 %0240.3070.459./5..3/ 50720.84:9438 O O O O O O %0#202-7.2243:2.44 -47. ../84:943 884943.039240.88.439./  -47..39941/7:.:08 :.7.2..708:9-47..4:833419000897:080250720..3050729905.90202-7.3/..:0841-47.:. .90/ 94-0848249.907 240.:08 :70.4303 -44/.:80 02488 \$49084:943..-094 -47. 8....-09484.7/08841. 94-44/.47/0 .3/03.-09484:90240./84:943854943./84:9438./84:9438848249.881700974:90 07974.70250720..5705.336:.:08.

2094/ O  .9 %42094/8 O  0249.0.0574507908 O .9.80/43094/8:80/94/0907230 .4.8:70203941%43.

/.041# O 54943.9.3.9.08 02480/ O 8:.3/.3 -0/0907230/.748.:0.20.74:884:94341/7: 43.9. .3 9411 #% . 48249.9040244-3 3/70.550.0249.941.425..3/90.84:9438-07.957454794394903:2-0741..4 011.4 011.45.2094/ \$:8503/90#384:9438 O -807.70/9 9.039 O ...9.7.425:90/1742.039 ..3890.0900110.

78  4 O 4147-4998 4 O %89025.80/439020.80/43094/8:80/94 /0907230.0 574507908 O %82094/8-.8.54757088:70 419072.8:70203941 899025/110703.90/8..9.72..38:.30/3 .438/070/.4389.2508.890701470 .439.39:2/9.08390.4.47708543/89490170035439 41 .3/ 4190.2-078 O %017003543941-44/8 4.3/ .84:9438 ...1:/8 .84943.9-49-44/..

:0.0/944... 9.9.07.420 /11.  01.9079..97490841-49900...9:8384 ..3-04-9.3/89743950.30/17429017003 543940734184:943841705708039.947183974/:.:041879903.93%43..950...9885943.:08 O O O O O 70035439/05708843814784:943841 00...0343.70 70.:.:9 %1.43.9. %0.4254:3/841..:.39480.884 .9-4/1:/8 %085.0 .90/1742063 %11.

..9:8384 .93%43.8170035439/0570884341  48 O 84 %1...:..:08 %084 .    84:943841 . .:0147.

 ..

974908 84 8 30.:0 O ..706:.941.   O 47/:9084:94384134300.

9 5 O O O O O O %4950  .8 :943 %0 5705.//0/949084:9434190/7:9440790 1700354394184:94394 4.45./:893%43.039.06:.3/\$5748 .//0/9490/7:3 8:11.47-:11070/84943.24:3994147284943../:94384:943   90'3.7.49 84943..47.0392094/  .3/9:8 2.084943.9438903-74:9949813.08 .349078:-89.882094/8.9-4/1:/   748.9078.094/ .094/8 147.092094/.882094/8.3.

:0 4 89/ //943.//0/9470/:.. 84:943841.0170035439 4073..8.8706:70/94703/07 241 84:943841.017003 54394073..//943.    .3.9 -44/807:2 \$4:9438.748...094/ O O O O O %0170035439/05708843413:2-0741/7:8 8/0907230/904709..:0-.5424753084943...:0 4884943. 42:.54247530...3/05072039.45.31700354394073.

.3/ 41.3 41 /7:.45..907 942.0 24184:9438 . 706:70/ 89/ \$4 1700354394073.748.094/ O O O O O 47 1700354394073.38:11.706:70/       %084:94385705.039.70/-/884.2941.

..

3341/7:3 241 84:943 90.90/174284 .06:.43.98 06:...24:3941.06:.039  8.0399441/7: ....:047 170035439/057088434190/7: 14784:9438.%43.0392094/ O O O O O O O %0.....9..439.:0..3-0.:.

84 .  3/%184 .

2017003 5439/05708843.98.  34890947.84190/7: %1  .

  84.

   .

  .

 ..

%43. 06:.0392094/ ...

9-4/1:/8   .3/8:-97.039..%43. 06:. O :95906:...43..9.41 .990.399410.9884943.:0174290../7:998.

9-4/1:/ %094190/7: 82:950/-90. 06:.09094/ O O O O O .7.03994 41/7: .24:3994 147284943...0 24184:94341574.9438903-74:9949813.8 :943  %05705.//0/9490/7:38:11.039.47-:11070/84943.39941.30 84943./:943 84:943  4942.48249... 06:.9078..4 984943.90 '3.039        %88906:.

 2.'2.907706:70/ 47 .09094/ O O O O O O O O 47 .907706:70/ '   .90 '3.

94 ..:041907. 2 %0.

 -05705.   \$490063'    070'8.384943.907 4790574-02'      %4.0 2411380/5/9 .-:11070//:93 84:9438.84:9439.70/-2390/7:9.84:943 034:84943. .4250909084943.84:94347.4324184943.92.//0/942.

9.2.399 1471:/4:3.907147/7:8.7039.04184:943 O 425:9090.-041.%0\$5748094/ %0063'     .43897:.9438  O .039.42243 :80/3459..5705.4'4184943.:0841'039094190 /7:810/ O \$5748.7..4:/-0:80/94 .48090941/7:  906:.3/5.9.84:943841  /7:98:11.

scribd
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->