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)

. the presence of the salt in solution reduces the ability of the acid to ionize (common ion effect). Further. 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. very little conjugate base (Ac-) in solution comes from the acid.

.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.

pKb + log[Base]/[Salt] . [OH-] = Kb [Base] / [Salt] And using the relation ship [OH-] = Kw/ [H3O+] pH = pkw .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. pKw is affected by change in temp.

Activity coefficient and Buffer eqn. . 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.is one.

2 we can say log γAc = − − 0. For an oC. A= factor that depends on temp and dielectric constant of medium .1 or 0. having ionic strength not greater than 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.Activity coefficient and Buffer aq solution of univalent ion at 25 eqn.5 µ ∴ pH = pKa + log − [acid ] 1 + µ n= stage of ionisation.

: pH of acetate buffer increase with rise in temp. The pH of basic buffer more markedly . Temp. +ve value of dilution :pH rises with dilution -ve value :pH falls with dilution. pH of boric acidsodium borate buffer decrease with temp.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.

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. .

It is the ratio of the increment of strong acid or base to the small changes in pH brought about by addition.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. buffer index. β = Δ B/ ΔpH where Δ B is small increment in gram equivalent / liter of .

1 m NaAc in 1 liter of solution.01)=4. HAc + (0.01 m NaOH is added.10.1 m HAc and 0.01) 1) pH = pKa + log([salt]+[Base]/ [acid][Base]) Before addition pH= 4.76 + log (0.01) NaOH NaAc + H2O (0. To this 0.0 (0.77 The buffer capacity changes as log .Calculation of Buffer Capacity Consider acetate buffer containing 0.10.1+0.1+0.01/ 0.

Calculation of Buffer Capacity More exact eqn to calculate the buffer capacity (koppel and spiro eqn) β = 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. .

1+0.1 m HAc and 0. Consider acetate buffer containing 0.10.77 .76 + log (0.Influence of conc on Buffer capacity  The buffer capacity is also influenced by an increase in total conc of buffer constituents. To this 0. pH= 4.01 m NaOH is added.01)=4.1 m NaAc in 1 liter of solution.01/ 0.

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

=2H20 + Na+ + Cl- .Neutralization curves and buffer capacity Consider a titration curves of strong acid and weak acids when they 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.

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. The reaction between weak acid and strong base is incomplete bcz AcThe .= 2 H20 reaction between strong acid and strong base proceeds to completion.

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

303 [OH-] The total buffer capacity of water solution of a strong acid or base at any pH is sum of the separate capacities. . Or β = 2.303 [H3O+] The buffer capacity of a solution of strong base is similarly proportional to the hydroxyl ion conc. β = 2.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.

BUFFERS IN PHARMACEUTICAL AND BIOLOGICN SYSTEM .

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

1 + log ( [HCO3-]/[H2CO3] ) Where [H2CO3] represents the conc of CO2 present as H2CO3 dissolved in blood.1= 1.1. the buffer eqn for the carbonic acid and bicarbonate buffer of the blood is pH= 6.3 The lacrimal fluid or tears have a good .4-6.IN VIVO BIOLOGIC BUFFER SYSTEM  The dissociation exponent pK1 for the first ionization stage of carbonic acid in the plasma at body temp. and ionic strength of 0.16 is about 6. The ratio of bicarbonate to carbonic acid in normal blood plasma is log ( [HCO3-]/[H2CO3] ) = 7.

hydrogen ions are excreted by the kidneys.5 to 7. .0 with the range of 4.8 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.

Sorenson proposed mixture of salt of sodium phosphate for buffer of pH 6 to 8. 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 . Sodium chloride is added to maintain isotonicity.Pharmaceutical Buffers Buffer solutions are used in formulations of ophthalmic solutions.

H3BO3. 1.8 to 8 5. 5. The mix and their ph ranges are: 1. HCl and KHP.Pharmaceutical Buffers The buffers of clark and Lubs were determined at 20 o C and redetermined at 25 o C. 2. and KCl. 4. Below pH 2 HCl alone has considerable buffer efficiency and KCl is neutral salt .0 3. to 4.8 4. 2.2. NaOH.2. 8 to 10. NaOH and KH2PO4.2 to 2. NaOH and KHP. HCl and KCl.2 to 5.

05 to 0.5M is usually sufficient and buffer capacity of 0. The buffer eqn is satisfactory for approximate calculation within the pH range of 4 to 10.01 to . Calculate the ratio of salt and weak acid required to obtain the desired pH. A conc 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. Consider the individual concentration of the buffer salt and acid needed to obtain a suitable buffer capacity.Preparations Steps to develop a new buffer solution.

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

When the electrolyte conc is high. the pH calculated by use of the buffer eqn is somewhat different from the experimental value. . It is to be expected when activity coefficient are not taken in to account.Preparations Steps to develop a new buffer solution.

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

2 % NaCl = cells swells Buffered isotonic solutions . isotonic NaCl solutions. Mix small quantity of blood with aq. E. Isotonic solutions cause no swelling or contraction.g.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. 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.

alcohol.  The molecules of boric acid pass freely through the erythrocyte membrane regardless of conc.0 % boric acid solution is isosmotic to blood cell.  As a result boric acid solution is hypotonic and cause hemolysis. urea. ammonium chloride. The RBC membrane permit the passage of water molecules. Buffered isotonic solutions .  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. boric acid.  A 2.

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

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. This temp corresponds to the freezing point of 0.52 oC. The freezing point of blood is -0. . Now for both it is -0.56 oC and of tear is -0.80 oC.9% Nacl solutions.

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. ΔTf= Kfc. The sp value of L is written as Liso . New factor L=iKf is introduced to overcome difficulty. 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.

90 % (0.52 o C is Liso = ΔTf/c = 0. Liso is nearly equal to Kf value.Calculating Tonicity using Liso values  The Liso value for a 0.4 For dilute solutions of non electrolytes. which has freezing point depression of 0.154 M) solutions of NaCl.52/0. .154 = 3.

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

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 0.52-0.44 (0.Cryoscopic Method The freezing point depression of number of drugs is determined theoretically and experimentally.52 oC is isotonic 1 % solutions of apomorphine HCl have freezing point lowering value 0.08) .08 oC (std) Additional Nacl is added to reduce freezing point lowering value by an additional 0.

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

the conc c= 1g / M.NaCl / Tonicic equivalent method The NaCl equivalent (E) is amount of NaCl that is equivalent to 1 g of drug. ΔTf = 3. E value can be calculated from Liso value or freezing point depression of the drug.4 * E/58. for solutions containing 1g of drug in 1000 ml of solution.W And ΔTf = Liso *c = Liso 1 g/ M.45  .W now E is the wt For NaCl with same freezing point depression as 1 g of the drug.

0.9 % .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 .

How to make 30 ml of 1% solution of procaine HCl isotonic with body fluid.3 g of drug. The wt of the drug w.3g*0. . The preparation is then brought to its final vol with isotonic or buffered isotonic dilution solution.White –Vincet Method water is added to the drug in sufficient amount to form isotonic s0lution.21( W*E) = 0. is multiplied by the NaCl equivalent. E : 0.063g This is the quantity of NaCl osmotically equivalent to 0.

3 * 0.White –Vincet Method For 0.21 * 111. For the problem V = 0. enough isotonic NaCl solution or an isotonic buffered diluting solution is added to make 30 ml of finished pdt.0 To complete the isotonic solution. .0 ml The value of the ratio 100/0.1 = 7.9 g NaCl 100 ml water required For 0.1 So the eqn V = W * E * 111.063 * 100/ 9 = 7.9 = 111.063 g NaCl V ml water required V = 0.1 Where V is vol in ml of isotonic solution that may be prepared by mixing the drug with water.

3 g drug with sufficient water for drugs commonly used in ophthalmic and parental preparations. Compute the vol V of isotonic solutions of 0. the quantity for 1 fluid ounce of 1% solution. .The Sprowls Method The eqn V = 0.1 could be used to construct a table of values of V when the wt of the drug w is fixed.3 g.21 * 111.3 * 0. Sprowls chose the wt of drug 0.

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