Buffers - PDF

Buffers 1  Content Buffers: Definition, buffer action, Henderson-Hasselbalch equation for acidic and basic buffer, Buffer capacity, approximate buffer capacity, Van Slyke's equation for buffer capacity, maximum buffer capacity, Buffers in biologic systems, pharmac...

Buffers 1  Content Buffers: Definition, buffer action, Henderson-Hasselbalch equation for acidic and basic buffer, Buffer capacity, approximate buffer capacity, Van Slyke's equation for buffer capacity, maximum buffer capacity, Buffers in biologic systems, pharmaceutical buffers, preparation of pharmaceutical buffer solution, importance of buffer in pharmacy Isotonic solutions, definition of hypotonic, hypertonic solution, importance of tonicity. distinction between iso-osmotic and isotonic Methods of adjusting isotonicity; cryoscopic method, the sodium chloride equivalent, White-vincent method. 2  Buffers Buffer solutions are solutions of compounds or mixtures of compounds resist changes in their pH upon addition of small quantities of an acid or alkali. Most buffer solutions usually consist of a mixture of a weak acid and one of its salt or a weak base and one of its salt. Buffer Action: The ability of certain solutions to resist change in their pH upon addition of an acid or a base is known as buffer action. 3 Examples: A solution of sodium chloride in water, its pH value is 7. Addition of even 1ml of 1 N HCl solution to 1 liter of NaCl solution lowers its pH value from 7 to about 3. Similarly, the addition of even 1 ml of 1 N NaOH solution to 1 liter of NaCl solution raises its pH to about 11. Sodium chloride solution is therefore not a buffer. 4  A mixture of a weak acid (acetic acid ) and its salt (sodium acetate), Acetic acid is very slightly dissociated in solution while sodium acetate being a salt is almost completely dissociated. The mixture thus consists of CH3COOH molecules as well as CH3COO — and Na+ ions. *If a strong acid is added to the mixture, the H+ ions supplied by the acid are immediately taken up by CH3COO— ions to form the very slightly dissociated CH3COOH. H+ + CH3COO— → CH3COOH Thus H+ ions are neutralized by the acetate ions present in the mixture and there is very little change in the pH value of the mixture. 5 If a strong base is added, the OH— ions supplied by the base are neutralized by acetic acid present in the mixture and again there is a very little change in the pH of the solution. OH — + CH3COOH → CH3COO — + H2O 6  A mixture of a weak base (ammonium hydroxide) and its largely dissociated salt (ammonium chloride), the mixture contains un-dissociated NH4OH as well as NH4+ and Cl— ions. If a strong acid is added to this mixture, the H+ ions supplied by the acid are neutralized by the base NH4OH H+ + NH4OH H2O + NH4+ 7  If a strong base is added, the OH— ions are neutralized by NH4+ ions forming very slightly dissociated NH4OH. OH— + NH4+ NH4OH In both cases there is very little change in the pH. 8 The Buffer Equation: The pH of a buffer solution and the change in the pH upon addition of an acid or a base can be calculated based on the use of buffer equation which is an expression developed by considering the effect of a salt on the ionization of a weak acid or a weak base when the salt and the acid or base have an ion in common. 9 1- Buffer Equation for a Weak Acid and its Salt salt pH = pKa + log acid This is known as buffer equation or Henderson-Hasselbalch equation for a weak acid and its salt. The buffer equation is a useful expression used in the preparation of buffered pharmaceutical solutions. 10  When the pH of the medium is equal to the pKa of the acid, the drug exists 50% in the ionized form and 50% in the unionized form. The pKa is dependent on the concentration of acid, conjugate base and H+ The pH can be changed by adding or removing acidic or basic substance. 11 Example 1: Calculate the pH of a buffer solution containing Phenobarbital and sodium Phenobarbital if the molar concentration of Phenobarbital is 0.03M and that of sodium Phenobarbital is 0.02M. The pKa for Phenobarbital is 7.4. Solution: According to the Henderson-Hasselbalch equation, pH= 7.4 + log (0.02)/(0.03) = 7.2……Answer 12 Example 2: What is the molar ratio [salt]/ [acid] to prepare acetate buffer of pH 5.0 (pKa of acetic acid = 4.76 )? Solution: [ salt] 5 = 4.76 + log [acid ] [ salt] log = 5 − 4.76 = 0.24 [acid ] [ salt ] = anti log 0.24 = 1.72 [acid ] 13 2- Buffer Equation for a Weak base and its Salt: Buffer solutions are not ordinarily prepared from weak bases and their salts because of the volatility and instability of the bases and because of the dependence of their pH on pKw, which is often affected by temperature changes. Certain pharmaceutical solutions such as a solution of ephedrine base and ephedrine hydrochloride which are mixtures of weak bases and their salts are often encountered. 14 The buffer equation for solutions of weak base and their corresponding salts [base] pH = pKw − pKb + log [ salt] 15 Example: What is the pH of a solution containing 0.10 mole of ephedrine and 0.01 mole of ephedrine hydrochloride per liter of solution? The pKb of ephedrine is 4.64 Solution: pH = 14 - 4.64 + log[0.1]/[0.01] pH = 9.38 + log 10 = 10.36 16 Buffer capacity Buffer efficiency, buffer index , buffer value is a measure of the efficiency of a buffer in resisting changes in pH. Conventionally, the buffer capacity (β) is expressed as the amount of strong acid or base, in gram-equivalents, that must be added to 1 liter of the solution to change its pH by one unit. Calculate the buffer capacity as: = gram equivalent of strong acid/base to change pH of 1 liter of buffer solution = the pH change caused by the addition of strong acid/base in which delta, (has its usual meaning, a 17 definite change)  The buffer capacity of a solution has a value of 1 when the addition of 1 gram Eq of strong base (or acid) to 1 liter of the buffer solution results in a change of 1 pH unit. The significance of this index will be appreciated better when it is applied to the calculation of the capacity of a buffer solution. The equation calculates the approximate buffer capacity. 18  Van Slyke's Equation for Buffer Capacity: An exact equation has been derived by Van Slyke for the determination of buffer capacity as follows: Where, C is the total buffer concentration, i.e., the sum of the molar concentration of the acid and the salt. 19 Maximum Buffer Capacity: A buffer solution containing a weak acid and its salt has a maximum buffer capacity (β max) when the pH is equal to the pka value for the weak acid or in equivalent terms [H3O] equals Ka + 2 [H 3O ] 2.303  max = 2.303 C + 2 = C (2 [H 3O ]) 4 β max = 0.576 C In which C is the total buffer concentration. 20 Example: What is the maximum buffer capacity of an acetate buffer with a total concentration of 0.020 mole per liter? β max = 0.576 X 0.020 = 0.01152 or 0.012 21 The buffer capacity depends essentially on two factors: 1. Ratio of the salt to the acid or base. The buffer capacity is optimal when the ratio is 1:1; that is, when pH = pKa 2. Total buffer concentration. For example, it will take more acid or base to deplete a 0.5 M buffer than a 0.05 M buffer. 22 Buffers in Biological Systems: Blood is maintained at a pH of about 7.4 by the so- called primary buffers in the plasma and the secondary buffers in the erythrocytes. The plasma contains carbonic acid/bicarbonate and acid/alkali sodium salts of phosphoric acid as buffers. Plasma proteins, which behave as acids in blood, can combine with bases and do act as buffers. In the erythrocytes, the two buffer systems consist of hemoglobin/oxyhemoglobin and acid/alkali potassium salts of phosphoric acid. 23  Experimentally buffer capacity of blood was about 0.039 gram equivalents per liter/pH unit for whole blood of which 0.031 was contributed by the cells and 0.008 by the plasma. Usually when the pH of the blood goes below 7.0 or above 7.8, life in serious danger. The pH of the blood in diabetic coma is alleged to drop as low as about 6.8. 24  Pharmaceutical Buffers Sorensen proposed a mixture of the salts of sodium phosphate for buffer solution of pH 6 to 8. sodium chloride is added to each buffer mixture to make it isotonic with body fluids. Hind and Goyan suggested a buffer system consists of boric acid, sodium borate and sufficient sodium chloride to make the mixture isotonic. It is used in ophthalmic solution in the pH range of 7 to 9. 25 Preparation of Pharmaceutical Buffer Solution: Determine the optimal pH for the product Select a weak acid with a pKa near the desired pH. This will ensure maximum buffer capacity (must be nontoxic and physically/chemically compatible with other solution additives). Calculate the ratio of salt to acid required to produce the desired pH (Henderson-Hasselbalch equation). The buffer equation is satisfactory for approximate calculations within the pH range of 4-10. 26  Determine the desired buffer capacity of the product. Calculate the total buffer concentration required to produce this buffer capacity (Van Slyke equation). (A concentration of 0.05 M is usually sufficient and a buffer capacity of 0.01 to 0.1 is generally adequate. Determine the pH and the buffer capacity of the completed buffer solution by using a reliable pH meter or pH paper. (This may not always be practical, especially when small volume, sterile products are prepared.) 27  Influence of Buffer Capacity and pH on tissue Irritation: Solution to be applied to tissues or administered parenterally are liable to cause irritation if their pH is greatly removed from the normal pH of the relevant body fluid. Consequently, the pharmacist must consider this point when formulating ophthalmic solutions, parenteral products, and fluids to be applied to abraded surfaces. Of possible greater significance than the actual pH of the solution is its buffer capacity and the volume to be used in relation to the volume of body fluid with which the buffered solution will come in contact. The buffer capacity of the body fluid should also be considered. 28  Tissue irritation, due to large pH differences between the solution being administered and the physiologic environment in which it is used, will be minimal if: a. The lower the buffer capacity of the solution b. The smaller the volume used c. The larger the volume and buffer capacity of the physiologic fluid. 29  Drug Stability In aqueous solution instability may arise through the catalytic effect of acids or bases. Minimum hydrolytic decomposition of solution of cocaine occurs in the range of pH of 2 and 5. Solution of thiamine HCl may be sterilized by autoclaving without appreciable decomposition if the pH is below 5 above this thiamin HCl is unstable. The stability of many disperse systems and specially of certain emulsion is often pH dependent 30  Drug activity Mandelic acid, benzoic acid and salicylic acid have pronounced antibacterial activity in unionized form but have practically no such activity in ionized form accordingly these substances require an acid environment to function effectively as antibacterial agents. 31  Drug Absorption The degree of ionization and lipoid solubility of a drug are two important factors that determine rate of absorption of drugs from the gastrointestinal their passage through cellular membranes. When drugs are weak organic acids or bases and exist in a non-ionized form, they can dissolve in lipids. Because cellular membranes have a lipid-like nature, these drugs can easily pass through them 32  pH and solubility Extent of ionization of a weak acid or a weak base is dependent on the pKa of the molecule and the pH of the environment. The extent of ionization determines MANY important pharmaceutical properties of a drug. At low pH, a base is predominantly in the ionic form which is usually very soluble in aqueous media. 33