Physical Pharmacy I 2nd Stage Past Paper 2024-2025 PDF

University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics Physical pharmacy I 2nd stage Buffer Solutions...

University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics Physical pharmacy I 2nd stage Buffer Solutions 2024-2025 Outlines & Objectives  Introduction  Buffer equation  Drugs as buffer  pH indicators  Buffer capacity  Buffer and biological system 2 buffer 1 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics Introduction  Buffers are compounds or mixtures of compounds that, by their presence in solution, resist the changes in pH upon the addition of small quantities of acids or alkali.  The resistance to a change in pH is known as buffer action.  While if a small amount of a strong acid or base, is added to water or NaCl solution, the pH is altered considerably (there is no buffer action). 3  A combination of a weak acid and its conjugate base (i.e., its salt) or a weak base and its conjugate acid acts as a buffer.  If 1 mL of a 0.1 N HCl solution is added to 100 mL of pure water, the pH is reduced from 7 to 3. no buffer action  If the strong acid is added to a 0.01 M solution containing equal quantities of acetic acid and sodium acetate, the pH is changed only 0.09 pH units because the base Ac− ties up the hydrogen ions according to the reaction  If a strong base, sodium hydroxide, is added to the buffer mixture, acetic acid neutralizes the hydroxyl ions as follows: buffer 2 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics The buffer equation 5 6 buffer 3 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics  The buffer equation is important in the preparation of buffered pharmaceutical solutions; it is satisfactory for calculations within the pH range of 4 to 10. buffer 4 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics The 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.  Pharmaceutical solutions—for example, a solution of ephedrine base and ephedrine hydrochloride —however, often contain combinations of weak bases and their salts.  as the buffer equation or the Henderson–Hasselbalch equation, for a weak acid and its salt: buffer 5 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics Factors affecting pH of buffer solutions - - - - - -- - - - - - - - -- - - -- - - -- - - -- The addition of water in moderate amounts, although not changing the pH, may cause a small positive or negative deviation because it alters activity coefficients and 'because water itself can act as a weak acid or base. Note: Dilution value: is the change in pH on diluting the buffer solution to one half of its original strength. 11 12 buffer 6 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics  Note/ These actions are often weak (only one definite pH range) to counteract the pH changes brought about by CO2 of the air and the bottle alkalinity, so the buffers must be added. It expected to 13 Drugs as Buffer  It is important to recognize that solutions of drugs that are weak electrolytes also manifest buffer action. E.G:  Salicylic acid  ephedrine buffer 7 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics Example 1  Salicylic acid solution in a soft glass bottle is influenced by the alkalinity of the glass.  It might be thought at first that the reaction would result in an appreciable increase in pH;  however, the sodium ions of the soft glass combine with the salicylate ions to form sodium salicylate. Thus, there arises a solution of salicylic acid and sodium salicylate—a buffer solution that resists the change in pH Example 2  a solution of ephedrine base manifests a natural buffer protection against reductions in pH.  Should hydrochloric acid be added to the solution, ephedrine hydrochloride is formed, and the buffer system of ephedrine plus ephedrine hydrochloride will resist large changes in pH until the ephedrine is depleted by reaction with the acid.  Therefore, a drug in solution may often act as its own buffer over a definite pH range. buffer 8 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics pH Indicators  Indicators may be considered as weak acids or weak bases that act like buffers and also exhibit color changes as their degree of dissociation varies with pH  For example, methyl red shows  its full alkaline color, yellow, at a pH of about 6  and its full acid color, red, at about pH 4. HIn is the un-ionized form of the indicator, which gives the acid color, and In− is the ionized form, which produces the basic color. KIn is referred to as the indicator constant.  If an acid is added to a solution of the indicator,  the hydrogen ion concentration term on the right-hand side of equation is increased, and the ionization is repressed by the common ion effect.  The indicator is then predominantly in the form of HIn, the acid color.  If base is added,  [H3O+] is reduced by reaction of the acid with the base, reaction proceeds to the right, yielding more ionized indicator In−, and the base color predominates.  Thus, the color of an indicator is a function of the pH of the solution. buffer 9 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics  The equilibrium expression (8-16) can be treated in a manner similar to that for a buffer consisting of a weak acid and its salt or conjugate base. Hence and because [HIn] represents the acid color of the indicator and the conjugate base [In−] represents the basic color, these terms can be replaced by the concentration expressions [Acid] and [Base]. The formula for pH as derived from equation (8-18) becomes Colorimetric methods for pH calculation  Applications:  Less expensive compared to other methods  Used for non color aqueous solution  Used for non aqueous solutions  Limitations:  Less accurate and less convenient.  They are acid or bases and if added to unbuffered solution causing significant change in pH. 20 buffer 10 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics Buffer capacity  Or buffer efficiency, buffer index or value, represents the magnitude of the resistance of a buffer to pH changes.  Or the ratio of the increment of strong base (or acid) to the small changes in pH brought about by this addition. Then, according to this equation, addition of one gram equivalent of strong base (or acid) to one liter of the buffer solution results in the change of one pH unit. How can you make an approximate calculation for buffer capacity?  For ex. Acetate buffer containing (0.1mole each of acetic acid and sodium acetate in one liter of solution) to which 0.01mole of NaOH is added  resulting in increase of salt conc. [Na+ Ac-] by (0.01 mole/liter), and [HAc] conc. decreases proportionally because each increment of base convert 0.01mole of acetic acid into 0.01mole of sodium acetate according to the following equation: And 22 buffer 11 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics Buffer capacity  the buffer capacity depends on:  (a) the value of the ratio [salt]/[acid], increasing as the ratio approaches unity  (b) the magnitude of the individual concentrations of the buffer components, the buffer becoming more efficient as the salt and acid concentrations are increased. 23 Neutralization curves and buffer capacity:  By considering the titration curves of strong and weak acids when they are mixed with increasing quantities of alkali, the reaction of an equivalent of an acid with an equivalent of the base called neutralization. buffer 12 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics Buffers in Pharma. & Biological systems  In vivo biologic buffer system:  Blood maintained the pH at 7.4 by so-called primary buffers in the plasma and the secondary buffers in the erythrocytes.  Plasma contains (carbonic acid/bicarbonate, acid/alkali salts of phosphoric acid and plasma proteins).  Erythrocytes contain two buffer systems (hemoglobin/oxy- hemoglobin and acid/alkali potassium salts of phosphoric acid).  It is usually life threatening for the pH of the blood to go below 6.9 or above 7.8, as in diabetic coma (pH as low as 6.8). Then, it is important for maintaining pH in a range of (7-7.8) 25  For urine, the 24-hr. urine collection of a normal adult have the pH averaging about 6 units, or it may be as low as 4.5 or as high as 7.8. - When the pH of urine is below normal value, hydrogen ions are excreted by kidney. Conversely when the pH is about 7.4, hydrogen ions are retained by the kidney action. 26 buffer 13 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics Pharmaceutical buffers:  Are used for:  Formulation of ophthalmic solutions  Colorimetric determination of pH  Research studies in which pH must be held constant 27  There are different types with different pH ranges containing mixtures of solutions (found in pharmacopeia) with or without isotonicity enhancer (like NaCl).  Mixtures of boric acid and monohydrated sodium bicarbonate at various proportions with pH range 5-9.  Mixtures of the salts of sodium phosphate, pH range 6-8.  Boric acid and sodium borate, range 7-9.  NaOH and KH2PO4 , range 5.8-8 28 buffer 14 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics Influence of buffer capacity and pH on tissue irritation:  Tissue irritation, due to large pH differences between the solution being administered and the physiologic environment in which it is used, will be minimal: A. the lower is the buffer capacity of the solution, B. the smaller is the volume used, for a given concentration, and C. the larger are the volume and buffer capacity of the physiologic fluid. 29 Buffer capacity and tissue irritation:  Eye irritation my be resulted from the presence of free form of a drug at the physiologic pH, it is more often due to the acidity of the eye solution.  Phosphate buffer can cause more irritation than boric acid buffer due to higher buffer capacity of Ph buffer.  Parenteral solution are usually not buffered or they are buffered to a low capacity so that, the buffer of the blood may readily bring them within the physiologic pH range.  For oral administration, like aspirin is absorbed more rapidly in system buffered at low buffer capacity than in system containing no buffer or in highly buffered preparations. Gastric irritation is also affected by buffer capacity. 30 buffer 15 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics Stability versus optimum therapeutic response:  Undissociated form of weakly acidic or basic drugs often has a higher therapeutic activity than the dissociated salt form (less lipophilic).  For ophthalmic drugs (weakly basic alkaloid, pilocarpine, pkb= 7.15), therapeutic response is increased as the pH of solution and hence the concentration of the undissociated base were increased.  At low pH about 4, ionic form predominates, so low penetration or slow.  Tears with pH about 7.4, the drug found mainly in free base form. 31 The solutions of drugs can be buffered at a low buffer capacity and at pH that is a compromise between that of optimum stability and the pH for maximum therapeutic action. 32 buffer 16 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics pH & Solubility  The influence of buffering on the solubility of an alkaloidal base: At a low pH, a base is predominantly in the ionic form, which is usually very soluble in aqueous 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 solution. Therefore, the solution should be buffered at a sufficiently low pH so that the concentration of alkaloidal base in equilibrium with its salt is calculated to be less than the solubility of the free base at the storage temperature. Stabilization against precipitation can thus be maintained. 33 Buffered Isotonic Solutions  Isotonic solutions cause no swelling or contraction of the tissues with which they come in contact, and produce no discomfort when instilled in the eye, nasal tract, blood, or other body tissues.  Hypertonic solution: ….. Shrink RBCs  Hypotonic solution: ……. Haemolysis 34 buffer 17 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics Methods of Adjusting Tonicity & pH Sodium Chloride Equivalent Method: 36 buffer 18 University of Basrah college of pharmacy - 11/06/1446 Department of Pharmaceutics Sodium Chloride Equivalent Method: 37 Thanks for your attention 38 buffer 19