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unit V pH, buffers and Isotonic solutions.pptx

PH Buffer B Pharm Syllabus

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pH, buffers and Isotonic solutions PS302: PHYSICAL PHARMACEUTICS - I B. Pharm. II Year I Sem By: Kabita Banik Assistant Professor Pharmaceutics.
Sorenson’s pH scale: pH refers to potential of hydrogen ions concentration. Sorenson’s has defined pH of a solution as the logarithm of the reciprocal of the hydrogen ions or hydronium ions concentration [H3O + ]. Mathematically pH= log 1/ [H3O + ] pH= log 1- log [H3O + ] (as the value of log 1 is Zero) pH= - log [H3O + ] Hence pH can also defined as the negative logarithm of hydrogen ion or hydronium ions concentration. The concentration of [H3O + ] is expressed in molarity, mol/L, etc. so according to Sorenson’s , The solutions having [H+ ] value greater than 10-7 are called acidic solution. The solutions having [H+ ] value less than 10-7 are called basic solution. Hence pH value of all acidic solutions are less than 7 and pH value of all basic solutions are greater than 7.
Sorenson developed a scale based on the pH value and different concentration of H3O + in a solution which is called Sorenson’s pH scale. Solvent is water Temperature is 25°C .
Sorenson’s scale (Table-1) assigns , a pH of 0 to 14, •0 being the most acidic, •14 being the most basic, and •7 being neutral (neither acidic nor basic). The pH scale works in powers of ten, so each jump in number is a multiple of ten in concentration. For example a pH of 1 is 10 times more acidic than a pH 2. The value 7 at which the hydrogen and hydroxyl ion concentrations are about equal at room temperature is referred to as the neutral point, or neutrality. The neutral pH at 0°C is 7.47, and at 100°C it is 6.15.
Applications: The pH of the solutions must be controlled in pharmacy particularly in formulations of eye drops, ear drops, injections and liquid orals for the following reasons. 1. Enhancing solubility and stability: The pH of the pharmaceutical preparations should be adjusted so as to make the API soluble and remain physically stable in the formulation. 2. Improving purity: The purity of the protein can be determined as the amphoteric compounds are least soluble at their isoelectric points. 3. Absorption of drugs: The drug molecules are absorbed differently from various parts of the GIT as the later differs in their pH. 4. Optimizing biological activity: Enzymes have maximum activity at a definite pH value. 5. Comforting the body: The pH of the formulations that are administered to different tissues of the body should be optimum to avoid irritation (eyes), haemolysis (blood) or burning sensation (abraded surface). 6. Storage of products: Special type of glass is used in case the glass container imparts alkalinity and alters the pH of the contents.
The pH indicators: •The pH indicator is a weak acid or weak base that exists in tautomeric form that readily interconvert. •It is a solution when added to test solution produces a colour change, which helps in determining the pH of the test solution. •The colour of any indicator depends on the pH of the solution. •Ex- Phenolpthalein, methyl red, Thymol blue etc. Universal indicator Universal indicator is defined as a mixture of several indicators, which gives different color shades as the pH of the solution varies, in a particular pH range.
Measurement of pH: The are two widely accepted methods for the determination of the pH of a solution (a) Colorimetric method (b) Electrometric method Colorimetric method: This method based on the principle of colour comparison of the test solution to that of the standard both treated with universal indicator. This method is used to determine the pH of the solution in the pH range of 3 to 11 ± 0.2 units. Commercially available indicator strips of filter papers are used for identifying the pH. Otherwise several standard solutions can be prepared or procured which are mixed solution of buffer and indicator. Also Capillators and Comparators are commercially available for this purpose.
Capillators: Standard solutions (mixture of buffer solution and universal indicator) of small volume placed in capillary tubes are called capillators. Comparators: Standard solutions (mixture of buffer solution and universal indicator) of large volume placed in capillary tubes are called comparators. This is useful in examining turbid and coloured solutions.
Method: Standard buffer solutions of known pH ranging from 3.0 to 11.0 are prepared with 1.0 pH interval A few drops of universal indicator solutions are added to the above solution that produce different colours. Similarly few drops of universal indicator are also added to the solution to be tested It produce a colour depending upon its pH The colour of the test solution is compared with the colour of the standard solutions..
Precautions: Standard solutions must be protected from light to avoid colour fading All tubes must have same dimension. i.e. tube diameter and thickness of glass. Advantages: Less expensive Acid-base reaction of non-aqueous solution can be studied. Easy estimation of pH unless the drug shows buffer action. Disadvantage: This method is less accurate and less convenient It is not useful for coloured or turbid solution. The indicators used may impart a deviation in pH to buffered solution. This is not useful in presence of salts, proteins etc.
Electrometric method Principle: The magnitude in the potential difference between glass and a solution containing hydrogen ion varies with concentration of H+ concentration. Hence the pH of the solutions are determined by means of the electrodes. Hydrogen electrode and glass electrodes are used for this purpose. However glass electrodes are commonly used. The instrument used to determine the pH of unknown solution by this method is called pH meter. Method: A pH metre with its control knobs are presented in fig.1. The glass electrode is attached to the instrument.
Method: Step-1: At first the instrument temperature is set to that of the solution temperature. Step-2: The electrode is immersed into a standard buffer solution of pH 7.0. The potential control knob is adjusted till the pH reading in digital meter becomes 7.0. Step-3: Then the instrument is calibrated using standard buffers of pH 4.0 (M/20 potassium hydrogen phthalate) or/and pH 9.14. Step-4: The electrode is now rinsed with distilled water properly and re-immersed into the test solution. The pH value is obtained from the digital meter. The pH of the test solution can be changed by the addition of slight amount acid or base solution (depending upon the desired direction of change) and the procedure is followed till the desired pH is obtained. Advantages: It gives an accurate measurement of pH. •Glass electrode is not affected by oxidation-reduction system. •The electrode establishes equilibrium rapidly. •The indicator need not required. •The pH range of measurement is large Disadvantages: The cost of pH meter is high compared to colorimetric method. This method is not suitable for viscous solutions and gels because of poor ionic mobility
Hydrogen-Electrode Method A hydrogen electrode is made by adding platinum black to platinum wire or a platinum plate. It is immersed in the test solution and an electric charge is applied to the solution and the solution is saturated with hydrogen gas. The electrode potential is measured between platinum black electrode and silver chloride electrode. This potential is inversely proportional to pH of the solution. The hydrogen-electrode method is a standard among the various methods for measuring pH. The values derived using other methods become trustworthy only when they match those measured using hydrogen electrode method. However, this method is not appropriate for daily use because of the effort and expense involved, with the inconvenience of handling hydrogen gas and great influence of highly oxidizing or reducing substances in the test solution.
Quinhydron-Electrode Method When quinhydrone is added to a solution, it separates into hydroquinone and quinone. Because quinone’s solubility varies depending on the pH value of the solution, pH can be determined from the voltage between a platinum and reference electrode. Although this method is simple, it is seldom used today, because it does not work when oxidizing or reducing substances are involved, or when the test solution has a pH above 8 or 9. Note: Quinhydron solution of a certain pH is sometimes used to check whether an ORP meter is operating normally. The principle of the quinhydron electrode is applied in such a case.
• A solution whose pH is not altered to any great extent by the addition of small quantities of either an acid or base is called buffer solution. • Buffer is also defined as the solution of reserve acidity or alkalinity which resists change of pH upon the addition of a small amount of acid or alkali. • Many chemical reactions are carried out at a constant pH. In nature, there are many systems that use buffering for pH regulation. For example, the bicarbonate buffering system is used to regulate the pH of blood, and bicarbonate also acts as a buffer in the ocean. What is Buffer
Types of buffer solutions • Acidic Buffer: It is formed by the mixture of weak acid and its salt with a strong base. Examples: (i) CH3COOH + CH3COONa, (ii) HCl + NaCl, (iii) Boric acid + Borax etc. • Basic Buffer:It is formed by the mixture of a weak base and its salt with strong acid. Examples: (i) NH4OH + NH4Cl, (ii) NH4OH + NH4NO3, (iii) Glycine + Glycine hydrochloride • Simple Buffer: It is formed by a mixture of acid salt and normal salt of a polybasic acid, Example: Na2HPO4 + Na3PO4,
Buffers: Buffers are defined as a compound or a mixture of compounds that resists the pH upon the addition of small quantities of acid or alkali. Buffer have definite pH value. The pH will not change after keeping it for a long period of time. The pH value altered negligibly by the addition of small quantities of acid /base. Buffer action: The resistance to a change in pH is known as buffer action. So buffers can be added to show buffer action. Buffer capacity: The amount of acid/base required to produce a unit change in pH in a solution is called buffer capacity.
Preparation of Buffer Solutions
Mechanism of a Buffering Action • In solution, the salt is completely ionised, and the weak acid is partly ionised. Salt- CH3COONa Na ⇌ + + CH3COO– Acid- CH3COOH H ⇌ + + CH3COO– • On addition of acid, the released protons of acid will be removed by the acetate ions to form an acetic acid molecule. H+ + CH3COO– (from added acid) CH ⇌ 3COOH (from buffer solution) • On addition of the base, the hydroxide released by the base will be removed by the hydrogen ions to form water. HO– + H+ (from added base) H ⇌ 2O (from buffer solution)
Buffer equation Hendersion’s Equation (pH of buffer) • Acidic Buffer: • Consider an acid buffer solution containing a weak acid (HA) and its salt (KA) with a strong base (KOH). Weak acid HA ionises, and the equilibrium can be written as • HA H ⇋ + + A− • Acid dissociation constant = • Ka = [H+ ] [A– ]/HA • ∴ [H+ ] = {Ka [HA]} / [A– ] • Taking negative log both sides, we obtain that – log[H+ ] = – log Ka – log {[HA]/[A– ]} pH = pKa + log {[A– ]/[HA]} pH = pKa + log {[salt] / [acid]} This equation is known as Hendersion’s Equation • Where, Ka = dissociation constant • [A– ] = initial concentration of salt • [HA] = initial concentration of acid
• Basic Buffer: Consider a base buffer solution containing a weak base (B) and its salt (BA) with strong acid. pOH, can be derived as above. BOH B ⇋ + + OH– By the law of chemical equilibrium, Kb = {[B+ ] [OH– ]} / [BOH] ∴ [OH– ] = {Kb [BOH/ [B+ ] • Taking negative log both sides, we obtain that • – log [OH– ] = – log Kb – log {[NH4OH] / [NH4 + ]} • pOH = pKb + log { [NH4 + ] / [NH4OH]} • pOH = pKb + log {[salt] / [base]} • This equation is known as Hendersion’s Equation • Where, Kb = dissociation constant • [NH4 + ] = initial concentration of salt • [NH4OH] = initial concentration of base
Factors Affecting Capacity of Buffer
Van Slyke Equation for determination of Buffer Capacity
Buffers in Pharmaceutical System
SYLLABUS TOPIC: BUFFERED ISOTONIC SOLUTION Buffered isotonic solution: Isotonic buffered solution is defined as a solution which maintains the iso-tonicity and the pH as that of the body fluids. Isotonic buffer solution should be compatible with the body fluids for the following reasons. Blood and lacrimal fluids are in vivo buffer systems. Any solution that comes in contact with these fluids should be buffered to a desired pH, so that these are compatible with the body fluids. Some solutions are meant for the application on delicate membranes of the body. Such solutions may cause haemolysis, tissue irritation, necrosis and tissue toxicity. In such cases, solutions must be just to the same osmotic pressure and tonicity as that of the body fluids.
Preparation of Isotonic Buffer Solution: 1. The drug and other ingredients are dissolved in water. 2. The pH of the solution is determined and adjusted to the desired value. 3. The tonicity value of the solution is calculated procedures using standard procedures. 4. The amount of sodium chloride required to adjust the tonicity is calculated. 5. The required amount of sodium chloride is added to the solution, so that the final solution becomes isotonic. 6. Isotonic diluting solution is added for maintaining the drug concentration to the desired level (dose). 7. If the pH is also needs to be maintained, then buffered isotonic diluting solution is added to make up the desired volume (dose). Since the drug solution is already isotonic, any isotonic diluting solution (electrolytes) can be used to dilute the solution. Some of the isotonic diluting solutions are: Isotonic sodium chloride solution, Dextrose solution, Ringer solution etc The isotonic buffered diluting solutions are available in acidic, neutral and alkaline range. Isotonic buffered diluting solutions are: