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BUFFERS
Buffers
are defined as compound or mixture of compounds that by their presence in solution resist the changes in pH upon addition of small quantities of acid or alkali.
Buffer action.
Resistance to change in pH is known as buffer action.
When Acid or alkali added to water/Sodium chloride drastic change in pH of solution. Such systems have no buffer action
Buffer capacity
Amount of acid or base required to produce a unit change in pH of Solution.
BUFFERS ( contd
Characteristic of Buffers
a) Definite pH value ( by dissolving known amount compound) b) pH value of buffer does not alter after long time storage or dilution. c) pH value of buffers slightly altered by addition of small quantities of acids and bases.
Applications
Enhancing solubility-if pH of solution not adjusted properly , drug may precipitate Improving stability-many drugs hydrolyze in aqueous solution .adjusting pH of solution stabilizes such drugs Improving purity-protein purification Optimizing biological activity-enzymes have max stability at definite pH Comforting the body-if pH of solution greatly differs from normal pH of relevant body fluid cause irritation, hence pH of formulation should match with pH of physiological solution
Buffer Applications
1. Should be controlled in formulation of eye drops, ear drops, injections and liquid orals. e. g.
Acetified syrup --- 5.0- 7.2 Dextrose injection --- 3.5 6.5 Oxymetzoline nasal drops -- 4.0 -6.5 Chloramphenicol eye drops ---- 7.0 7.5
Buffer Applications
Enhancing the solubility :
if pH is not maintained Drug may precipitate
Sodium salicylate precipitates as salicylic acid when acidified. Acidic drugs more soluble in basic medium and vice versa.
Buffer Applications
Improving purity :
Proteins are least soluble at their isoelectric point.
Insulin precipitates from aqueous soln. at pH 5.0-6.0. Used for purification of insulin.
Storage of products
Glass containers impart alkalinity to products.
c. Two salts act as acid base pair which can function either as (a) or (b)
Solution of Monobasic potassium Phosphate (KH2PO4) and Dibasic potassium Phosphate (K2HPO 4)
BUFFER SYSTEMS -COMPOSITIONS (contd .) Mainly borates, citrate, phosphate and phthalate salts used in pharmacy. Ionic strength of buffer is adjusted to definite value by adding sodium chloride and pot. Chloride.
Some soln. of drug themselves manifest buffer action
Ephedrine weak base in acidic media forms a salt ephedrine Hydrochloride. Salicylic acid stored in soft glass bottle sodium ions in the container react to sodium salicylate.
Buffer action maintained when small amount of acid or base added. Process continues until entire acetate or acetic acid consumed. Buffer action is limited.
Ampholytic Substances
That are capable acting both as acid and base. e.g.. Glycine act as acid
NH2CH2COOH + H2O Glycine act as base NH2CH2COO- + H3O+ NH2CH2COO- +H3O+ NH3+CH2COO- +H2O
(Zwitter Ions or Dipolar ions)
Ions react with H3O+ ions or OH- and nullify the influence of added substance.
Buffer capacity
Buffer capacity is defined as the ratio of the increment of the strong base (or Acid) to the small change in pH brought about by this addition. F = ( B /(pH B=Concentration of Base or acid added (gram equivalent / lit.) F=1, when 1g equivalent of strong base or strong acid added to one lit. of buffer solution. If the change in pH is 1 unit. Buffer has its greatest capacity when salt and acid concentration are Equal. Therefore H.H. equation; pH = pKa B.C. not a fixed value it depends on the concentration of base added. BC also depends on the Total concentration of buffer constituents. Greater the concentration of salt and acid, the greater is the buffer capacity. (buffer expressed in molar conc.- 0.2M, 0.02M)
C- Total buffer concentration Sum of molar con. Of acid and salt. The maximum buffer capacity occurs when pH = pKa Then [H30+]=Ka hence below equation changes to
Urine
pH :6 (4.5-7.8) pH is low-hydrogen ions excreted by kidneys, high Hydrogen ions retained in kidneys.
IMP.
Relatively small change for acidic buffer In alkaline buffer changes are more marked owing to presence of pKw term in buffer equation.
Ionic strength
Addition of neutral salts changes the pH of solution due to altered ionic strength. Dilution of buffer - changes the pH of solution due to altered ionic strength. So when ever the pH of buffer soln. is mentioned ionic strength also must be specified.
Pharmaceutical Buffers
Formulation of ophthalmic preparation.
Boric acid , Sodium borate and sufficient sodium chloride to make the mixture isotonic. pH range is 7.0 to 9.0
Pharmacopoeia gives elaborate list of Buffers and their method of preparation. Refer Pharmacopoeia
IMP.
Pharmaceutical Buffers
Choice of pharmaceutical buffers depend on the following factors
Availability of chemicals Sterility of final solution Stability of drug Stability of buffer on aging Cost of material Freedom from toxicity E.g. Borate buffer cannot be used to stabilize the oral or parenteral solution because of toxic effects.
The experimental pH values slightly differ form calculated pH values using buffer equation
4. 5.
The ingredients should be dissolved in carbon dioxide free water and allowed some time to establish equilibrium. pH and Buffer capacity of the completed buffer solution to be verified. The procedure remain same for basic buffers.
Iso-osmotic solutions
Are those solutions which produce the same osmotic pressure as that of cell content in question -but solvent permeable through the cell membrane their by altering tone of the cell Example-1.8% solution of urea Iso osmotic means It does not necessarily isotonic 1.8% urea soln. has same Iso-osmotic pressure that of 0.9% Nacl solution, but not isotonic solution 1.8% urea solution produces haemolysis due to permeability of water
Isotonic solutions
Are those solutions which produce the same osmotic pressure as that of cell contents in question without net gain or loss of water by both the solution-provided cell membrane impermeable to solutes Isotonic solutions are Iso-osmotic as well as isotonic with cells and membrane
2.0% NaCl Solution (hypertonic) 0.2% NaCl Solution (hypotonic) Isotonic Eq. Equal Osmotic Pressure
0.9% w/v Sodium chloride solution 5.0% w/v Dextrose solution 2.0% w/v Boric acid solution
Hypertonic solutions
Defined as those solutions containing the solute in higher conc. than that is required for isotonic solutions Which causes red blood cell -shrinkage
Hypotonic solutions
Defined as those solutions containing the solute in lower concentration than that is required for isotonic solutions Cause red blood cell to burst- hemolysis
Measurement of tonicity
Isotonicity value: Con. Of an aqueous NaCl solution having the same colligative property as the solution in question. Apart form Nacl no of chemicals and drugs used in the formulation These ingredients contribute to tonicity of solution Methods are needed for verifying the tonicity and adjusting the isotonicity of the solution Determination of tonicity Hemolytic method Cryoscopic method or Depression of freezing point.
Colligative properties
Lowering of volatile point Elevation of boiling point Depression of freezing point Osmotic pressure of solution These properties depend on no of particles and not on the nature of solvent
Used to determine isotonicity values Freezing point of water 0r C, when Sodium chloride added-freezing point decreases. The depression of FP of blood ( o.52 rC), the drug solution should have FP similar to blood ( o.52 rC). Same osmotic pressure as blood.
Tf = L C
OR
L =
Tf / C
The L value is obtained from the freezing point lowering of a solution of a compound that is isotonic with blood or lacrimal fluid The specific value for L is represented by L iso which is defined as the specific value of L which is equal to i K f at a con. of drug which is isotonic with blood and lacrimal fluid L iso value for 0.9% Nacl whose FD is O.52 -0.5/ 0.154= 3.4 L = Tf / C 0.154 is molar conc. of 0.9% w/v Nacl
Class- I
Class-II
Class- I
Class-II