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Authored By: Dr. Alex Martin
Ph.D., M.Pharm, FAGE
ARRHENIUS CONCEPT OF ACIDS AND BASES
•
• Accordingly, HCl is a strong acid because it dissociates completely into H+ ions in aqueous solution
• And NaOH is a strong base because it dissociates completely into OH- ions in aqueous solution
LIMITATIONS OFARRHENIUS DEFINTION
The theory does not help to identify acids and bases in non-aqueous enviornment such as the solid or
gas phase
ACIDS
BASES
HCl + H2O H30+ + Cl-
NaOH + H20 Na+ + H2O + OH-
BRONSTED-LOWRY CONCEPT OF ACIDS AND BASES
WHAT WOULD BE THE RESULT OF SUCH INTERACTION..?
PREREQUISITES FOR BEING AN ACID OR BASE
After donation of electron the acid will become the conjugate base
and the base would become conjugate acid.
H-A + B: A: + B-H
(Acid) (Base) (Conjugate Base) (Conjugate Acid)
• Let us study Bronsted-Lowry concept with the aid of an example….
HERE, BRONSTED LOWRY ACID = HCl (IT CONTAINS PROTON)
AND, BRONSTED-LOWRY BASE = NH3 (IT CONTAINS A PAIR OF ELECTRONS)
NH3(g) + HCl (g) NH4Cl(s)
NOTE: ACCORDING TO ARRHENIUS, THE ABOVE REACTION IS NOT
EVEN AN ACID-BASE REACTION….
WATER
• CASE I: WATER ACTS AS A BRONSTED-LOWRY BASE
Reaction between HNO3 and water
• CASE II: WATER ACTS AS A BRONSTED-LOWRY ACID
Reaction between NH3 and water
That whether water would react as an acid or a base depends upon what it is reacting with.
HNO3 + H20 H3O+ + NO3
-
(B-L BASE)
STRONG ACIDS AND WEAK ACIDS
STRONG ACIDS
• A STRONG ACID COMPLETELY DISSOCIATES INTO IT’S CONSTITUENT IONS IN AQUEOUS SOLUTION.
HCl + H20 H3O+ + Cl-
Note the single arrow which indicates
complete dissociation of HCl into
constituent ions
• WEAK ACIDS
WEAK ACIDS PARTIALLY DISSOCIATES INTO ITS CONSTITUENT IONS AND DISSOCIATION IS IN A STATE OF
DYNAMIC EQUILIBRIUM
Eg: Acids like HF and CH3COOH dissociate partially
into its constituent ions.
The arrows are pointed in both direction which indicates that the reaction is in a state of
dynamic equilibrium.
That is, at a particular time there will be a significant concentration of acetic acid
molecules and a smaller fraction of acetate ions in the reaction system which would
remain constant.
STRONG BASE
• A STRONG BASE COMPLETELY DISSOCIATES INTO ITS CONSTITUENT IONS….
NaOH + H2O Na+ + OH- + H20
THE ARROW IS SINGLE DIRECTIONAL ARROW WHICH MEANS THAT THERE WILL
BE NO NaOH LEFT AFTER WE DISSOLVE IT IN WATER.
Only Na+ and OH- will be present in final solution
WEAK BASE
• A WEAK BASE DOES NOT COMPLETELY DISSOCIATE INTO ITS CONSTITUENT IONS.
• Eg: AMMONIA IN WATER
CONJUGATE ACID AND CONJUGATE BASE
• Consider the reaction of HNO3 with H20
• 2 CONJUGATE PAIR:
1. CONJUGATE PAIR I: HNO3 AND NO3
-
2. CONJUGATE PAIR II: H2O AND OH-
• Consider the reaction of NH3 and H2O
• Conjugate pair I : NH3 and NH4
+
• Conjugate pair II: H20 and OH-
HNO3 + H20 H3O+ + NO3
-
(Acid) (Base) (Conjugate acid) (Conjugate Base)
IRREVERSIBLE REACTION
REVERSIBLE REACTION
BUFFER
• LET US ASSUME THAT WE CONDUCT A SIMPLE EXPIREMENT IN LAB……
 SOLUTION A
In solution A (pH = 7), we put HCl pH of Solution A decreases
In solution A(pH = 7), we put NaOH pH increases
PH OF SOLUTION A CHANGES ON ADDITION OF ALKALI OR ACID.
 SOLUTION B
• In solution B (pH = 7) , we put HCl No Change in pH
• In solution B(pH = 7), we put NaOH No Change in Ph
PH OF SOLUTION B RESISTS THE CHANGE IN PH.
WHAT IS THE DIFFERENCE…?
WHILE SOLUTION A IS JUST WATER, SOLUTION B IS A BUFFER………………..
Q.1 WHAT IS BUFFER…..???
• A BUFFER IS AN AQUEOUS SOLUTION THAT RESISTS CHANGE IN pH ON ADDITION OF SMALL AMOUNTS OF ALKALI
OR ACIDS.
Q.2. HOW IS BUFFER PREPARED……???
pH won’t change on boiling of solution
pH won’t change on addition of water
ACIDIC BUFFER = WEAK ACID + CONJUGATE
BASE.
Eg: CH3COOH + CH3COO-
BASIC BUFFER = WEAK BASE + CONJUGATE
ACID
Eg: NH3 + NH4
+
• Q.3. HOW DO BUFFERS ACT…..????
• WHAT HAPPENS WHEN YOU DISSOLVE ACETIC ACID IN WATER….??
• ACETIC ACID BUFFER CONSISTS OF ACETIC ACID AND ITS CONJUGATE BASE, ACETATE ION..
LET US STUDY THIS USING THE EXAMPLE OF ACETIC ACID
BUFFER……
To prepare it, you have to dissolve Acetic acid in water…..
• CASE I: WHAT HAPPENS WHEN AN ACID IS ADDED INTO THIS BUFFER….?
• ACETATE ION REACTS WITH HYDRONIUM ION TO FORM ACETIC ACID WHICH IS ALREADY A
COMPONENT OF THE BUFFER.
• CASE II: WHAT HAPPENS WHEN A BASE IS ADDED INTO THIS BUFFER….?
• ACETIC ACID REACTS WITH HYDROXYL ION TO FORM ACETATE ION WHICH IS ALREADY A COMPONENT
OF THE BUFFER.
H+
OH-
Let us study buffers by taking an example of Basic Buffers…
Let us take the case of NH3- NH4
+ Buffer….
For this, we have to dissolve NH3 in H20…..
• CASE I: WHAT HAPPENS WHEN AN ACID IS ADDED INTO THIS BUFFER SYSTEM……
• IN THIS CASE, THE HYDRONIUM ION REAACTS WITH AMMONIA TO FORM AMMONIUM ION WHICH IS
ALREADY A COMPONENT OF THE BUFFER SYSTEM…
• CASE II: WHAT HAPPENS WHEN A BASE IS ADDED INTO THIS BUFFER SYSTEM….
• THE HYDROXYL ION REACTS WITH AMMONIUM ION TO GIVE AMMONIA WHICH IS ALREADY A
COMPONENT OF THE BUFFER SYSTEM……
H+
OH-
• IN THIS CASE, THERE IS NO CHANGE IN CONCENTRATION OF OH- IONS
• THE DYNAMIC EQILIBRIUM FOLLOWS LE-CHATELIER’S PRINCIPLE……….
H+
OH-
THE BUFFER SYSTEM NUETRALIZES THE HYDRONIUM OR HYDROXYL ION ADDED SO AS
TO RESIST A CHANGE IN pH.
https://byjus.com/jee/le-chateliers-principle-on-equilibrium/
Handerson-Hasselbalch equation.
• Therefore, it is used to calculate the pH of buffers when other parameters are known……
• At equilibrium, [Base] = [Acid]
• Equation becomes…..
pH = pKa at equilibrium……
Similarly, for a basic buffer, the pOH is given as follows….
• At equilibrium, [Acid] = [Base]
• Equation becomes…..
pOH = pKb at equilibrium……
• LIMITATIONS OF HANDERSON-HASSELBACH EQUATION
KNOWN
KNOWN
KNOWN
KNOWN
KNOWN
KNOWN
2. NOT APPLICABLE TO ACIDS THAT CAN DONATE MORE THAN ONE H+ SUCH AS H2SO4,
H3PO4
3. THE SALT (CONJUGATE BASE OR CONJUGATE ACID) COMPLETELY DISSOCIATES IN
SOLUTION. IN ACTUAL PRACTICE, IT IS NOT SO……
Eg: CH3COONa DOES NOT COMPLETELY DISSOCIATE IN WATER
1. Self-ionization of water affect pH , specially when the buffer solution is of less
strength.
Therefore, HH equation is only applicable to buffers of substantial strength
It cannot be used to calculate the pH of strong acid or a strong base
DERIVATION OF HENDERSON-HASSELBACH EQUATION
https://chem.libretexts.org/Bookshelves/Ancillary_Materials/Reference/Organic_Chemistry_Glo
ssary/Henderson-Hasselbach_Equation
BUFFER CAPACITY
• NO. OF MOLES OF ACID OR BASE REQUIRED TO CHANGE THE pH OF A BUFFER SOLUTION BY 1.
• IT IS GIVEN AS NUMBER OF MOLES OF ACID AND BASE ADDED, DIVIDED BY THE CHANGE IN pH AND
THE VOLUME OF BUFFER IN LITRES…..
PHARMACEUTICAL BUFFERS
DRUGS ARE EITHER ACIDIC OR BASIC. THEREFORE, DISSOLVING THEM IN A SOLUTION OF CONSTANT pH
BECOMES NECESSARY.
• WHY MAINTAINING pH IS SO IMPORTANT…..????
PLASMA PROTIENS AND MEMBRANE
PROTIENS ARE VERY SENSITIVE TO pH
ION CHANNELS CAN
MALFUNCTIONS ON CHANGE
IN pH
ACID-BASE HOMEOSTASIS
Stringent measures are taken up by the body to maintain pH.
Our blood is a buffer system. It is called the bicarbonate buffer system.
Lungs can breathe out CO2
and maintain pH
Kidneys can excrete H+
And HCO3
-
Lacrimal fluid has a pH of 6.5 to 7.6
OUR BODY DOES NOT CHANGE pH, NO MATTER WHAT WE EAT…..
Therefore, there is a need to maintain a pH of drugs…
2. PH ALSO LEADS TO CHANGES IN OSMALARITY OF BODY FLUIDS……
H+
WHAT HAPPENS WHEN OSMALARITY OF THE BLOOD CHANGES….???
Therefore, it is very important to maintain pH of medicinal preperations
• PHARMACEUTICAL BUFFER SYSTEM
Drugs are dissolved in buffers of suitable pH before being administered into the body…
Some commonly used pharmaceutical buffer systems are given below:
1. PHOSPHATE BUFFERED SALINE
2. ACETATE BUFFER: CONTAINS CH3COOH AND CH3COONa
3. CITRATE BUFFER: CITRIC ACID AND SODIUM CITRATE (C6H8O7 and C6H707Na)
BUFFER SYSTEM OF PBS
Isotonic with cells; non-toxic
APPLICATION OF PBS
Used in microbiology to dilute cells and to wash containers
containing cells
Storage of microorganisms and viruses
Used in all kinds of eye drops….
Used in Vaginal washes
HOW TO PREPARE BUFFER SOLUTION….???
GENERAL METHOD OF PREPARATION
TONICITY
It is the difference in osmotic pressure of the two solutions that is separated by semi-
permeable membrane.
It decides the direction and extent of the diffusion of water
HOW TO MEASURE TONICITY…..???
TWO METHODS
HAEMOLYTIC METHOD CRYOSCOPIC METHOD
HAEMOLYTIC METHOD: BASED ON CHANGES IN THE SIZE AND SHAPE OF RBC AND THE
RESULTING EFFECT ON THE VOLUME THEY OCCUPY WHEN PLACED IN SOLUTIONS OF
DIFFERENT TONICITY
OR, IT IS BASED ON CHANGE IN VOLUME OCCUPIED BY RBC’S WITH
CHANGE IN SHAPE AND SIZE
TAKE TWO CENTRIFUGAL TUBES.
TUBE A IS FILLED WITH BLOOD AND IS DILUTED WITH 5ML
OF 0.9% W/V OF NaCl SOLUTION (ISOTONIC SOLUTION)
TUBE B IS FILLED WITH BLOOD AND IS DILUTED WITH 5ML OF
TEST SOLUTION
THE TUBES ARE ROTATED AT VERY HIGH SPEEDS……
AFTER CENTRIFUGATION, THE BLOOD CELLS ARE CONCENTRATED
AT ONE END OF CENTRIFUGATION TUBE
PACKED CELL VOLUME (PCV) IS MEASURED FOR BOTH SOLUTIONS AND THE VOLUME ARE
COMPARED WITH EACH OTHER
Tube 1:Isotonic
Tube 2: Test solution
CASE I: NO CHANGE IN VOLUME
IF PACKED CELL VOLUME OF TEST SOLUTION (TUBE B) IS EQUAL TO THAT OF TUBE A, THE
SOLUTION IN TUBE B IS SAID TO BE ISOTONIC
CASE II: VOLUME OF TEST TUBE B IS MORE
IF PACKED CELL VOLUME (PCV) OF TUBE B (TEST SOLUTION) IS MORE THAN THAT OF TUBE
A, THE SOLUTION IS SAID TO BE HYPOTONIC
CRYOSCOPIC METHOD
• THE FREEZING POINT OF WATER = 0°C
• THE FREEZING POINT OF BLOOD = -0.52 °C
• THE FREEZING POINT OF 0.9 % NaCl = -0.52 °C
CASE III: VOLUME OF TUBE B IS LESS
THE VOLUME OF TUBE B (TEST SOLUTION) IS LESS THAN THAT OF TUBE A. IN SUCH CASE,
THE SOLUTION IS SAID TO BE HYPERTONIC…
ADDITION OF SOLUTES TO
WATER DECREASES ITS
FREEZING POINT
PROCEDURE
THE TEST SOLUTION (DRUG) IS FROZEN TO RECORD ITS
FREEZING POINT
RESULTS
1. TAKE TWO TEST TUBES. TUBE A CONTAINS 0.9% NaCl
solution or blood while TUBE B contains drug solution.
2. Record the freezing point of both solutions and compare the values.
CASE III: THE FREEZING POINT IS MORE THAN THAT OF TUBE A
IN SUCH CASE, SOLUTION IN TUBE B IS SAID TO BE HYPOTONIC
METHODS TO ADJUST TONICITY
NaCl or some other substances are added till the freezing point of the solution becomes -
0.52°C and thus the solution becomes isotonic.
It is very important to know the exact tonicity of the drug solution so that exact amount of
NaCl is added such that tonicity is equal to that of blood.
TWO METHODS
Cryoscopic Method NaCl Equivalent Method
I. CRYOSCOPIC METHOD
Not possible to adjust tonicity by altering drug concentration as it can lead to dose
related adverse effects in humans.
The only way to adjust tonicity is to add adjusting agents for tonicity such as NaCl.
Drug solution
Measure ΔTf
ΔTf = a X x
Where, a = Concentration of the drug solution
x = one unit of concentration
x = ΔTf/a
x= ΔTf
If w = grams of adjusting substance that is to be added
Then, ΔTf = w x ΔTf of 1 % solution of adjusting substance
ΔTf = w X b = wb
The drug solution’s tonicity = x; and the adjusting substance’s tonicity = wb.
Adjusting substance is added to drug solution but the sum of the tonicity of them should
not exceed 0.52
i.e., x + wb = 0.52
w = 0.52 – x/b
Remember, b = ΔTf of 1% concentration of adjusting substance
If adjusting substance added is NaCl ,
….then b or ΔTf for 1% solution of NaCl = 0.58
Therefore, w = 0.52-x/0.58
Where, x = ΔTf of 1% drug solution (which is already measured)
Where, P.S.M. = Parent strength of medicament
It is only valid for 100 ml of solution….
THANK YOU…..

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Acid and bases (PCI Syllabus, B.Pharm)

  • 1. Authored By: Dr. Alex Martin Ph.D., M.Pharm, FAGE
  • 2. ARRHENIUS CONCEPT OF ACIDS AND BASES • • Accordingly, HCl is a strong acid because it dissociates completely into H+ ions in aqueous solution • And NaOH is a strong base because it dissociates completely into OH- ions in aqueous solution LIMITATIONS OFARRHENIUS DEFINTION The theory does not help to identify acids and bases in non-aqueous enviornment such as the solid or gas phase ACIDS BASES HCl + H2O H30+ + Cl- NaOH + H20 Na+ + H2O + OH-
  • 3.
  • 4. BRONSTED-LOWRY CONCEPT OF ACIDS AND BASES WHAT WOULD BE THE RESULT OF SUCH INTERACTION..? PREREQUISITES FOR BEING AN ACID OR BASE After donation of electron the acid will become the conjugate base and the base would become conjugate acid. H-A + B: A: + B-H (Acid) (Base) (Conjugate Base) (Conjugate Acid)
  • 5. • Let us study Bronsted-Lowry concept with the aid of an example…. HERE, BRONSTED LOWRY ACID = HCl (IT CONTAINS PROTON) AND, BRONSTED-LOWRY BASE = NH3 (IT CONTAINS A PAIR OF ELECTRONS) NH3(g) + HCl (g) NH4Cl(s) NOTE: ACCORDING TO ARRHENIUS, THE ABOVE REACTION IS NOT EVEN AN ACID-BASE REACTION….
  • 6. WATER • CASE I: WATER ACTS AS A BRONSTED-LOWRY BASE Reaction between HNO3 and water • CASE II: WATER ACTS AS A BRONSTED-LOWRY ACID Reaction between NH3 and water That whether water would react as an acid or a base depends upon what it is reacting with. HNO3 + H20 H3O+ + NO3 - (B-L BASE)
  • 7. STRONG ACIDS AND WEAK ACIDS STRONG ACIDS • A STRONG ACID COMPLETELY DISSOCIATES INTO IT’S CONSTITUENT IONS IN AQUEOUS SOLUTION. HCl + H20 H3O+ + Cl- Note the single arrow which indicates complete dissociation of HCl into constituent ions
  • 8. • WEAK ACIDS WEAK ACIDS PARTIALLY DISSOCIATES INTO ITS CONSTITUENT IONS AND DISSOCIATION IS IN A STATE OF DYNAMIC EQUILIBRIUM Eg: Acids like HF and CH3COOH dissociate partially into its constituent ions. The arrows are pointed in both direction which indicates that the reaction is in a state of dynamic equilibrium. That is, at a particular time there will be a significant concentration of acetic acid molecules and a smaller fraction of acetate ions in the reaction system which would remain constant.
  • 9. STRONG BASE • A STRONG BASE COMPLETELY DISSOCIATES INTO ITS CONSTITUENT IONS…. NaOH + H2O Na+ + OH- + H20 THE ARROW IS SINGLE DIRECTIONAL ARROW WHICH MEANS THAT THERE WILL BE NO NaOH LEFT AFTER WE DISSOLVE IT IN WATER. Only Na+ and OH- will be present in final solution
  • 10. WEAK BASE • A WEAK BASE DOES NOT COMPLETELY DISSOCIATE INTO ITS CONSTITUENT IONS. • Eg: AMMONIA IN WATER
  • 11. CONJUGATE ACID AND CONJUGATE BASE • Consider the reaction of HNO3 with H20 • 2 CONJUGATE PAIR: 1. CONJUGATE PAIR I: HNO3 AND NO3 - 2. CONJUGATE PAIR II: H2O AND OH- • Consider the reaction of NH3 and H2O • Conjugate pair I : NH3 and NH4 + • Conjugate pair II: H20 and OH- HNO3 + H20 H3O+ + NO3 - (Acid) (Base) (Conjugate acid) (Conjugate Base) IRREVERSIBLE REACTION REVERSIBLE REACTION
  • 12. BUFFER • LET US ASSUME THAT WE CONDUCT A SIMPLE EXPIREMENT IN LAB……  SOLUTION A In solution A (pH = 7), we put HCl pH of Solution A decreases In solution A(pH = 7), we put NaOH pH increases PH OF SOLUTION A CHANGES ON ADDITION OF ALKALI OR ACID.  SOLUTION B • In solution B (pH = 7) , we put HCl No Change in pH • In solution B(pH = 7), we put NaOH No Change in Ph PH OF SOLUTION B RESISTS THE CHANGE IN PH. WHAT IS THE DIFFERENCE…? WHILE SOLUTION A IS JUST WATER, SOLUTION B IS A BUFFER………………..
  • 13. Q.1 WHAT IS BUFFER…..??? • A BUFFER IS AN AQUEOUS SOLUTION THAT RESISTS CHANGE IN pH ON ADDITION OF SMALL AMOUNTS OF ALKALI OR ACIDS. Q.2. HOW IS BUFFER PREPARED……??? pH won’t change on boiling of solution pH won’t change on addition of water ACIDIC BUFFER = WEAK ACID + CONJUGATE BASE. Eg: CH3COOH + CH3COO- BASIC BUFFER = WEAK BASE + CONJUGATE ACID Eg: NH3 + NH4 +
  • 14. • Q.3. HOW DO BUFFERS ACT…..???? • WHAT HAPPENS WHEN YOU DISSOLVE ACETIC ACID IN WATER….?? • ACETIC ACID BUFFER CONSISTS OF ACETIC ACID AND ITS CONJUGATE BASE, ACETATE ION.. LET US STUDY THIS USING THE EXAMPLE OF ACETIC ACID BUFFER…… To prepare it, you have to dissolve Acetic acid in water…..
  • 15. • CASE I: WHAT HAPPENS WHEN AN ACID IS ADDED INTO THIS BUFFER….? • ACETATE ION REACTS WITH HYDRONIUM ION TO FORM ACETIC ACID WHICH IS ALREADY A COMPONENT OF THE BUFFER. • CASE II: WHAT HAPPENS WHEN A BASE IS ADDED INTO THIS BUFFER….? • ACETIC ACID REACTS WITH HYDROXYL ION TO FORM ACETATE ION WHICH IS ALREADY A COMPONENT OF THE BUFFER. H+ OH-
  • 16. Let us study buffers by taking an example of Basic Buffers… Let us take the case of NH3- NH4 + Buffer…. For this, we have to dissolve NH3 in H20…..
  • 17. • CASE I: WHAT HAPPENS WHEN AN ACID IS ADDED INTO THIS BUFFER SYSTEM…… • IN THIS CASE, THE HYDRONIUM ION REAACTS WITH AMMONIA TO FORM AMMONIUM ION WHICH IS ALREADY A COMPONENT OF THE BUFFER SYSTEM… • CASE II: WHAT HAPPENS WHEN A BASE IS ADDED INTO THIS BUFFER SYSTEM…. • THE HYDROXYL ION REACTS WITH AMMONIUM ION TO GIVE AMMONIA WHICH IS ALREADY A COMPONENT OF THE BUFFER SYSTEM…… H+ OH-
  • 18. • IN THIS CASE, THERE IS NO CHANGE IN CONCENTRATION OF OH- IONS • THE DYNAMIC EQILIBRIUM FOLLOWS LE-CHATELIER’S PRINCIPLE………. H+ OH- THE BUFFER SYSTEM NUETRALIZES THE HYDRONIUM OR HYDROXYL ION ADDED SO AS TO RESIST A CHANGE IN pH. https://byjus.com/jee/le-chateliers-principle-on-equilibrium/
  • 19. Handerson-Hasselbalch equation. • Therefore, it is used to calculate the pH of buffers when other parameters are known…… • At equilibrium, [Base] = [Acid] • Equation becomes….. pH = pKa at equilibrium…… Similarly, for a basic buffer, the pOH is given as follows…. • At equilibrium, [Acid] = [Base] • Equation becomes….. pOH = pKb at equilibrium…… • LIMITATIONS OF HANDERSON-HASSELBACH EQUATION KNOWN KNOWN KNOWN KNOWN KNOWN KNOWN
  • 20. 2. NOT APPLICABLE TO ACIDS THAT CAN DONATE MORE THAN ONE H+ SUCH AS H2SO4, H3PO4 3. THE SALT (CONJUGATE BASE OR CONJUGATE ACID) COMPLETELY DISSOCIATES IN SOLUTION. IN ACTUAL PRACTICE, IT IS NOT SO…… Eg: CH3COONa DOES NOT COMPLETELY DISSOCIATE IN WATER 1. Self-ionization of water affect pH , specially when the buffer solution is of less strength. Therefore, HH equation is only applicable to buffers of substantial strength It cannot be used to calculate the pH of strong acid or a strong base DERIVATION OF HENDERSON-HASSELBACH EQUATION https://chem.libretexts.org/Bookshelves/Ancillary_Materials/Reference/Organic_Chemistry_Glo ssary/Henderson-Hasselbach_Equation
  • 21. BUFFER CAPACITY • NO. OF MOLES OF ACID OR BASE REQUIRED TO CHANGE THE pH OF A BUFFER SOLUTION BY 1. • IT IS GIVEN AS NUMBER OF MOLES OF ACID AND BASE ADDED, DIVIDED BY THE CHANGE IN pH AND THE VOLUME OF BUFFER IN LITRES….. PHARMACEUTICAL BUFFERS DRUGS ARE EITHER ACIDIC OR BASIC. THEREFORE, DISSOLVING THEM IN A SOLUTION OF CONSTANT pH BECOMES NECESSARY. • WHY MAINTAINING pH IS SO IMPORTANT…..????
  • 22. PLASMA PROTIENS AND MEMBRANE PROTIENS ARE VERY SENSITIVE TO pH ION CHANNELS CAN MALFUNCTIONS ON CHANGE IN pH ACID-BASE HOMEOSTASIS Stringent measures are taken up by the body to maintain pH. Our blood is a buffer system. It is called the bicarbonate buffer system. Lungs can breathe out CO2 and maintain pH Kidneys can excrete H+ And HCO3 -
  • 23. Lacrimal fluid has a pH of 6.5 to 7.6 OUR BODY DOES NOT CHANGE pH, NO MATTER WHAT WE EAT….. Therefore, there is a need to maintain a pH of drugs… 2. PH ALSO LEADS TO CHANGES IN OSMALARITY OF BODY FLUIDS…… H+ WHAT HAPPENS WHEN OSMALARITY OF THE BLOOD CHANGES….???
  • 24. Therefore, it is very important to maintain pH of medicinal preperations
  • 25. • PHARMACEUTICAL BUFFER SYSTEM Drugs are dissolved in buffers of suitable pH before being administered into the body… Some commonly used pharmaceutical buffer systems are given below: 1. PHOSPHATE BUFFERED SALINE 2. ACETATE BUFFER: CONTAINS CH3COOH AND CH3COONa 3. CITRATE BUFFER: CITRIC ACID AND SODIUM CITRATE (C6H8O7 and C6H707Na) BUFFER SYSTEM OF PBS
  • 26. Isotonic with cells; non-toxic APPLICATION OF PBS Used in microbiology to dilute cells and to wash containers containing cells Storage of microorganisms and viruses Used in all kinds of eye drops…. Used in Vaginal washes
  • 27. HOW TO PREPARE BUFFER SOLUTION….??? GENERAL METHOD OF PREPARATION
  • 28. TONICITY It is the difference in osmotic pressure of the two solutions that is separated by semi- permeable membrane. It decides the direction and extent of the diffusion of water
  • 29. HOW TO MEASURE TONICITY…..??? TWO METHODS HAEMOLYTIC METHOD CRYOSCOPIC METHOD HAEMOLYTIC METHOD: BASED ON CHANGES IN THE SIZE AND SHAPE OF RBC AND THE RESULTING EFFECT ON THE VOLUME THEY OCCUPY WHEN PLACED IN SOLUTIONS OF DIFFERENT TONICITY OR, IT IS BASED ON CHANGE IN VOLUME OCCUPIED BY RBC’S WITH CHANGE IN SHAPE AND SIZE
  • 30. TAKE TWO CENTRIFUGAL TUBES. TUBE A IS FILLED WITH BLOOD AND IS DILUTED WITH 5ML OF 0.9% W/V OF NaCl SOLUTION (ISOTONIC SOLUTION) TUBE B IS FILLED WITH BLOOD AND IS DILUTED WITH 5ML OF TEST SOLUTION THE TUBES ARE ROTATED AT VERY HIGH SPEEDS……
  • 31. AFTER CENTRIFUGATION, THE BLOOD CELLS ARE CONCENTRATED AT ONE END OF CENTRIFUGATION TUBE PACKED CELL VOLUME (PCV) IS MEASURED FOR BOTH SOLUTIONS AND THE VOLUME ARE COMPARED WITH EACH OTHER Tube 1:Isotonic Tube 2: Test solution CASE I: NO CHANGE IN VOLUME IF PACKED CELL VOLUME OF TEST SOLUTION (TUBE B) IS EQUAL TO THAT OF TUBE A, THE SOLUTION IN TUBE B IS SAID TO BE ISOTONIC CASE II: VOLUME OF TEST TUBE B IS MORE IF PACKED CELL VOLUME (PCV) OF TUBE B (TEST SOLUTION) IS MORE THAN THAT OF TUBE A, THE SOLUTION IS SAID TO BE HYPOTONIC
  • 32. CRYOSCOPIC METHOD • THE FREEZING POINT OF WATER = 0°C • THE FREEZING POINT OF BLOOD = -0.52 °C • THE FREEZING POINT OF 0.9 % NaCl = -0.52 °C CASE III: VOLUME OF TUBE B IS LESS THE VOLUME OF TUBE B (TEST SOLUTION) IS LESS THAN THAT OF TUBE A. IN SUCH CASE, THE SOLUTION IS SAID TO BE HYPERTONIC… ADDITION OF SOLUTES TO WATER DECREASES ITS FREEZING POINT PROCEDURE THE TEST SOLUTION (DRUG) IS FROZEN TO RECORD ITS FREEZING POINT RESULTS 1. TAKE TWO TEST TUBES. TUBE A CONTAINS 0.9% NaCl solution or blood while TUBE B contains drug solution. 2. Record the freezing point of both solutions and compare the values.
  • 33. CASE III: THE FREEZING POINT IS MORE THAN THAT OF TUBE A IN SUCH CASE, SOLUTION IN TUBE B IS SAID TO BE HYPOTONIC METHODS TO ADJUST TONICITY NaCl or some other substances are added till the freezing point of the solution becomes - 0.52°C and thus the solution becomes isotonic. It is very important to know the exact tonicity of the drug solution so that exact amount of NaCl is added such that tonicity is equal to that of blood. TWO METHODS Cryoscopic Method NaCl Equivalent Method I. CRYOSCOPIC METHOD Not possible to adjust tonicity by altering drug concentration as it can lead to dose related adverse effects in humans. The only way to adjust tonicity is to add adjusting agents for tonicity such as NaCl.
  • 34. Drug solution Measure ΔTf ΔTf = a X x Where, a = Concentration of the drug solution x = one unit of concentration x = ΔTf/a x= ΔTf If w = grams of adjusting substance that is to be added Then, ΔTf = w x ΔTf of 1 % solution of adjusting substance ΔTf = w X b = wb The drug solution’s tonicity = x; and the adjusting substance’s tonicity = wb. Adjusting substance is added to drug solution but the sum of the tonicity of them should not exceed 0.52 i.e., x + wb = 0.52
  • 35. w = 0.52 – x/b Remember, b = ΔTf of 1% concentration of adjusting substance If adjusting substance added is NaCl , ….then b or ΔTf for 1% solution of NaCl = 0.58 Therefore, w = 0.52-x/0.58 Where, x = ΔTf of 1% drug solution (which is already measured) Where, P.S.M. = Parent strength of medicament It is only valid for 100 ml of solution….
  • 36.