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Lacrimal fluid has good buffering capacity Most ophthalmic drugs are WA/WB: At low pH:
dissociation: solution: stable
But therapeutic effect is lowered
• pH and solubility*
• Influence of buffering on the solubility of base
• At a low pH : base is in the ionic form & 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 soln.
• Base soln. should be buffered at a sufficiently low
pH for stabilization against precipitation.
Pharmaceutical Buffer
• Buffers in Tablet:
• To control the pH in the microenvironment
surrounding the drug particles
• Formulation containing acidic drug
• to reduce gastric irritation
• Antacid : Sodium bicarbonate,magnesium
carbonate
Preparation of pharmaceutical buffer
solutions
• Steps for development of a new buffer
• ① Select a weak acid having a pKa approximately
equal to the pH at which the buffer is to be used.
• ② Calculate the ratio of salt & weak acid required to
obtain the desired pH.
• ③ Consider the individual conc. Of the buffer salt &
acid needed to obtain a suitable buffer capacity*
• Individual conc. : 0.05 ~ 0.5M*
• buffer capacity : 0.01 ~ 0.1
Preparation of pharmaceutical buffer
solutions
• Steps for development of a new buffer
• ④ Availability of chemicals, sterility of the
final soln, stability of the drug & buffer, cost of
materials, freedom from toxicityex) borate
buffer – toxic effect – not be used for oral or
parenteral products.
• ⑤ Determine the pH and buffer capacity
using a reliable pH meter
Physiologically isotonic Solution: 0.9% Nacl
Haemo
Direct proportion to the number of cell haemolysed
Suspended in solution whose tonicity is to be determine
Solution having same tonicity exhibits similar behavior with respect to
their colligative properties such as lowering vapour pressure, depression i
freezing point
Measurement of Tonicity
• Measurement of the slight temperature differences
• One of the first references to the determination of
the freezing point of blood and tears (as was
necessary to make solutions isotonic with these
fluids) is that -0.52°C is the freezing point of both
human blood and lacrimal fluid.
• This temperature corresponds to the freezing point
of a 0.90% NaCl solution, which is therefore
considered to be isotonic with both blood and
lacrimal fluid.
3)Calculating Tonicity Using Liso Values
• Because the freezing point depressions for solutions of electrolytes of
both the weak and strong types are always greater than those calculated
from the equation
• ΔTf= Kfc,
• ΔTf= depression in freezing point
• Kf= molal depression constant
• C= molar concentration
• a new factor, L = iKf,
• is introduced to overcome this difficulty.
• The equation, already discussed is
• The L value can be obtained from the freezing point lowering of solutions
of representative compounds of a given ionic type at a concentration c
that is isotonic with body fluids. This specific value of L is written as Liso.
Methods of Adjusting Tonicity and pH
• One of several methods can be used to calculate
the quantity of sodium chloride, dextrose, and
other substances that may be added to solutions
of drugs to render them isotonic.
• The methods are divided into two classes.
• 1. class I methods
• 2. Class II methods
Methods of Adjusting Tonicity and pH
• Class I methods: sodium chloride or some
other substance is added to the solution of
the drug to lower the freezing point of the
solution to -0.52°C and thus make it isotonic
with body fluids. Under this class are included
the
• A. Cryoscopic method
• B. sodium chloride equivalent method
Methods of Adjusting Tonicity and pH
• In the class II methods,
• water is added to the drug in a sufficient
amount to form an isotonic solution. The
preparation is then brought to its final volume
with an isotonic or a buffered isotonic dilution
solution.
• 1.White–Vincent method and
• 2. Sprowls method.
Class I Methods
• a)Cryoscopic Method
• Example- If 1% w/v solution of Nacl has freezing
point depression of 0.576 ᵒC; calculate the
concentration of Nacl required in making this
solution isotonic.
• Solution: Since the freezing point of depression of
blood is 0.52ᵒC, the concentration of Nacl
required to make this solution isotonic is
calculated as:
• Concentration of Nacl = 0.52/0.576 = 0.9% w/v
The concentration of Nacl required to this make
isotonic is 0.9%w/v.

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Buffer

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  • 28.
  • 29.
  • 30. Lacrimal fluid has good buffering capacity Most ophthalmic drugs are WA/WB: At low pH: dissociation: solution: stable But therapeutic effect is lowered
  • 31. • pH and solubility* • Influence of buffering on the solubility of base • At a low pH : base is in the ionic form & 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 soln. • Base soln. should be buffered at a sufficiently low pH for stabilization against precipitation.
  • 32. Pharmaceutical Buffer • Buffers in Tablet: • To control the pH in the microenvironment surrounding the drug particles • Formulation containing acidic drug • to reduce gastric irritation • Antacid : Sodium bicarbonate,magnesium carbonate
  • 33. Preparation of pharmaceutical buffer solutions • Steps for development of a new buffer • ① Select a weak acid having a pKa approximately equal to the pH at which the buffer is to be used. • ② Calculate the ratio of salt & weak acid required to obtain the desired pH. • ③ Consider the individual conc. Of the buffer salt & acid needed to obtain a suitable buffer capacity* • Individual conc. : 0.05 ~ 0.5M* • buffer capacity : 0.01 ~ 0.1
  • 34. Preparation of pharmaceutical buffer solutions • Steps for development of a new buffer • ④ Availability of chemicals, sterility of the final soln, stability of the drug & buffer, cost of materials, freedom from toxicityex) borate buffer – toxic effect – not be used for oral or parenteral products. • ⑤ Determine the pH and buffer capacity using a reliable pH meter
  • 35.
  • 37.
  • 38. Haemo
  • 39.
  • 40. Direct proportion to the number of cell haemolysed Suspended in solution whose tonicity is to be determine Solution having same tonicity exhibits similar behavior with respect to their colligative properties such as lowering vapour pressure, depression i freezing point
  • 41. Measurement of Tonicity • Measurement of the slight temperature differences • One of the first references to the determination of the freezing point of blood and tears (as was necessary to make solutions isotonic with these fluids) is that -0.52°C is the freezing point of both human blood and lacrimal fluid. • This temperature corresponds to the freezing point of a 0.90% NaCl solution, which is therefore considered to be isotonic with both blood and lacrimal fluid.
  • 42. 3)Calculating Tonicity Using Liso Values • Because the freezing point depressions for solutions of electrolytes of both the weak and strong types are always greater than those calculated from the equation • ΔTf= Kfc, • ΔTf= depression in freezing point • Kf= molal depression constant • C= molar concentration • a new factor, L = iKf, • is introduced to overcome this difficulty. • The equation, already discussed is • The L value can be obtained from the freezing point lowering of solutions of representative compounds of a given ionic type at a concentration c that is isotonic with body fluids. This specific value of L is written as Liso.
  • 43.
  • 44. Methods of Adjusting Tonicity and pH • One of several methods can be used to calculate the quantity of sodium chloride, dextrose, and other substances that may be added to solutions of drugs to render them isotonic. • The methods are divided into two classes. • 1. class I methods • 2. Class II methods
  • 45. Methods of Adjusting Tonicity and pH • Class I methods: sodium chloride or some other substance is added to the solution of the drug to lower the freezing point of the solution to -0.52°C and thus make it isotonic with body fluids. Under this class are included the • A. Cryoscopic method • B. sodium chloride equivalent method
  • 46. Methods of Adjusting Tonicity and pH • In the class II methods, • water is added to the drug in a sufficient amount to form an isotonic solution. The preparation is then brought to its final volume with an isotonic or a buffered isotonic dilution solution. • 1.White–Vincent method and • 2. Sprowls method.
  • 47. Class I Methods • a)Cryoscopic Method
  • 48. • Example- If 1% w/v solution of Nacl has freezing point depression of 0.576 ᵒC; calculate the concentration of Nacl required in making this solution isotonic. • Solution: Since the freezing point of depression of blood is 0.52ᵒC, the concentration of Nacl required to make this solution isotonic is calculated as: • Concentration of Nacl = 0.52/0.576 = 0.9% w/v The concentration of Nacl required to this make isotonic is 0.9%w/v.