BUFFERs

Factors affecting the pH of buffer solution

1. Temperature
E.g.- an increase in pH was found in case of acetate buffer with increase in
temperature

2. Addition of neutral salts- change the ionic strength and thus change the pH

3. Dilution of buffer with water- causes an alteration in activity coefficient and

causes a small deviation in pH
 BUFFER IN
PHARMACEUTICALS
 Buffer in Biological system

 The pH of blood is maintained at about 7.4 inspite of various acids and bases
reaction going in our body .
 The buffer action is due to the presence of carbonic acid (H2CO3), bicarbonate
ion (HCO3-) and CO2 in the blood)
 Buffer in Pharmaceutical system

 It is essential to control the pH of some solution which find use in pharmaceutical

chemistry and practice.
 These buffer solutions can be categorized into 2 types-

1.Standard buffer system: to provide a solution having a pH for analytical

purpose.

2.Actual buffer system: to maintain the pH limits in pharmaceutical

preparations.

* The pH of pharmaceutical preparations must be controlled to maintain their

chemical stability and solubility of their ingredients and also for their patient’s
comfort.
 Buffer in Pharmaceutical system

1.Volatile substances such as NH3 or CO2 should be avoided because if they

escape from pharmaceutical preparations, they will alter the pH and buffer
capacity of the system.

2.Precautions have to be taken so that alkaline buffers should be protected from

CO2 absorption which would otherwise cause a drop in pH.

3.There are certain medias which can serve as nutrient media for growth of
certain microorganisms, especially when pH is close to neutrality. In order to
prevent this, such solutions are preserved with low concentrations of quaternary
ammonium antimicrobial agents. E.g.- 0.002% benzalkonium chloride.
* In general, parentral solutions need not be buffered when administered into the blood.
However, if they are buffered, low capacity buffers are used.
 Stability of Buffer Solution

 The typical shelf-life for commercial technical buffers is 2 years unopened and 3-6
months open.
 The typical shelf-life for alkaline buffers is 1 month after open because alkaline buffer
will change their pH noticeably when they come into contact with carbon dioxide in the
air.
To maintain the stability of buffer solution, following points must be taken care-
 Check any expiration date on your commercial buffer solution before using it.
 If you are making up a buffers solution, put a date on the label and also an expiration
date.
 Keep your buffer solutions in closed plastic containers or within stoppered
flasks/bottles.
 Store the buffers at room temperature, 15 to 25 °C.
 For alkaline buffers, it's recommended to put the bottles in the refrigerator (2 to 8 °C).
 Avoid storage close to a window or to a heat source.
BUFFERED ISOTONIC SOLUTION
 OSMOSIS

 Osmosis is the net movement of water across a semipermeable membrane

from an area of lower solute concentration to an area of higher solute
concentration

 Osmosis occurs when two solutions, containing different concentration

of solute, are separated by a selectively permeable
membrane. Solvent molecules pass preferentially through the membrane from
the low-concentration solution to the solution with higher solute
concentration. The transfer of solvent molecules will continue until
equilibrium is attained.

 Osmotic pressure is the minimum pressure which needs to be applied to

a solution to prevent the inward flow of its pure solvent across
a semipermeable membrane. It is also defined as the measure of the tendency
of a solution to take in pure solvent by osmosis.
TONICITY

 The ability of an extracellular solution to make water move into or out of a cell
by osmosis is know as its tonicity.

 A solution's tonicity is related to its osmolarity, which is the total

concentration of all solutes in the solution.
 A solution with low osmolarity has fewer solute particles per liter of
solution, while a solution with high osmolarity has more solute particles
per liter of solution.

 Tonicity is a measure of the relative concentration of solute particles on either

side of a semi permeable membrane (e.g. inside a cell versus outside the cell)
TONICITY
Three terms hypotonic, isotonic, and hypertonic are used to compare the osmolarity of a
cell to the osmolarity of the extracellular fluid around it.

1. Hypotonic solution: If the extracellular fluid has lower osmolarity than the fluid inside
the cell, it’s said to be hypotonic- hypo means less than to the
cell, and the net flow of water will be into the cell.

2. Hypertonic solution: In the reverse case, if the extracellular fluid has a higher
osmolarity than the cell’s cytoplasm, it’s said to be hypertonic-
hyper means greater than to the cell, and water will move out
of the cell to the region of higher solute concentration.

3. Isotonic solution: In an isotonic solution- iso means the same the extracellular fluid
has the same osmolarity as the cell, and there will be no net
movement of water into or out of the cell.
 Pharmaceutical preparations intended for application to delicate membranes in
the body should be adjusted to the same osmotic pressure of the body fluids. In
such formulations, isotonic buffer solutions are used.

 These isotonic buffer solutions are of 4 types-

1. Isotonic buffer solution 1: has pH=4.7, used for API such as epinephrine,
cocaine, etc.

2. Isotonic buffer solution 2: has pH=6.8, used for API such as pilocarpine.

3. Isotonic buffer solution 3: has pH=7.4, used for drugs stable in neutral
solution.

4. Isotonic buffer solution 4: has pH=9, used for API such as ophthalmic drugs.
Measurement of Tonicity
 Tonicity is a measure of the relative concentration of solute particles on either side
of a semi permeable membrane (e.g. inside a cell versus outside the cell).

 Only the solutes that can not cross the membrane contribute to the tonicity.

 The higher the tonicity, the greater the difference in the concentration of solutes
and therefore the concentration of water.

 Tonicity is generally classified in 3 ranges-

a) Hypertonicity
b) Hypotonicity
c) Isotonicity
Measurement of Tonicity
The tonicity of the solution can be calculated by 1 of the 3 methods:

1. Haemolytic method
2. Measurement of slight temperature differences
3. Calculating tonicity using Liso values
Measurement of Tonicity

1. Haemolytic method: The effect of various solutions of the drug is observed on

the appearance of red blood cells suspended in the solutions.
A quantitative method developed by Hunter was used based on the fact that a
hypotonic solution liberates oxyhemoglobin in direct proportion to the number of
cells hemolyzed. The Van't Hoff i factor can be determined and the value
compared with that computed from cryoscopic data, osmotic coefficient, and
activity coefficient.