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part 1:
Isotonic Solutions
University of the Philippines- Manila
Industrial Pharmacy 121
Parenteral Products
sterile preparations
that are intended for
use by injection under
or through one or
more layers of the
skin or mucous
membrane
Requirements of Parenterals
Products
Sterility
Absence of Pyrogens (fever causing
agents)
Absence of Particulate Matter
Isotonicity
pH
Osmosis
2 solutions of different concentrations are
separated by a semi-permeable membrane
(only permeable to the solvent) the solvent
will move from the solution of lower conc. to
that of higher conc.
Osmotic pressure
is the pressure that must be applied to the
solution to prevent the passage of the solvent
through a perfect semipermeable membrane.
Osmotic Pressure
pressure responsible for the movement of
the solvent through a semipermeable
membrane
Osmotic pressure
Colligative property
Depends on the number of particles in the
solution
Substance that dossociate has greater
number of particles and therefore greater
osmotic pressure
Nonelectrolytes
dissolve as
molecules in water
do not produce ions
in water
Osmotic pressure will
vary only due to
concentration of
solute
10
Weak Electrolytes
A weak electrolyte
dissociates only slightly in water
in water forms a solution of a few ions
and mostly undissociated molecules
11
Strong Electrolytes
Strong electrolytes
dissociate in water, producing positive
and negative ions
OP will vary not only in concentration
but also in degree of dissociation
12
Classification of Solutes in
Aqueous Solutions
13
Isosmotic
solutions having the same osmotic
pressure
required of solutions intended to be mixed
with body fluids
for greater comfort , efficacy, and safety
Isotonic
Isotonic
same osmotic pressure as a specific body fluid (equal
tone with that body fluid)
Blood and the body fluids of the eye, nose and bowel
Products which require the same tonicity biologic
fluids: ophthalmic, nasal, parenteral and some rectal
preparations
Hypertonic
higher osmotic pressure than that of the body fluid
Fate of cells
METHODS TO MAKE
SOLUTIONS ISOTONIC
Example
1. What is the dissociation factor of NaCl,
having 80% dissociation in water? Assume
that we have 100 particles of NaCl prior to
dissociation.
Example
What is the dissociation factor of zinc
chloride, having 80% dissociation in
water? Assume that we have 100 particles
of zinc chloride prior to dissociation.
Answer
Dissociation Factors
Nonelectrolytes and substances of slight
dissociation ; 1.0
Substances that dissociate into 2 ions;
1.8
Substances that dissociate into 3 ions;
2.6
Substances that dissociate into 4 ions;
3.4
Substances that dissociate into 5 ions;
4.2
Example
Calculate the sodium chloride equivalent
of a 1% solution of pilocarpinenitrate.
Pilocarpinenitrate has a molecular weight
of 271 and i of 1.8
Example 2
Calculate the sodium chloride equivalent
of a 1% boric acid. Boric acid has a
molecular weight of 62 and i of 1
ISOTONICITY ADJUSTMENTS
BY NaCl EQUIVALENT
most frequently used method in the
calculation of the amount of sodium
chloride needed to prepare isotonic drug
solutions.
Step 1
how much sodium chloride is needed to
render the formulation isotonic with body
fluids.
(Remember isotonicity refers to 0.9% or
0.9 g/100 mL).
Step 2
Find the amount of sodium chloride
represented by the ingredients in the
prescription by multiplying the quantity of
each ingredient by its E value.
Add up all the values obtained. This is the
total amount of sodium chloride
represented by all the ingredients in the
prescription
Step 2
The sodium chloride equivalent of atropine
sulfate is 0.13 .
This means that 1% solution of atropine
sulfate has same osmotic pressure as that
of 0.13% solution of sodium chloride.
This solution is hypotonic.
Step 3
Subtract the total value obtained in Step 2
from the amount of sodium chloride
required to render the formulation isotonic
The value obtained in this step represents
the amount of sodium chloride required to
render the solution isotonic.
Step 3
0.9 0.13 = 0.77 of sodium chloride per
100 mL of the 1% solution of atropine
sulfate results in an isotonic solution.
Final answer: Addition of 0.77 g
ISOTONICITY ADJUSTMENTS
BY CRYOSCOPIC METHOD
The normal freezing (or melting)point of a
pure compound is the temperature at
which the solid and the liquidphases are in
equilibrium at a pressure of 1 atm.
Pure water has a freezing point of 0C.
When solutes are added to water, its
freezing point is lowered.
Cryoscopic Method
Example
Compound the prescription
Steps
Step 1:Find the value of freezing point
depression of the drug at 1%concentration
Step 2:
Subtract T1% f of the drug from the value of
freezing point. depression of 0.9% sodium
chloride solution, i.e., 0.52.
This difference may be symbolized as Tf,
which is the freezing point lowering
needed for isotonicity.
Step 2 of example
0.52 0.07 = 0.45.
This means, sufficient sodium chloride
must be added to lower the freezing point
by an additional 0.45
Step 3 of example
Find the percentage concentration of
sodium chloride required by setting up the
proportion as follows:
Sample Proble
How many milligrams each of NaCl and dibucaine
HCl are required to prepare 30 mL of 1%
solution of dibucaine HCl isotonic with tears?
To make the solution isotonic , the freezing point
must be lowered to 0.52oC
A 1% solution of dibucaine HCl has a freezing
point lowering of 0.08oC
Step 3
1% (NaCl)
--------------x % (NaCl)
x =
0.58oC
----------0.44oC
0.76%
White-Vincent Method
provided a method for readily finding the
correct volume of water in which to
dissolve a drug to produce a solution isoosmotic with tears.
followed by the addition of an isotonic
vehicle to bring the solution to the final
volume.
Formula
END