Parenteral Solution

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

Hypotonic and Hypertonic

Hypotonic
lower osmotic pressure than that of the body fluid

Hypertonic
higher osmotic pressure than that of the body fluid

Fate of cells

Clinical Consideration of Tonicity

Ophthalmic and Parenteral preparation
-Isotonic
Edematous tissues
- Hypertonic
Dehydration
- Hypotonic

METHODS TO MAKE
SOLUTIONS ISOTONIC

Method I: NaCl Equivalent

Step 1: CALCULATION OF DISSOCIATION
(i) FACTOR
Since osmotic pressure depends upon the
number of particles of solute(s) in solution,
the osmotic pressure of an electrolyte is
directly proportional to the degree (or
extent) of dissociation.

Calculation of dissociation factor

(i)

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.

Since strong electrolyte

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

Step 2: Know the

Sodium Chloride Equivalent
The sodium chloride equivalent of a
chemical is defined as the amount of
sodium chloride (in grams or grains) that
has the same osmotic pressure as that of
1 g of the chemical.

Sodium Chloride Equivalent of

Substance

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.

Fill the Prescription

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

TONICITY AGENTS OTHER

THAN SODIUM CHLORIDE
such as dextrose or boric acid
A proportion can be set up which can be
treated as Step 4 in addition to the three
steps described earlier
the quantity of that chemical can be
calculated by dividing the amount of
sodium chloride needed (step 3) with the
E value of that chemical.

 Find the quantity of boric acid (in grams)

to be used in compounding the following
prescription. Boric acid E value= 0.52

 Find the quantity of boric acid (in grams)

to be used in compounding the following
prescription. But instead of Boric acid use
dextrose with E= 0.16

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.

The freezing point depression

dependent only on the number of particles
in the solution.
Blood plasma has a freezing point of
0.52 {or freezing point depression of
0.52, i.e., ( [0.52])}.

Cryoscopic Method

 1% NaCl has a freezing point of 0.576 c.

What is the percentage concentration of
NaCl required to make isotonic saline
solution?

 Drug solutions which have a freezing point

depression of 0.52 are, therefore, isotonic
with blood.
A list of freezing point depression values
of selected compounds at 1%
concentration .

 Tf values may be used to calculate the

concentration of tonicity agents, such as
sodium chloride or boric acid, needed to
render a hypotonic drug solution isotonic
with blood plasma.

Example
Compound the prescription

Steps
Step 1:Find the value of freezing point
depression of the drug at 1%concentration

Based on the example

Freezing point depression (Tf) of 1%
atropine solution is 0.07.

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:Since 0.9% sodium chloride has a

freezing point depression of 0.52, one can
calculate the percentage concentration of
sodium chloride required to lower the
difference in freezing points, i.e., the value
obtained.in Step 2, _Tf, by the method of
proportion.

Step 3 of example
Find the percentage concentration of
sodium chloride required by setting up the
proportion as follows:

 It is observed that 1% solution of sodium

chloride has a freezing point lowering of
0.58. Therefore, one can also express the
proportion as:

solving for X, we get: (0.45/0.58) 1 =

0.78%

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 1: A 1% solution of dibucaine HCl

has a freezing point lowering of 0.08 oC
Step 2: Thus freezing point must be
lowered by an additional of 0.52 oC
0.08oC = 0.44oC by addition of more NaCl

Step 3
1% (NaCl)
--------------x % (NaCl)
x =

0.58oC
----------0.44oC

0.76%

To make the 30 mL solution,

30 mL x 1% = 0.3 g or 300 mg dibucaine HCl
30 mL x 0.76% = 0.228 g or 228 mg NaCl

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

 If more than one ingredient is contained in

an isotonic preparation, the volume of
isotonic solution obtained by mixing each
drug with water are additive.

 E value of procaine HCl = 0.21

 The weight of procaine HCl

= (1/100) x 60 = 0.6g
The volume of isotonic solution that can
be prepared with drug

 In order to make the solution isotonic the

three ingridients should be dissolved in
54.3mL of water and the preparation is
adjusted to 60mL using an isotonic
vehicle.

END