LESSON 10 Methods of - PowerPoint Presentation

Slide1

LESSON 10

Methods

of

adjusting

Tonicity

and

pH

Several methods are used to adjust the isotonicity of

pharmaceutical solutions. Isotonicity can be calculated

from the

colligative

properties

of

drug solutions. If

solutions

are

injected

or

introduced

in

to

eyes

and

nose, these are to be made isotonic in order to avoid

haemolysis

of

RBC’s

and

to

avoid

pain

and

discomfort. This is possible for either manufactured or

extemporaneous

prepared

solutions.

By

using

the

appropriate

calculations

based

on

colligative

properties

of

solutions,

it

is

easy

to

determine

the

amount of adjusting agents to be added. It helps to

overcome the side effects caused from administering

solutions which contain adjusting agents less or more

than

isotonic

solutions.

The

three

frequently

used

methods to calculate isotonicity of the solutions are

described

below.

Class-1 Methods:

Nacl

or some other substances is

added to the solution of the drug to lower the freezing

point

of the

solution to

-0.52ᵒC and thus

make

the

solution isotonic.

Examples

of

this class-

Cryoscopic

method

Sodium

chloride

equivalent

method.

Class-2 Methods:

Water is added to the drug in a

sufficient

amount

to

make

it

isotonic.

Then

the

preparation

is

brought

to

its

final

volume

with

an

isotonic

or

buffered

isotonic solution.

Class I Methods:

Cryoscopic

method-

Isotonic solutions may be made in terms of data relating to colligative properties of solutions. Colligative properties include osmotic pressure, elevation in boiling point, depression in freezing point, and lowering of

vapour

pressure. Depression in freezing point is a colligative property which is practical and most convenient for adjusting tonicity. The freezing point of human blood and lacrimal fluids is – 0.52°C. This temperature corresponds to freezing point of 0.90% (w/v) sodium chloride solution. This is considered to be isotonic to blood and lacrimal fluids. The freezing point depression of 1% (w/v) sodium chloride (∆Tf1%) is 0.58°C. In this method, an amount of tonicity adjuster (e.g. sodium chloride) is added to drug solution such that the final freezing point lowering is that of blood or serum (0.52°C).

Sodium chloride equivalent method-

This method is based on calculating the E-value, i.e. the sodium chloride equivalent or tonicity equivalent of a drug. It is the amount of sodium chloride that has the same osmotic effect (i.e. is equivalent to) as 1 g of the drug.

Derivation of E-value:

 Since freezing point depression is a colligative property, it depends on the number of particles, dissociation and association of particles.

Therefore, the equation ∆

T

f

 =

K

f

C

can be replaced with ∆

T

f

 =

L

iso

C

where, ∆T is the depression in freezing point,

Kf

is the freezing point depression constant, c is the concentration.

Liso

is a factor that is equal to

iKf

, where

i

is the

vant

Hoff factor.

L

iso

= ∆

T

f

 / C

Class II Methods:

White–Vincent method-

The Class II methods of computing tonicity involve the addition of water to the drugs to prepare an isotonic solution, followed by the addition of an isotonic or isotonic-buffered diluting vehicle to make up the solution up to the final volume. White and Vincent developed a simplified method for performing such calculations. The equation is derived as shown below:

To prepare 30 mL of a 1% (w/v) solution of procaine hydrochloride isotonic with body fluid (=0.3 g), weight of the drug w is multiplied by the sodium chloride equivalent E.

This is the quantity of sodium chloride osmotically equivalent to 0.3 g of procaine hydrochloride

= weight of drug (g) × E of drug                                                                                           (1)

= 0.3 × 0.21 = 0.063 g

It is known that 0.9 g of sodium chloride when dissolved in sufficient water sufficient to make a final volume of 100 mL yields an isotonic solution. The volume V of isotonic solution that can be prepared from 0.063 g of sodium chloride (equivalent to 0.3 g of procaine hydrochloride) is obtained by solving the following proportion:

0.9g / 100ml = 0.063g / V

V = 0.063 X 100 / 0.9 = 7.0ml                                                                                              (2)

Accordingly, Eq. (2) can be written as

V = w × E × 111.1                                                                                                               (3)

where V is the volume of isotonic solution (in mL) that may be prepared by mixing the drug with water, w the weight of the drug (in grams) and E the sodium chloride equivalent of the drug. The constant, 111.1, represents the volume of isotonic solution in

millilitres

obtained by dissolving 1 g of sodium chloride in water.

The isotonic and isotonic-buffered diluting solutions all have isotonicity values of 0.9% NaCl.

Sprowls

method-

A further simplification of the method of White and Vincent was prepared by

Sprowls

. He recognized that the Eq. (3) given by White and Vincent could be utilized to make a table of values of V when the weight of the drug w was arbitrarily fixed.

Sprowls

chose 0.3 g as the weight of drug, the quantity for one fluid ounce of a 1% solution. The volume V of isotonic solution that can be prepared by mixing 0.3 g of a drug with sufficient water may be computed for drugs commonly formulate as ophthalmic and parenteral solutions.

The quantity of isotonic solution is finally brought to the specific volume with the desired isotonic or isotonic-buffered diluting solutions.