colligative property) is more cas1ly other
substances
methods : In this type, sodiun chloride or isotonic. Then
Class I make it
are added to the solution in suficicnt quantity towith an
isotonic or
preparation is brought to its final voume
the
buffered isotonic diluting solution.
types: Cryoscopic method method
These methods are of two
Sodivmchloride cquivalent
added in sufficient quantity
water is brought to its
Class Il methods : In this typc, the preparation is
make the preparation isotonic. Then
buffercd isotonic diluting solution.
to isotonic or a
final volume with an White-Vincent method
are of two types:
These methods Sprowls method
equivalent methods are discussed
Cryoscopic and sodium chloride
below.
Tonicity
Cryoscopic Method of Adjusting the point of 0 °C. Blood contains a
Water has the
Principle : freezing
as carbonic acid, carbonates, salts of phos
number of substances such the depression in the freezing
hemoglobin. As a result,
phoric acid and °C.
point of the blood is -0.52
substances such as sodium chloride are added to water, the
When
point of water decreases. The extent of depression in the
freezing
the added substance. For
freezing point depends on the concentration of decreases the freezing
example, sodium chloride at 1% w/y solution solution isotonic, the
point of water to -0.58°. In order to make the drug
at -0.52°.
freezing point depression of the solution must be maintained
TABLE 16-1
Freezing Point Depression* (AT) and
EValves of Some Drugs and Added Substances
Solution, 1% w/v drug 4T,,°C E
0.14
Apomorphine hydrochloride 0.08
Boric acid 0.29 0.50
Calcium gluconate 0.09 0.16
Pilocarpine nitrate 0.14 0.23
Potassium chloride 0.45 0.76
Sodium chloride 0.58 1.00
Sodium sulphacetamide 0.14 0.23
* Freezing point of water is 0
°C. *The negative signs are not included.
lnitiay the drug soution is preparcd whose depression in the freez
ing point (AT) is known. The remaining (AT) value is adjusted by
adding additional substances such as sodium chloride.
FOr the Purpose of calculations, the freezing point depressions of a
Mumber of drugs are
entration of 1.0% determincd experimentally or theoretically at con-
Table 16-1.
w/v (or soetimes 0.5% w/v). These are reported
Similarly the freczing point
i w/v solution of sodiunm chloride and other depression values of
gencral ingredients are
o determined and reported in the Table 16-1.
perivation : Freezing point depression (AT) of blood = 0.52°. Since
drug solution must be isotonic, it must have AT; same as that of the
Nood, i.e., AT;=0.520.
AT = AT;of drug +4T;of the
Total drug solution T;
adusting substance ...(1)
Freezing point depression (AT) of the total drug solution =0.52°
AT; value of the drug =xx AT; of 1% drug solution=d
shere x = drug concentration in the preparation, g/100 mL
AT, for adjusting solution = wxa
there w= weight of the adjusting substance, g/100 mL
a= AT;of the adjusting substance (sodium chloride), 1% (= 0.58)
For an isotonic solution, equation (1) is substituted by the terms
nentioned above.
0.52° d+ wa
The %w/v of adjusting substance needed is:
(0.52 - d) (0.52 - d)
W= ...2)
0.58
bquation (2) is valid, if 1% drug solution is specified. For any given
aCentage strength of medicamnent (PSM), equation (2) may be modified
0.52 -(PSM x d) ...3)
W=
0.58
Thus, the desired concentration of adjusting substance is calculated
added in order to make the drug preparation isotonic with blood.
Rh solute exerts its effect on the freezing point, although others are
Sent. Hence, if two or more substances are present, asum of their
ing point depressions should be considered.
