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Objectives

OUR LADY OF FATIMA UNIVERSITY  To determine the significance of water content

determination in analysis of pharmaceutical
COLLEGE OF PHARMACY ingredients and products.
QUALITY CONTROL  To identify the different techniques in water content
determination used in analysis of pharmaceutical
(QC325) products and ingredients.

WATER CONTENT DETERMINATION

WEEK 14

Moisture Determination Water content is determined for the

following reasons:
 Official Drugs vary in their water content. Water  When crude drugs are sold with a guaranteed
available either as water of crystallization assay for active constituent. The percent active
(hydrates) or as water in the adsorbed form. constituent must be calculated on the basis of the
 Determination of this constant is necessary to moisture-free drug .
specify certain water content limits in the drug  In scientific work, moisture or water content of crude
monographs. drugs and other substances must be accurately
 In order to ensure uniformity in the official drugs determined since variable quantities of moisture
would adversely affect the calculated results .

Water content is determined by any

one of the six methods:
 Most official chemical compounds are relatively 1. Gravimetric Method – for drugs containing no
stable with respect to their moisture content at room constituents other than water, volatile at 105 C.
temperature. Some of them are hygroscopic and 2. Gravimetric Method – for drugs containing ether-
absorb water readily. Others lose part or all of soluble constituents, volatile at 105 C.
their water of crystallization.  Control of the 3. Azeotropic Method or toluene distillation - for the
amount of water contained in chemicals is determination of moisture content of many
important in making solution of definite vegetable drugs containing 2% or more of moisture
concentration and in the determination of the
dosage substances used as medicaments.

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Water content is determined by any Water Content Determination Official

one of the six methods: Methods
4. Titrimetric Method or Karl Fischer Method - for METHOD I. Titrimetric Method/ Karl-Fischer
crystalline compounds that contain water of Method
hydration or absorbed water
Ia – direct Titration
5. Dew Point Method – for determining Water at
Very Low Concentration Ib – Residual titration
6. Electrolytic Hygrometric – for determining Ic - Coulomteric titration
Extremely Low Concentration of Water  “1 mL of of the reagent is equivalent to

approximately 5 milligrams of water”

Water Content Determination Official

Method I - Karl Fischer method
Methods
METHOD II. Azeotropic Method/ Distillation Method  This method is the most rapid, requires only a small
METHOD III. Gravimetric Method/ Drying/Thermal sample and is specific for water.
Method  The method involves titration of the sample in
 Method of choice for chemical samples (1-2 grams), reagent methanol with Karl Fischer reagent, which
vegetable drugs and biologics consists of iodine, sulfur dioxide, pyridine, and
methanol.

Contents of KFR

Anhydrous Prevents the

 The Karl Fischer reagent has a concentration such
pyridine-sulfur
methanol complex that one mL of the reagent is equivalent to
HYDROIODIC ACID approximately five milligrams of water. (1 ml = 5
Iodine React with water
mg of water)
Sulfur dioxide  The reagent deteriorates gradually; it is
SULFUR TRIOXIDE
standardized by employing sodium tartrate
Prevents reverse (Na2C4H4O6.2H2O) as a primary standard.
Pyridine reaction

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Procedure for the Standardization of

Karl Fischer Reagent:
   The water equivalence (F) mg of water per mL of the
reagent is given by the formula
 Place 36 mL of methanol in the titration vessel and 0.1566 X W
add sufficient Karl Fischer reagent to give the V
characteristic endpoint (canary yellow color).  Where W is the weight in mg of sodium tartrate and V
Quickly add 150 to 350 mg of an accurately is the volume in mL of the reagent required . Each mg of
sodium tartrate is equivalent to
weighed sodium tartrate and titrate to the endpoint.
2H2O 36.04
wt of water = -------------------------- = ---------------------
-
Na 2C4H4O6 . 2H 2O 230.08

General Procedure for Water Determination

using the Titrimetric Method: Method II – Azeotropic Method
 Add about 25 mL of methanol to the titration flask  The Azeotropic Method is specified for the
and titrate to the endpoint with Karl Fischer reagent determination of moisture content of many
disregarding the volume consumed. Weigh or vegetable drugs containing 2% or more of moisture.
measure sufficient sample to contain preferably 10
to 50 mg of water and quickly transfer it to the  Its disadvantage is the need for a large amount if
titration flask. Stir and titrate with Karl Fischer drug, from fifty (50) to one hundred (100) grams
reagent. must be used in order to secure a volume of water
 The water content of the sample in mg SxF; that can be measured conveniently without
where S is the volume of the reagent used to titrate considerable error.
and sample F is the water equivalence factor.

Determination of the Moisture Content of Determination of the Moisture Content of

Digitalis by the Toluene Distillation Method Digitalis by the Toluene Distillation Method

 Accurately weigh a quantity of the drug which is  Heat the flask gently for fifteen minutes and when the
toluene begins to boil, distill at the rate of two (2) drops
estimated to yield two to four mL of water and per second until most of the water has passed over, then
place it in the dry flask. increase the rate of distillation to about four (4) drops
per second.
 Place about 200 mL of toluene in the flask, connect
 When the water has distilled over, rinse the condenser
the apparatus and fill the receiving tube with tube with toluene. Continue the distillation for five
toluene poured through the top of the condenser. minutes, remove the heat and allow the receiving tube to
cool to room temperature.
 When the water and toluene have separated
completely, read the volume of the water and calculate
the percent of moisture in the sample.

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Determination of the Water Content of Acacia

Method III - Gravimetric method by the Gravimetric Method

 When the drug contains matter other than water  Accurately weigh about ten (10) grams of the drug
which is volatile at 105 C, the volatile ether soluble in a tared evaporating dish. Dry at 105 C for five
extractive must be determined and the weight of (5) hours and weigh. Continue drying and weighing
this extractive is subtracted from the weight less by at one (1) hour interval until the loss in weight is not
more than 0.25% in one (1) hour drying. The
the drug upon drying, the difference is the moisture
moisture and any other volatile constituents of
content of the drug. acacia are driven off.

Q: Calculate the percent of moisture in the sample of

acacia if the final weight is 8.78 grams.

Dew Point Method for Determining

Electrolytic Hygrometric Method
Water at Very Low Concentration:
 The amount of water vapor in a system may be  Determining Extremely Low Concentration of Water:
determined by noting the temperature at which a  The principle of selective electrolysis of water may
dew or mist forms when the system is suddenly be employed and the amount of electric current is a
cooled under adiabatic expansion following release measure of the water content.
of compression. Water content is determined by
reference to calibrated charts.

Formula Used in Moisture Content

Determinations Sample problem
1. Moisture content of citric acid was determined by the Karl-
fischer Method and the following data were obtained
 Weight of Moisture wt of citric acid …………………………4.8 g
vol of reagent used ……………………20 ml
 Weight before drying– Weight after drying
 % Moisture Content water equivalence factor of the reagent was determined by
 % = Weight of moisture x 100% titrating 0.350g of sodium tartrate with 10 ml of KFR,
determine the water content of citric acid
Weight of sample
 % Moisture Content

% = Weight before – Weight after x100%

Weight before drying

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Sample problem Sample problem

2. Weight of the powdered digitalis leaves …………48.645 g 3. From the assay of sodium citrate sample using karl
vol. of water collected water from the distillate…. …. 2.5 ml fischer method, the following results were obtained:
USP, water limits is 2% Wt of sample 3.65 g sample
Vol of titrant 20 ml
1. compute for the percent of moisture present in the Wt of primary standard 235 mg
sample Vol consumed during titration 7.46 ml
2. if exactly 50 g of digitalis was weighed, what a. determine the amount of water in mg
would be the volume of water collected if the b. determine the water equivalence factor
percentage is 6% c. compute for % water

Sample problem Sample problem

4. A crude drug weighing 10.0525g was 5. If an air-dried drug containing 10%

dried in an oven for several hours moisture yielded 2.5% ash calculated on
yielding a residue equivalent to 3.6572g. the basis of the air-dried drug, what
Calculate the weight loss on drying and percent of ash would the moisture-free
the % moisture content. drug contain?

END OF WEEK 14

THANK YOU!
PLEASE ANSWER THE ACTIVITY FOR WEEK 14