FORMULATION OF ALOE VERA COSMETIC HERBAL

HYDROGEL

ABSTRACT
Present study deals with the development and characterization of aloe vera cosmetic herbal
hydrogel preparation using inner part of aloe vera leaf, acacia, hydroxy propyl methyl cellulose
(HPMC), carbopol 934, glycerine, tartaric acid, potassium sorbate and sodium benzoate. Aloe
vera liquid was prepared by heating at low temperature and the hydrogel was prepared by simple
dissolving method of other ingredients in a specific manner. Four formulations were developed
which differ in the ratio of hydrogel forming polymers. Formulation A1, A2, A3 and A4 were
composed of acacia, HPMC, carbopol 934 in the ratio of 1:1:1, 1:2:1, 2:1:1 and 1:1:2
respectively. All the formulations were evaluated for percentage moisture content, transparency.

INTRODUCTION
Aloe vera is an important medicinal plant. It has larger demands and is traded in medicinal drug
markets of the world for flavouring liquid and a source of aloin (4.5 to 25 per cent). In more
traditional uses, physicians use aloe vera-based creams to heal serious thermal injuries, such as
burns and frostbite. Dentists employ aloe vera gels to reduce swelling and inflammation of the
gums. Dermatologists rely on aloe vera products to help clear acne, and optometrists find the
products helpful in soothing eye inflammations. Professional sports trainers treat their athletes
muscle aches and sprains, skin abrasions, and blisters with aloe vera. Cosmetics companies, for
its beneficial effect of aloe Vera, incorporate it into, cosmetic and skin care products. It is also for
the marketing appeal the words made with aloe attract the consumer. Drinking aloe vera with
honey is said to have the therapeutic effects on arthritis, ulcers, diabetes, and other health
conditions. The wide range of applications, and the beneficial effects of its use, continues to
increase the popularity of this ancient plant.Aloevera is a perennial, drought-resisting, succulent
plant belonging to the Lily (Liliaceae) family which, historically, has been used for a variety of
medicinal purposes. The plant has stiff grey-green lanceshaped leaves containing clear gel in a
central mucilaginous pulp. Clinical evaluations have revealed that the pharmacological active
ingredients are concentrated in both the gel and rind of the aloe vera leaves. These active
ingredients have been shown to have analgesic and anti-inflammatory effects. The true aloe vera
plant is called Aloe barbadensis Miller, otherwise called the Curacao aloe, and is the most
medicinally potent of the 300 (and more) varieties found around the world. Most people in the
UK today know of aloe vera because of its inclusion in many popular cosmetic products. Over
the years, the plant has been known by a number of names such as the wand of heaven,
heavens blessing and the silent healer.Number of aloe vera herbal formulations available in
the form of cream, gel, facial solution, moisturizer etc, while these formulations contain very less
quantity of aloe vera extract and herbal component. These formulations may also contain toxic
ingredients such as surfactant. Present investigation deals with the development of aloe vera
cosmetic

Master formula
Table 1: Composition of aloe vera herbal hydrogel formulations A1 to A4
Ingredients
Aleovera ml

A1
75

Acacia gm

A2

A3

75

0.5

A4

75

0.375

75

0.375 0.75

HPMC gm

0.5 0.75

0.375

Carbopol 934 gm

0.5 0.375 0.375

Glycerine ml

0.375
0.75
5

Ascorbic acid
Albumin
Tartaric acid gm

1.5

Potassium sorbate gm 0.5

Sodium benzoate gm

1.5
0.5

1.5

1.5

0.5 0.5

0.5 0.5 0.5

Double distilled water q.s up to 100 ml

0.5

Preparation of aloe vera herbal gel

An aloe vera gel is converted into liquid form by heating at a low temperature for two hours. It is
necessary that it should be heated at a low temperature in order to retain thermo sensitive
ingredients present in it. Tartaric acid is added to the aloe vera concentrate to adjust the pH
within the range from 5.5 to 6.0. In separate container, the hydrogel forming polymers were
dissolved in small amount of double distilled water in various proportions as shown in Table
no.1, and then remaining ingredients i.e. glycerin, potassium sorbate and sodium benzoate were
added. Now, aloe vera liquid extract was added to it and make up the volume up to 100 ml. The
pH of this gel preparation was maintained 60.4 and stored in a well closed container.
Aloe vera gel

Hydrogel forming polymers

+

Heating

Double distilled water

Liquid concentrate
+

glycerin, potassium

sorbate ,
Tartaric acid

Both solution are mixed and make a volume up to 100 ml

sodium benzoate add

MONOGRAPHS

Acacia
DEFINITION
Air-hardened, gummy exudate flowing naturally from or obtained by incision of the trunk and branches of Acacia.
CHARACTERS
Acacia is almost completely but very slowly soluble, after about 2 h, in twice its mass of water leaving only a very small
residue of vegetable particles; the liquid obtained is colourless or yellowish, dense, viscous, adhesive, translucent and weakly
acid to blue litmus paper. Acacia is practically insoluble in ethanol (96 percent).
IDENTIFICATIOn
A. Acacia occurs as yellowish-white, yellow or pale amber, sometimes with a pinkish tint, friable, opaque, spheroidal, oval or
reniform pieces (tears) of a diameter from about 1-3 cm, frequently with a cracked surface, easily broken into irregular, whitish
or slightly yellowish angular fragments with conchoidal fracture and a glassy and transparent appearance. In the centre of an
unbroken tear there is sometimes a small cavity.
B. Reduce to a powder (355) (2.9.12). The powder is white or yellowish-white. Examine under a microscope using a 50 per cent
V/V solution of glycerol R. The powder shows the following diagnostic characters: angular, irregular, colourless, transparent
fragments. Only traces of starch or vegetable tissues are visible. No stratified membrane is apparent.
TESTS
Solutions
Dissolve 3.0 g of the powdered drug (355) (2.9.12) in 25 mL of water R by stirring for 30 min. Allow to stand for 30 min and
dilute to 30 mL with water R.
Insoluble matter
Maximum 0.5 per cent.
To 5.0 g of the powdered drug (355) (2.9.12) add 100 mL of water R and 14 mL of dilute hydrochloric acid R, boil gently for 15
min, shaking frequently and filter while hot through a tared sintered-glass filter (2.1.2). Wash with hot water R and dry at 100105 C. The residue weighs a maximum of 25 mg.
Glucose and fructose
Thin-layer chromatography (2.2.27).
Test solutionTo 0.100 g of the powdered drug (355) (2.9.12) in a thick-walled centrifuge tube add 2 mL of a 100 g/L solution
of trifluoroacetic acid R, shake vigorously to dissolve the forming gel, stopper the tube and heat the mixture at 120 C for 1 h.
Centrifuge the hydrolysate, transfer the clear supernatant carefully into a 50 mL flask, add 10 mL of water R and evaporate the
solution to dryness under reduced pressure. To the resulting clear film add 0.1 mL of water R and 0.9 mL of methanol R.
Centrifuge to separate the amorphous precipitate. Dilute the supernatant, if necessary, to 1 mL with methanol R.
Reference solution:
Dissolve 10 mg of arabinose R, 10 mg of galactose R, 10 mg of glucose R, 10 mg of rhamnose R and 10 mg of xylose R in 1 mL
of water R and dilute to 10 mL with methanol R.

Ascorbic acid
DEFINITION
(5R)-5-[(1S)-1,2-Dihydroxyethyl]-3,4-dihydroxyfuran-2(5H)-one.
Content
99.0 per cent to 100.5 per cent.
CHARACTERS
Appearance
White or almost white, crystalline powder or colourless crystals, becoming discoloured on exposure to air and moisture.
Solubility
Freely soluble in water, sparingly soluble in ethanol (96 per cent).
MP
About 190 C, with decomposition.
IDENTIFICATION
First identificationB, C.
Second identificationA, C, D
A. Ultraviolet and visible absorption spectrophotometry (2.2.25).
Test solutionDissolve 0.10 g in water R and dilute immediately to 100.0 mL with the same solvent. Add 1.0 mL of this solution to 10 mL of
0.1 M hydrochloric acid and dilute to 100.0 mL with water R.
Absorption maximumAt 243 nm, determined immediately after dissolution.
Specific absorbance at the absorption maximum545 to 585.
B. Infrared absorption spectrophotometry (2.2.24).
Comparisonascorbic acid CRS.
C. pH (2.2.3): 2.1 to 2.6 for solution S (see Tests).
D. To 1 mL of solution S add 0.2 mL of dilute nitric acid R and 0.2 mL of silver nitrate solution R2. A grey precipitate is formed.
TESTS
Solution S
Dissolve 1.0 g in carbon dioxide-free water R and dilute to 20 mL with the same solvent.
Appearance of solution
Solution S is clear (2.2.1) and not more intensely coloured than reference solution BY7 (2.2.2, Method II).
Specific optical rotation (2.2.7) + 20.5 to + 21.5.
Dissolve 2.50 g in water R and dilute to 25.0 mL with the same solvent.
Impurity E
Maximum 0.2 per cent.
Test solutionDissolve 0.25 g in 5 mL of water R. Neutralise using dilute sodium hydroxide solution R and add 1 mL of dilute acetic acid R and
0.5 mL of calcium chloride solution R.
Reference solutionDissolve 70 mg of oxalic acid R in water R and dilute to 500 mL with the same solvent; to 5 mL of this solution add 1 mL
of dilute acetic acid R and 0.5 mL of calcium chloride solution R.
Allow the solutions to stand for 1 h. Any opalescence in the test solution is not more intense than that in the reference solution.
Related substances

Tartaric acid
DEFINITION
(2R,3R)-2,3-Dihydroxybutanedioic acid.
Content
99.5 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance
White or almost white, crystalline powder or colourless crystals.
Solubility
Very soluble in water, freely soluble in ethanol (96 per cent).
IDENTIFICATION
A. Solution S (see Tests) is strongly acid (2.2.4).
B. It gives the reactions of tartrates (2.3.1).
TESTS
Solution S
Dissolve 5.0 g in distilled water R and dilute to 50 mL with the same solvent.
Appearance of solution
Solution S is clear (2.2.1) and not more intensely coloured than reference solution Y6 (2.2.2, Method II).
Specific optical rotation (2.2.7)
+ 12.0 to + 12.8 (dried substance).
Dissolve 5.00 g in water R and dilute to 25.0 mL with the same solvent.
ASSAY
Dissolve 0.650 g in 25 mL of water R. Titrate with 1 M sodium hydroxide using 0.5 mL of phenolphthalein solution R as indicator, until a pink
colour is obtained.
1 mL of 1 M sodium hydroxide is equivalent to 75.05 mg of C4H6O6.

Potassium sorbate gum

DEFINITION
Potassium (E,E)-hexa-2,4-dienoate.
Content
99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance
White or almost white powder or granules.
Solubility
Very soluble in water, slightly soluble in ethanol (96 per cent).
IDENTIFICATION
First identificationB, D.
Second identificationA, C, D.
A. Ultraviolet and visible absorption spectrophotometry (2.2.25).
Test solutionDissolve 50.0 mg in water R and dilute to 250.0 mL with the same solvent. Dilute 2.0 mL of this solution to 200.0 mL with 0.1 M
hydrochloric acid .
Spectral range230-350 nm.
Absorption maximumAt 264 nm.
Specific absorbance at the absorption maximum1650 to 1900.
B. Infrared absorption spectrophotometry (2.2.24).
Comparisonpotassium sorbate CRS.
TESTS
Solution S
Dissolve 2.5 g in carbon dioxide-free water R and dilute to 50 mL with the same solvent.
Appearance of solution
Solution S is clear (2.2.1) and not more intensely coloured than reference solution Y5 (2.2.2, Method II).
Loss on drying (2.2.32)
Maximum 1.0 per cent, determined on 1.000 g by drying in an oven at 105 C for 3 h.
ASSAY
Dissolve 0.120 g in 20 mL of anhydrous acetic acid R. Titrate with 0.1 M perchloric acid using 0.1 mL of crystal violet solution R as indicator
until the colour changes from violet to bluish-green.
1 mL of 0.1 M perchloricacid is equivalent to 15.02 mg of C6H7KO2.

Sodium benzoate

DEFINITION
Sodium benzenecarboxylate.
Content
99.0 per cent to 100.5 per cent (dried substance).
CHARACTERS
Appearance
White or almost white, crystalline or granular powder or flakes, slightly hygroscopic.
Solubility
Freely soluble in water, sparingly soluble in ethanol (90 per cent V/V).
IDENTIFICATION
A. It gives reactions (b) and (c) of benzoates (2.3.1).
B. It gives reaction (a) of sodium (2.3.1).
TESTS
Solution S
Dissolve 10.0 g in carbon dioxide-free water R and dilute to 100 mL with the same solvent.
Appearance of solution
Solution S is clear (2.2.1) and not more intensely coloured than reference solution Y6 (2.2.2, Method II).
Acidity or alkalinity
To 10 mL of solution S add 10 mL of carbon dioxide-free water R and 0.2 mL of phenolphthalein solution R. Not more than 0.2 mL of 0.1 M
sodium hydroxide or 0.1 M hydrochloric acid is required to change the colour of the indicator.
Halogenated compounds
Maximum 200 ppm for ionised chlorine and maximum 300 ppm for total chlorine.
All glassware used must be chloride-free and may be prepared by soaking overnight in a 500 g/L solution of nitric acid R, rinsed with water R
and stored full of water R. It is recommended that glassware be reserved exclusively for this test.
Test solutionTo 20.0 mL of solution S add 5 mL of water R and dilute to 50.0 mL with ethanol (96 per cent) R.
Loss on drying (2.2.32)
Maximum 2.0 per cent, determined on 1.00 g by drying in an oven at 105 C.
ASSAY
Dissolve 0.250 g in 20 mL of anhydrous acetic acid R, heating to 50 C if necessary. Cool. Using 0.05 mL of naphtholbenzein solution R as
indicator, titrate with 0.1 M perchloric acid until a green colour is obtained.

Aloevera
Aloe is the dried latex of the leaves of Aloe barbadensis Miller (Aloe veraLinn), known in commerce as Curaao Aloe, or of Aloe ferox Miller
and hybrids of this species with Aloe africana Miller and Aloe spicata Baker, known in commerce as Cape Aloe (Fam. Liliaceae).
Identification
C: To 5 mL of the filtrate obtained in Identification test B add 2 mL of nitric acid: the mixture exhibits a reddish orange color with Curaao Aloe,
and a reddish brown color which changes rapidly to green with Cape Aloe.
Total ash
561
921
: not more than 4.0%.
: not more than 12.0%, determined by drying at 105
Cape Aloe Dusky to dark brown irregular masses, the surfaces of which are often covered with a yellowish powder. Its fracture is smooth and
glassy.
Powdered Aloe Yellow, yellowish brown to olive-brown in color. When mounted in a bland expressed oil, it appears as greenish yellow to
reddish brown angular or irregular fragments, the hues of which depend to some extent upon the thickness of the fragments.
A: Powdered Aloe dissolves in nitric acid with effervescence, forming a reddish brown to brown or green solution.
B: Intimately mix in a flask or bottle 1 g of finely powdered Aloe with 25 mL of cold water, shake the mixture occasionally during 2 hours,
transfer to a filter, and wash the filter and residue with sufficient cold water to make the filtrate measure 100 mL: the color of the filtrate, viewed
in the bulb of a 100-mL volumetric flask, is dark orange with Curaao Aloe, and greenish yellow with Cape Aloe. The filtrate darkens on
standing.
Assay
Macerate about 2 g of Aloe, accurately weighed, in about 70 mL of water in a suitable flask. Shake the mixture during 8 hours at 30-minute
intervals, and allow it to stand for 16 hours without shaking. Filter, and wash the flask and residue with small portions of water, passing the
washings through the filter, until the filtrate measures 100.0 mL. Evaporate a 50-mL aliquot of the filtrate in a tared dish on a steam bath to
dryness, and dry at 110 to constant weight. The weight of water-soluble extractive so obtained is not less than 50.0% of the weight of Aloe taken.

QUALITY CONTROL TESTS OF ALOEVERA GEL

MINIMUM FILL
The following tests and specifications apply to articles such as creams, gels, jellies, lotions,
ointments, pastes, powders, and aerosols, including pressurized and nonpressurized topical
sprays that are packaged in containers in which the labeled content is not more than 150 g or 150
mL.
PROCEDURE FOR DOSAGE FORMS OTHER THAN AEROSOLS For containers labeled
by weight, select a sample of 10 filled containers, and remove any labeling that might be altered
in weight during the removal of the container contents. Thoroughly cleanse and dry the outside
of the containers by a suitable means, and weigh individually. Quantitatively remove the contents
from each container, cutting the latter open and washing with a suitable solvent, if necessary,
taking care to retain the closure and other parts of each container. Dry, and again weigh each
empty container together with its corresponding parts. The difference between the two weights is
the net weight of the contents of the container. For containers labeled by volume, pour the
contents of 10 containers into 10 suitable graduated cylinders, and allow to drain completely.
Record the volume of the contents of each of the 10 containers. The average net content of the 10
containers is not less than the labeled amount, and the net content of any single container is not
less than 90% of the labeled amount where the labeled amount is 60 g or 60 mL or less, or not
less than 95% of the labeled amount where the labeled amount is more than 60 g or 60 mL but
not more than 150 g or 150 mL. If this requirement is not met, determine the content of 20
additional containers. The average content of the 30 containers is not less than the labeled
amount, and the net content of not more than 1 of the 30 containers is less than 90% of the
labeled amount where the labeled amount is 60 g or 60 mL or less, or less than 95% of the
labeled amount where the labeled amount is more than 60 g or 60 mL but not more than 150 g or
150 mL.

PACKEGING TEST
Containers Containers, including the closures, for ophthalmic ointments do not interact
physically or chemically with the preparation in any manner to alter the strength, quality, or
purity beyond the official requirements under the ordinary or customary conditions of handling,
shipment, storage, sale, and use.

Metal Particles Follow the Procedure set forth under Metal Particles in Ophthalmic
Ointments 751.
Leakage Select 10 tubes of the Ointment, with seals applied when specified. Thoroughly clean
and dry the exterior surfaces of each tube with an absorbent cloth. Place the tubes in a horizontal
position on a sheet of absorbent blotting paper in an oven maintained at a temperature of 60 3
for 8 hours. No significant leakage occurs during or at the completion of the test (disregard traces
of ointment presumed to originate externally from within the crimp of the tube or from the thread
of the cap). If leakage is observed from one, but not more than one, of the tubes, repeat the test
with 20 additional tubes of the Ointment. The requirement is met if no leakage is observed from
the first10 tubes tested, or if leakage is observed from not more than one of 30 tubes .
pH
pH = pHs + (E E S ) / k
BUFFER SOLUTIONS FOR STANDARDIZATION OF THE PH METER
Buffer Solutions for Standardization are to be prepared as directed in the accompanying table. *
Buffer salts of requisite purity can be obtained from the National Institute of Science.
For compendial purposes, pH is defined as the value given by a suitable, properly standardized,
potentiometric instrument (pH meter) capable of reproducing pH values to 0.02 pH unit using an
indicator electrode sensitive to hydrogen-ion activity, the glass electrode, and a suitable reference
electrode. The instrument should be capable of sensing the potential across the electrode pair
and, for pH standardization purposes, applying an adjustable potential to the circuit by
manipulation of standardization, zero, asymmetry, or calibration control, and should be
able to control the change in millivolts per unit change in pH reading through a temperature
and/or slope control. Measurements are made at 25 2, unless otherwise specified in the
individual monograph or herein.
in which E and E S are the measured potentials where the galvanic cell contains the solution
under test, represented by pH, and the appropriate Buffer Solution for Standardization,
represented by pHs, respectively. The value of k is the change in potential per unit change in pH
and is theoretically [0.05916 + 0.000198(t 25)] volts at any temperature t.
It should be emphasized that the definitions of pH, the pH scale, and the values assigned to the
Buffer Solutions for Standardization are for the purpose of establishing a practical, operational
system so that results may be compared between laboratories. The pH values thus measured do

not correspond exactly to those obtained by the definition, pH = log a H + . So long as the
solution being measured is sufficiently similar in composition to the buffer used for
standardization, the operational pH corresponds fairly closely to the theoretical pH. Although no
claim is made with respect to the suitability of the system for measuring hydrogen-ion activity or
concentration, the values obtained are closely related to the activity of the hydrogen-ion in
aqueous solutions.
Where a pH meter is standardized by use of an aqueous buffer and then used to measure the
pH of a nonaqueous solution or suspension, the ionization constant of the acid or base, the
dielectric constant of the medium, the liquid-junction potential (which may give rise to errors of
approximately 1 pH unit), and the hydrogen-ion response of the glass electrode are all changed.
For these reasons, the values so obtained with solutions that are only partially aqueous in
character can be regarded only as apparent pH values.

Technology. Solutions may be stored in hard glass or polyethylene bottles fitted with a tight
closure or carbon dioxide-absorbing tube (soda lime). Fresh solutions should be prepared at
intervals not to exceed 3 months using carbon dioxide-free water. The table indicates the pH of
the buffer solutions as a function of temperature. The instructions presented here are for the
preparation of solutions having the designated molal (m) concentrations. For convenience, and to
facilitate their preparation, however, instructions are given in terms of dilution to a 1000-mL
volume rather than specifying the use of 1000 g of solvent, which is the basis of the molality
system of solution concentration. The indicated quantities cannot be computed simply without
additional information.
VISCOSITY
Viscosity is a property of liquids that is closely related to the resistance to flow. It is defined in
terms of the force required to move one plane surface continuously past another under specified
steady-state conditions when the space between is filled by the liquid in question. It is defined as
the shear stress divided by the rate of shear strain. The basic unit is the poise; however,
viscosities commonly encountered represent fractions of the poise, so that the centipoise (1 poise
= 100 centipoises) proves to be the more convenient unit. The specifying of temperature is

important because viscosity changes with temperature; in general, viscosity decreases as

temperature is raised. While on the absolute scale viscosity is measured in poises or centipoises,
for convenience the kinematic scale, in which the units are stokes and centistokes (1 stoke = 100
centistokes) commonly is used. To obtain the kinematic viscosity from the absolute viscosity, the
latter is divided by the density of the liquid at the same temperature, i.e., kinematic viscosity =
(absolute viscosity)/(density). The sizes of the units are such that viscosities in the ordinary
ranges are conveniently expressed in centistokes. The approximate viscosity in centistokes at
room temperature of ether is 0.2; of water, 1; of kerosene, 2.5; of mineral oil, 20 to 70; and of
honey, 10,000.
Absolute viscosity can be measured directly if accurate dimensions of the measuring instruments
are known, but it is more common practice to calibrate the instrument with a liquid of known
viscosity and to determine the viscosity of the unknown fluid by comparison with that of the
known.
Many substances, such as the gums employed in pharmacy, have variable viscosity, and most of
them are less resistant to flow at higher flow rates. In such cases, a given set of conditions is
selected for measurement, and the measurement obtained is considered to be an apparent
viscosity. Since a change in the conditions of measurement would yield a different value for the
apparent viscosity of such substances, the instrument dimensions and conditions for
measurement must be closely adhered to by the operator.
Measurement of Viscosity The usual method for measurement of viscosity involves the
determination of the time required for a given volume of liquid to flow through a capillary. Many
capillary-tube viscosimeters have been devised, but Ostwald and Ubbelohdeviscosimeters are
among the most frequently used. Several types are described, with directions for their use, by the
American Society for Testing and Materials (ASTM, D-445). The viscosity of oils is expressed
on arbitrary scales that vary from one country to another, there being several corresponding
instruments. The most widely used are the Redwood No. I and No.II, the Engler, the Saybolt
Universal, and the SayboltFurol. Each of these instruments uses arbitrary units that bear the
name of the instrument. Standard temperatures are adopted as a matter of convenience with these
instruments. For the Saybolt instruments, measurements usually are made at 100F and 210F;
Redwood instruments may be used at several temperatures up to 250F; and values obtained on

theEngler instrument usually are reported at 20 type of instrument is a rotational viscosimeter,

which utilizes a bob or spindle immersed in the test specimen and measures the resistance to
movement of the rotating part. Different spindles are available for given viscosity ranges, and
several rotational speeds generally are available. Other rotational instruments may have a
stationary bob and a rotating cup. The Brookfield, Rotouisco, and Stormerviscosimeters are
examples of rotating-bob instruments, and the MacMichael is an example of the rotating-cup
instrument. Numerous other rotational instruments of advanced design with special devices for
reading or recording, and with wide ranges of rotational speed, have been devised.
Calculations C and 50
C. A particularly convenient and rapid
Where only a particular type of instrument is suitable, the individual monograph so indicates.
For measurement of viscosity or apparent viscosity, the temperature of the substance being
measured must be accurately controlled, since small temperature changes may lead to marked
changes in viscosity. For usual pharmaceutical purposes, the temperature should be held to
within 0.1.
Procedure for Cellulose Derivatives Measurement of the viscosity of solutions of the highviscosity types of methylcellulose is a special case, since they are too viscous for the commonly
available viscosimeters. The Ubbelohdeviscosimeter may be adapted (cf. ASTM, D-1347) to the
measurement of the ranges of viscosity encountered in methylcellulose solutions.
Calibration of Capillary-Type Viscosimeters Determine the viscosimeter constant, k, for each
viscosimeter by the use of an oil of known viscosity. *
Ostwald-Type Viscosimeter Fill the tube with the exact amount of oil (adjusted to 20.0 0.1
specified by the manufacturer. Adjust the meniscus of the column of liquid in the capillary tube
to the level of the top graduation line with the aid of either pressure or suction. Open both the
filling and capillary tubes in order to permit the liquid to flow into the reservoir against
atmospheric pressure. [NOTEFailure to open either of these tubes will yield false values.]
Record the time, in seconds, for liquid to flow from the upper mark to the lower mark in the
capillary tube.
Ubbelohde-Type Viscosimeter Place a quantity of the oil (adjusted to 20.0 0.1 tube, and
transfer to the capillary tube by gentle suction, taking care to prevent bubble formation in the
liquid by keeping the air vent tube closed. Adjust the meniscus of the column of liquid in the

capillary tube to the level of the top graduation line. Open both the vent and capillary tubes in
order to permit the liquid to flow into the reservoir against atmospheric pressure. [NOTE
Failure to open the vent tube before releasing the capillary tube will yield false values.] Record
the time, in seconds, for the liquid to flow from the upper mark to the lower mark in the capillary
tube.
Calculate the viscosimeter constant, k, from the equation:
k=v/dt
in which v is the known viscosity of the liquid in centipoises, d is the specific gravity of the
liquid tested at 20/20, and t is the time in seconds for the liquid to pass from the upper mark to
the lower mark.
UNIFORMITY OF DOSAGE UNITS
The test for Weight Variation is applicable for the following dosage forms:
To ensure the consistency of dosage units, each unit in a batch should have a drug substance
content within a narrow range around the label claim. Dosage units are defined as dosage forms
containing a single dose or a part of a dose of drug substance in each unit.
The term uniformity of dosage unit is defined as the degree of uniformity in the amount of the
drug substance among dosage units. Therefore, the requirements of this chapter apply to each
drug substance being comprised in dosage units containing one or more drug substances, unless
otherwise specified in the individual monograph.
The uniformity of dosage units can be demonstrated by either of two methods, Content
Uniformity or Weight Variation.
solids (including sterile solids) that are packaged in single-unit containers and that contain active
or inactive added substances, except that the test for Weight Variation may be applied in the
special situations stated in (W2) and (W3) below.
(W3)solids (including sterile solids) that are packaged in single-unit containers, with or without
added substances, whether active or inactive, that have been prepared from true solutions and
freeze-dried in the final containers and are labeled to indicate this method of preparation
CONTENT UNIFORMITY

Select not fewer than 30 units, and proceed as follows for the dosage form designated. Where the
amount of drug substance in a single dosage unit differs from that required in the Assay, adjust
the degree of dilution of the solutions and/or the volume of aliquots so that the concentration of
the drug substances in the final solution is of the same order as that obtained in the Assay
procedure; or, in the case of a titrimetric assay, use a titrant of a different concentration, if
necessary, so that an adequate volume of titrant is required (see Titrimetry 541); see also
Procedures under Tests and Assays in the General Notices and Requirements. If any such
modifications are made in the Assay procedure set forth in the individual monograph, make the
appropriate corresponding changes in the calculation formula and titration factor.
1.Prepare a composite specimen of a sufficient number of dosage units to provide the amount of
specimen called for in the Assay in the individual monograph plus the amount required for the
special Procedure for content uniformity in the monograph by finely powdering tablets or mixing
the contents of capsules or oral solutions, suspensions, emulsions, gels, or solids in single-unit
containers to obtain a homogeneous mixture. If a homogeneous mixture cannot be obtained in
this manner, use suitable solvents or other procedures to prepare a solution containing all of the
drug substance, and use appropriate aliquot portions of this solution for the specified procedures.
2.Assay separate, accurately measured portions of the composite specimen of capsules or tablets
or suspensions or inhalations or solids in single-unit containers, both (a) as directed in the Assay,
and (b) using the special Procedure for content uniformity in the monograph.
3.Calculate the weight of drug substance equivalent to 1 average dosage unit, by (a) using the
results obtained by the Assay procedure, and by (b) using the results obtained by the special
procedure.
4.Calculate the correction factor, F, by the formula:
F = W/P in which W is the weight of drug substance equivalent to 1 average dosage unit obtained
by the Assay procedure, and P is the weight of drug substance equivalent to 1 average dosage
unit obtained by the special procedure. If F is greater than 10, the use of a correction factor is not
valid.
5.The correction factor is to be applied only if F is not less than 1.030 nor greater than 1.100, or
not less than 0.900 nor greater than 0.970. If F is between 0.970 and 1.030, no correction is
required.

6.If F lies between 1.030 and 1.100, or between 0.900 and 0.970, calculate the weight of drug
substance in each dosage unit by multiplying each of the weights found using the special
procedure by F.
Uncoated, Coated, or Molded Tablets, Capsules, Oral Solutions in Single-Unit Containers, Oral
Suspensions or Oral Emulsions or Oral Gels in Single-Unit Containers, and Solids (including
Sterile Solids) in Single-Unit Containers Assay 10 units individually as directed in the Assay
in the individual monograph, unless otherwise specified in the Procedure for content uniformity
in the individual monograph. Calculate the acceptance value.
.

WEIGHT VARIATION
no dosage unit result can be less than (1 L2*0.01)M, while on the high side no dosage unit
result can be greater than (1 + L2*0.01)M. (This is based on an L2 value of 25.0.)
otherwise specified in the individual monograph
Suppositories, Transdermal Systems, and Inhalations Packaged in Premetered Dosage Units
[NOTEAcceptance value calculations are not required for these dosage forms.] Assay 10 units
individually as directed in the Assay in the individual monograph, unless otherwise specified in
the Procedure for content uniformity.
Select not fewer than 30 dosage units, and proceed as follows for the dosage form designated.
The result of the Assay, obtained as directed in the individual monograph, is designated as result
A, expressed as % of label claim (see Calculation of Acceptance Value). Assume that the
concentration (weight of drug substance per weight of dosage unit) is uniform. [NOTE
Specimens other than these test units may be drawn from the same batch for assay
determinations.]
Uncoated or Film-Coated Tablets Accurately weigh 10 tablets individually. Calculate the drug
substance content, expressed as % of label claim, of each tablet from the weight of the individual
tablet and the result of the Assay. Calculate the acceptance value.
Hard Capsules Accurately weigh 10 capsules individually, taking care to preserve the identity
of each capsule. Remove the contents of each capsule by a suitable means. Accurately weigh the

emptied shells individually, and calculate for each capsule the net weight of its contents by
subtracting the weight of the shell from the respective gross weight. Calculate the drug substance
content, expressed as % of label claim, of each capsule from the net weight of the individual
capsule content and the result of the Assay. Calculate the acceptance value.