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THE FORMULATION AND EVALUATION OF
UREA CONTAINING PRODUCTS

Cornelia Isabella Claasen

B.Pharm. (PU vir CHO)

Dissertation submitted in partial fulfilment of the requirements for
the degree Magister Scientiae in the Department of Pharmaceutics,
School of Pharmacy, at the Potchefstroomse Universiteit vir
Christelike Hoer Ondenvys

Supervisor: Mrs. E. Swanepoel
Co-supervisor: Prof. A.P. Lotter

POTCHEFSTROOM
2003

To my wonderful parents and fiand Johan.

ACKNOWLEDGEMENTS
I would like to express my sincere appreciation and gratitude to people who have
assisted me in various ways throughout my research.
First and above all, to God Almighty, thank you for giving me all this wonderful
opportunities and people to work with. For the strength and grace you blessed my
way every day of my life. Thank you for the endurance and ability to complete
my study.

8

Mrs. Erna Swanepoel for never turning me away and for helping me
with my study right from the beginning without any delay. For going
out of her way to provide me with answers and make my study go as
smooth as possible.

8

Prof. A.P. Lotter, for his invaluable, genius help throughout this study,
and especially with the formulation of my products.
Dr. J.L. du Preez, for his friendly assistance with the HPLC.
Dr. W. Liebenberg for her interest in my work.

8

Suzan May, for her help with the viscosity tests.
Personnel at the Research Institute for Industrial Pharmacy (HPLCLab), for their help, friendship and interest while working in the
HPLC-laboratory.
My parents, for believing so much in me to give me the opportunity to
study, for encouragement, love, support and a lot of prayers.

8

My friends, Renchk, Sonique, Nicble and all the M-students of the
RIIP in 2003 for their friendship and encouragement.
Nicble Stieger, for the revision of the grammar and style of the
dissertation.
My fianc6, Johan, for his constant love, support and patience. His
encouragement throughout my study gave me inspiration.

TABLE OF CONTENTS
VIII

ABSTRACT
UITTREKSEL
AIM AND OBJECTIVES

X

XI1

CHAPTER 1: PHYSICO- PROPERTIES, FUNCTION AND
USES OF UREA
1.1 Introduction
1.2 The history of urea and moisturisers
1.3 Cosmeceutics and delivery systems
1.3.1 The skin and its permeability
1.3.2 Structural basis for percutaneous absorption pathways
1.3.3 Transcellular vs. intercellular pathways
1.3.4 Skin moisturisers

1.4 Pharmacological action
1.5 Physical and chemical properties
1.6 Stability
1.7 Uses
1.8 Adverse effects
1.9 Precautions and contraindications
1.10 Antimicrobial activity
1.11 Conclusion

CHAPTER 2: FORMULATION OF PRODUCTS
CONTAINING UREA
2.1 Introduction
2.2 Formulation of a hair gel
2.2.1

Purpose and function of a gel
Factors considered to cause hair loss

2.2.1.1

2.2.2 Formulation
2.2.3

Method

2.3 Formulation of a shampoo
2.3.1 Purpose and function of a shampoo
2.3.1.1
2.3.2

Qualities characteristic to shampoos

Formulation

2.3.3 Method

2.4 Formulation of a face toner
2.4.1

Purpose and formulation of a face toner

2.4.2 Formulation
2.4.3 Method

2.5 Formulation of a facial cleanser
2.5.1

Purpose and function of a facial cleanser

2.5.2

Formulation

2.5.3 Method

2.6 Formulation of a cream
2.6.1 Purpose and function of a cream
2.6.2

Day cream

2.6.2.1

Formulation

2.6.2.2

Method

2.6.3

Foot and heel balm

2.6.3.1

Formulation

2.6.3.2

Method

2.6.4 Body cream
2.6.4.1

Formulation

2.6.4.2

Method

2.7 Materials used in the formulations
2.7.1 Active ingredient
2.7.2

Solvents

2.7.3 Preservatives
2.7.4

Others

2.8 Conclusion

CHAPTER 3: STABILITY TESTING
3.1 Introduction
3.2 Stability program
3.2.1 Storage temperatures
3.2.2 Stability tests conducted

3.3 Test methods
3.3.1 HPLC
3.3.1.1

HPLC analysis of urea concentration

3.3.1.2

HPLC analysis of preservative concentration

3.3.1.2.1

Methylparaben and propylparaben

3.3.1.2.2

Phenoxyethanol

3.3.2 Gas chromatography
3.3.3

Urea release with enchancer cell (dissolution testing)

3.3.4

pH

3.3.5 Relative density
3.3.6 Viscosity
3.3.7

Spreadability

3.3.8 Appearance
3.3.9 Penetration
3.3.10 Preservative efficacy

3.4 Conclusion

CHAPTER 4: RESULTS AND DISCUSSION
4.1 Facial toner
4.1.1 pH
4.1.1.1

Discussion

4.1.2 Relative density
4.1.2.1 Discussion
4.1.3 Appearance
4.1.4 Urea assay
4.1.4.1

Discussion

4.1.5 Ethanol assay
4.1.5.1 Discussion
4.1.6

Preservative efficacy

4.1.6.1 Discussion
4.2 Shampoo

4.2.1 pH
4.2.1.1

Discussion

4.2.2 Relative density
4.2.2.1

Discussion

4.2.3 Appearance
4.2.4 Viscosity
4.2.4.1

Discussion

4.2.5 Urea assay

4.2.5.1 Discussion
4.2.6 Preservative efficacy
4.2.6.1 Discussion

4.3 Hair gel
4.3.1 pH
4.3.1.1 Discussion
4.3.2 Relative density
4.3.2.1 Discussion
4.3.3 Appearance
4.3.4 Viscosity
4.3.4.1 Discussion
4.3.5 Urea assay
4.3.5.1 Discussion
4.3.6 Urea release
4.3.6.1 Concentration of urea released from the hair gel
4.3.6.2 Discussion
4.3.7 Preservative efficacy
4.3.7.1 Discussion

4.4 Facial cleanser
4.4.1 pH
4.4.1.1 Discussion
4.4.2 Relative density
4.4.2.1 Discussion
4.4.3 Appearance
4.4.4 Viscosity
4.4.4.1 Discussion
4.4.5 Urea assay
4.4.5.1 Discussion
4.4.6 Methyl- and propylparaben assay
4.4.6.1 Discussion
4.4.7 Preservative efficacy

4.4.7.1 Discussion

4.5 Day cream
4.5.1 pH
4.5.1.1 Discussion
4.5.2 Relative density
4.5.2.1 Discussion
4.5.3 Appearance
4.5.4 Viscosity
4.5.4.1 Discussion
4.5.5 Urea assay
4.5.5.1

Discussion

4.5.6 Methyl- and propylparaben assay
4.5.6.1 Discussion
4.5.7 Preservative efficacy
4.5.7.1 Discussion
4.6 Foot and heel balm
4.6.1 pH
4.6.1.1

Discussion

4.6.2 Appearance
4.6.3

Spreadability

4.6.3.1

Discussion

4.6.4 Penetration
4.6.4.1

Discussion

4.6.5 Urea assay
4.6.5.1 Discussion
4.6.6

Methyl- and propylparaben assay

4.6.6.1

Discussion

4.6.7

Urea release
4.6.7.1 Concentration of urea released from foot and heel balm
4.6.7.1.1

4.6.8

Discussion

Preservative efficacy

4.6.8.1

96

Discussion

4.7 Urea body cream

97

4.7.1 pH
4.7.1.1

97
97

Discussion

4.7.2

Appearance

98

4.7.3

Spreadability

98

4.7.3.1
4.7.4

101
102

Discussion

102

Concentration of urea released from the urea body cream

4.7.7.1.1

103
106

Discussion

107

Preservative efficacy

4.7.8.1

4.8

100

Discussion

Urea release

4.7.7.1

4.7.8

99

Phenoxyethanol assay

4.7.6.1
4.7.7

99

Discussion

Urea assay

4.7.5.1
4.7.6

99

Penetration

4.7.4.1
4.7.5

98

Discussion

108

Discussion

Conclusion

108

BIBLIOGRAPHY

110

PUBLICATION OF CONFERENCE CONTRIBUTIONS
APPENDIX A

VII

ABSTRACT
Almost every person will experience dry skin during his or her lifetime. Many
people experience occasional episodes, but some have a chronic problem with
xerosis that is irritating and troublesome. Moisturisers are the mainstay of
treatment for dry skin, daily maintenance of normal skin, and adjunctive therapy
for many skin diseases (Flynn er al., 2001:387).
The objectives of this study were the formulation and evaluation of urea
containing products. Seven different cosmetic products were formulated: hair
gel, shampoo, facial toner, facial cleanser, day cream, foot and heel balm and a
body cream. The product development program started with a preformulation
study, followed by formulation of the seven skin care products, which were
followed by stability testing, based on the requirements of the South African
Medicines Control Council (2003:21, 22, 23) for new products. The stability of
all skin care products must he matched to the expected period of usage by the
consumer, as well as to the user's requirements. The formulations were tested
under ICH conditions (accelerated stability studies) over a period of three
months at three different storage temperatures, i.e. 5"C, 25"C160%RH,
40°C/75%RH. Stability indicating tests that applied to these formulations, were
conducted: pH, relative density, viscosity, appearance, penetration, spreadability,
assay of urea, the assays of the preservatives and the release study of urea by
means of membrane release.
Chapter 1 gives a literature overview of the skin and the properties and uses of
urea. Chapter 2 deals with the formulation of the urea products and the chemicals
that have been used. Chapter 3 describes the methods used for accelerated
stability testing. Chapter 4 finally deals with the results obtained and the
conclusions that were made.

The test results showed the following: There was a prominent change in the pH
of all the formulated products, this can be due to the decomposition of urea into
carbon dioxide and ammonia (Beiersdorf, 2003). Higher temperature and
moisture increase this decomposition and cause the pH to increase to values as
high as 9 (Anon, 2003:20). However, urea compositions can be stabilised when
they contain methylsulfonylmethane (MSM) (Herschler, 1981:l).
The viscosity, spreadability, penetration, relative density and appearance of the
products remained more or less the same over three months, except for the day
cream and the facial cleanser where phase separation occured after 1 month. The
urea content decreased with time, but only dropped to below 90% in the day
cream after 3 months at 4O0C/75% RH. HPLC analysis of the preservatives
confirmed their stability in the formulated products. The preservative efficacy
results proved that the products were sufficiently protected from microbial
contamination.
The release study indicated that urea is released at a steady rate from the
preparations tested. The release of urea from the hair gel is about four times
faster than that from the body cream and the foot and heel balm. In general, the
release is influenced by the viscosity of the medium and should be faster from
the gel than from the creams (Shah er al., 1991:55).
In conclusion it can be said that urea was successfully formulated into the seven
cosmetic products except for the facial cleanser and day cream which must be
stabilised.

UITTREKSEL
Bykans elke mens sal gedurende sy of haar lewe droe vel ervaar. Baie mense
ervaar periodieke episodes, maar ander het 'n chroniese probleem met xerose wat
baie irriterend is. Bevogtigers is die hoofbehandeling vir droe vel, daaglikse
instandhouding van 'n normale vel en bykomende terapie vir baie velsiektes
(Flynn et al., 2001:387).
Die doelstellings van hierdie studie was die formulering en evaluering van ureum
bevattende produkte.

Sewe produkte was geformuleer: haarjel, sjampoe,

gesigsreiniger, verfrisser, dagroom, voet- en hakhalsem en 'n lyfroom. Die
produkontwikkelingprogram het begin met 'n preformuleringstudie, gevolg deur
die formulering van die sewe produkte. Daarna het stabiliteitstoetse gevolg soos
vereis deur die Medisynebeheerraad van Suid-Afrika vir nuwe produkte. Die
tydperk van gebruik van die velprodukte, asook die vereistes van die gebruiker,
moet in ag geneem word tydens die stabiliteitstoetse. Die formulerings was onder
ICH kondisies (versnelde stabiliteitstoetse) getoets oor 'n periode van drie
maande by drie verskillende temperature, nl. 5"C, 25"C/60%RH, 4OoC/75%RH.
Stabiliteitstoetse wat op hierdie formulerings van toepassing was sluit in: pH,
relatiewe digtheid, viskositeit, voorkoms, penetrasie, spreibaarheid, die analise
van ureum en preserveermiddels en die vrystellingstudie van ureum d.m.v.
memhraanvrystelling.
Hoofstuk 1 gee 'n literatuuroorsig van die vel en die eienskappe en gebruike van
urea. Hoofstuk 2 handel oor die formulering van die urea bevattende produkte en
die chemikaliee wat gehruik was. Hoofstuk 3 verduidelik die metodes wat
gebruik was vir die versnelde stabiliteitstoetse. Hoofstuk 4 handel oor die
resultate wat verkry is en die gevolgtrekkings wat gemaak is.

Die resultate van die toetse was soos volg: Daar was 'n prominente verandering
in die pH van a1 die produkte wat geformuleer was, dit is as gevolg van die
afbraak van urea na koolstofdioksied en ammoniak (Beiersdorf, 2003). Hoer
temperature en hoer vogtigheidskondisies verhoog hierdie afbraak en veroorsaak
dat die pH na waardes so hoog as 9 kan toeneem (Anon, 2003:20). Ureum
bevattende produkte kan gestabiliseer word wanneer metielsulfonielmetaan
(MSM) bygevoeg word (Hershler, 1981:l).
Die viskositeit, spreibaarheid, penetrasie, relatiewe digtheid en voorkoms van die
produkte het min of meer dieselfde gebly oor die drie maande hehalwe in die
geval van die gesigsreiniger en dagroom waar fase-skeiding na 1 maand
plaasgevind het. Die ureum inhoud het met tyd afgeneem, maar slegs in die gaval
van die dagroom tot laer as 90% gedaal. HPLC analise van die preserveermiddels
het hul stabiliteit in die geformuleerde produkte bevestig. Die preserveermiddel
effektiwiteits resultate het bewys dat die produkte genoegsaam heskerm was teen
mikrohiologiese kontaminasie.
Die vrystellingstudie het getoon dat ureum teen 'n konstante tempo uit die
produkte wat getoets was vrygestel is. Die vrystelling van ureum uit die haarjel
is bykans vier keer vinniger as di6 van die voet- en hakbalsem en lyfroom. In die
algemeen, word die vrystelling geaffekteer deur die viskositeit van die medium
en dit hehoort vinniger vanuit die jel as vanuit die rome te wees (Shah et al.,
1991:55).
In gevolgtrekking kan ges& word dat ureum suksesvol in die sewe kosmetiese
produkte geformuleer was en stabiel by hoer temperature bly, behalwe die
gesigsreiniger en die dagroom wat verder gestabiliseer moet word.

AIM AND OBJECTIVES
Urea is one of the most important soluble substances of the stratum corneum. In
recent years this substance has become more and more important in
dermatological therapy and cosmetics. Many diseases have been described that
are characterised by a deficiency of urea, such as atopic dermatitis or clinical dry
skin (Hantscei et a1.,1998:155).
The aim of this study was to develop different stable urea containing topical
formulations for use as cosmetic products. The stability of urea is somewhat of a
problem in water-containing formulas that are stored for a long time because
urea can decompose into carbon dioxide and ammonia (Beiersdorf, 2003).
The main objectives of this study included:

To formulate a facial toner, shampoo, hair gel, facial cream, day cream,
foot and heel balm and a body cream, containing urea.
To subject the urea containing formulations to stability indicating studies
for three months under ICH conditions.
To analyse urea by means of a stability indicating HPLC method.

The physical and chemical evaluation of these products as required by the
South African Medicines Control Council (2003:21,22,23).

To determine the release of urea by means of membrane release studies.
The preservative efficacy testing of these products.

CHAPTER 1

PHYSICO-CHEMICAL PROPERTIES,
FUNCTION AND USES OF UREA

1.1 INTRODUCTION
Almost every person will experience dry skin during his or her lifetime. Many
people experience occasional episodes, but some have a chronic problem with
xerosis that is irritating and troublesome. Moisturisers are the mainstay of
treatment for dry skin, daily maintenance of normal skin, and adjunctive therapy
for many skin diseases (Flynn et al., 2001:387).
Treatment of dry skin is aimed at restoration of the epidermal water barrier. This
is accomplished with moisturising agents that are topically applied to the skin.
Humectants are compounds that attract water from the dermis into the stratum
corneum. Examples of humectants include urea, glycerine, propylene glycol,
sodium lactate, sorbitol, honey, and pyrrolidone carboxylic acid (PCA) (Flynn et
al., 2001:389).

Urea is one of the most important soluble substances of the stratum corneum. In
recent years this substance has become more and more important in
dermatological therapy and cosmetics. Many diseases have been described that
are characterised by deficiency of urea, such as atopic dermatitis or clinical dry
skin. The urea content of normal skin is nearly 1%. It contributes in a significant
manner to the hydration of the stratum corneum. Urea contributes approximately
3-7% to the natural moisturising factor (NMF). The NMF appears to be

responsible for the hydration status of the stratum corneum. Otherwise urea is
known for its keratolytic and pruritus-easing properties, and it is a very potent
humectant in moisturising creams. Its sources in the epidermis are sweat and the
decomposition of arginine by arginase during the process of keratinisation
(Hantschel et al., 1998:155).

1.2 mE HISTORY OF UREA AND MOISTURISERS
Urea was first discovered in human urine by H.M. Rouelle in 1773. It was
synthesised in 1828 by Friedrich Wohler (see Figure 1.1) and was the first
organic compound to be synthesised from inorganic starting materials. It was
found when Wohler attempted to synthesise ammonium cyanate, to continue a
study of cyanates which he had been carrying out for several years. On treating
silver cyanate with ammonium chloride solution he obtained a white crystalline
material which proved identical to urea obtained from urine.

Figure 1.1

Friedrich Wohler

2

This discovery prompted Wohler to write triumphantly to Berzelius:"I must tell you that I can make urea without the use of kIdneys, either man or
dog. Ammonium cyanate is urea" (Fairall, 1996).
The use of moisturisers by mankind has historic roots. Ancient Egyptians
frequently anointed their bodies with oils. The Bible describes applications of
oils to the skin, and Ancient Greek and Roman cultures regularly applied oilcontaining products. Humans have recognised the value of externally applied
lipids for thousands of years, and continue to value them (Flynn et al.,
2001 :387).

1.3 COSMECEUTICS AND DELIVERY SYSTEMS
In the formulation of cosmetic products, active ingredients are combined with a
variety of other compounds that give the product its physical form and may
control the delivery of the active ingredient. By far the most conventional and
widely used cosmetic delivery system is the oil-water emulsion. Most cosmetic
creams and lotions on the market today are emulsions.
The carrier of the system can affect the delivery of active components by a
number of different means, such as interacting with the active agent, controlling
the rate of release from the vehicle, altering stratum corneum resistance, or
enhancing

stratum

corneum

hydration.

Permeation

enhancers

may

be

incorporated in the system to increase the skin delivery of the active agent
(Magdassi & Touitou, 1999:1).

3

1.3.1 The skin and its permeabDity
The skin is not a uniform surface. A mature human weighing 65 kg will have
approximately 18000 cm2 of skin surface area. Figure 1.2 is a diagrammatic
representation of the structure of the human skin (Schaefer et al., 1999:9).

Arrector pili
muscle
Hair bulb
~APocrlne
'~

~
.'V:'~i!

J.. . '.

Figure 1.2

sweat
gland

~AdlPose
tissue
Arteriole
Venule

Diagrammatic representation of four compartments of the skin:

stratum corneum, viable epidermis, dermis, and hipodermis
The superficial region, termed the stratum corneum, is between 10 and 20 ~m
thick. Underlying this region is the viable epidermis (50-100 ~m), dermis (1-2
mm) and hypodermis (1-2 mm). Because of the large surface area as well as the
volume of the compartments, the skin is the body's largest organ, weighing
approximately 7 kg and representing more than ]0% of the total body mass.
Though the skin comprises a very large volume, the barrier to percutaneous
absorption

lies within

compartment (Schaefer

the stratum

corneum,

et al., 1999:9).

4

----

the thinnest

and smallest

The stratum corneum consists of horny cells or corneocytes, which are flat,
polyhedral, non nucleated cells approximately 40 flm long and 0,5 flm in
diameter. The corneocytes are cell remnants of the terminally differentiated
keratinocytes

found in the viable epidermis. Their cellular organelles and

cytoplasm have disappeared during the process of cornification. In turn, this is
accompanied by a remodeling of the remaining protein constituents to form the
corneocytes.

They are composed primarily

of insoluble

bundled keratins

surrounded by a cell envelope stabilized by cross-linked proteins and covalently
bound lipid. Interconnecting the corneocytes of the stratum corneum are polar
structures such as corneodesmosomes, which ascertain the cohesion of the
stratum corneum (Schaefer et al., 1999:10).
Intercellular lipid is generated primarily from the exocytosis of lamellar bodies
during the terminal differentiation of the keratinocytes and, less importantly,
from sebaceous secretion, which is predominantly deposited in the upper layers
of the stratum disjunctum. The intercellular lipid is pivotal for a competent skin
barrier and forms the only continuous domain in the stratum corneum. It follows
a tortuous path within the stratum corneum, a structural feature that may account
in part for the barrier properties of the skin (Schaefer et al., 1999: 10).
The stratum corneum comprises approximately 15 layers, though at sites of
increased pressure (such as the soles at the feet) this number is significantly (5

-

to 10-fold) increased. The upper layer, termed the stratum disjunctum, contains
approximately

3-5 layers and is constantly undergoing

desquamation. The

stratum compactum (lower three layers) is thicker, more densely packed, more
regular,

and contains

structures that more closely reflect the underlying

epidermis. The lower stratum compactum has more water associated with it (30%
by weight) as compared with the stratum disjunctum (15% by weight), though
both are considerably less hydrated than the viable dermis (70% by weight).
These differences correlate with the amino acid and lipid content of the layers.
Further differences are observed for the rigidity of the cellular membranes,

5

perhaps reflecting the maturation process of the corneocyte cell envelope during
the passage from the epidermis to the surface of the skin and the final shedding.
Finally, the stratum compactum has a higher density of corneodesmosomes,
suggesting that their proteolysis

is required for the separation of mature

corneocytes. Taken together, this indicates that the stratum corneum is not
uniform, that it continuously evolves from below to the surface, and that the
layers represent various stages of corneocyte and intercellular lipid maturation
(Schaefer et al., 1999:11).
Adsorption indicates the reversible, noncovalent interaction of compounds with
structures such as the binding of drugs to keratin filaments. It is used to describe
a state and not the process;

it should be differentiated

from the term

substantivity, which refers to reversible binding. The term absorption is used to
describe the process of intake of substances, as by an organism. Percutaneous
absorption is thus a global term describing the passage of compounds across the
skin, though it does not necessarily indicate their eventual fate. The process can
be subdivided into three steps. Penetration is the entry of a substance into a
particular layer or structure, such as the entrance of a compound into the stratum
corneum. It is to be differentiated from the term permeation, which indicates that
the compound has diffused from one layer to another distinct layer. Finally,
resorption is defined as the uptake of substances through the vascular system into
the central or inner compartment. Thus, we do not consider that compounds
which have penetrated into the stratum corneum should be considered to be
absorbed into the body (Schaefer et al., 1999:22).

1.3.2 Structural basis for percutaneous absorption pathways

These routes are referred to as (1) appendiceal, (2) transcellular,

and (3)

intercellular

corneum

(Figure

1.3).

Permeability

through

the

stratum

(transcorneal permeation) may be considered to occur through the intercellular
6

-

lipid domain or through the corneocytes (transcellular route). The relevance of
these routes to percutaneous absorption of a compound depends upon their
number per surface area and path length as well as the diffusivity and solubility
of the compound in each domain. These pathways should not be treated as
mutually exclusive. Hair follicles are the most important appendages in terms of
surface area (Schaefer et 01., 1999: 16).

.

Tran8CeUulal" rout.

Int.ro.IIUI route
:~-~:

;.~

.-

_

-J:

-. -..

L':~'>:~

Pl88m8
membrane

Upfd??

(b)

Figure 1.3

K.r8tln

Model of penetration pathways (Schaefer et 01., 1999: 17)

1.3.3 Transcellular vs. intercellular pathways

The rate-limiting step for permeation includes a hydrophobic barrier -Le., the
intercellular lipid. Available evidence suggests that the only continuous domain
within the stratum corneum is formed by the intercellular lipid space. This
suggests that the majority of compounds penetrating the stratum corneum must
pass through intercellular lipid, though it does not exclude the possibility that
compounds can also enter into the inner lumens of corneocytes.
Low molecular weight moisturisers like glycerol and urea are likely to undergo
partition into the corneocytes and alter their water binding capacity. Thus, the

7

- -- ---

penetration

of compounds into corneocytes

cannot be excluded from the

consideration of percutaneous absorption pathways (Schaefer et al., 1999:16).

1.3.4 Skin moisturisers

In order to retain and bind water at the skin surface, hygroscopic substances are
used. Examples are the active principles of NMF and particularly the sodium salt
of 2-pyrrolidone-5-carboxylic

acid (sodium PCA), a physiological moisturiser

found in various organs, organic fluids and particularly the epidermis, including
the stratum corneum.
Mixtures of sodium PCA, amino acids, urea, lactic acid, sodium lactate, and
trace elements, known as "reconstituted NMFs," are also frequently used. Urea
(around 2-5%) is also capable of increasing hydration of the corneum by 100%,
both by an osmotic effect due to its low molecular weight and for its ability to
solubilise insoluble proteins (Morganti, 1999:80).

1.4 PHARMACOLOGICAL

ACTION

Humectants are compounds that attract water from the dermis into the stratum
corneum. These agents are designed to attract water up into the outer layers of
the epidermis, as opposed to trapping water found in the environment (unless the
relative ambient humidity exceeds 70 to 80%). Moisturisation of the stratum
corneum occurs from below, with the dermis contributing moisturisation to the
skin. Examples of humectants include glycerine, propylene glycol, urea, sodium
lactate, sorbitol, honey, and pyrrolidone carboxylic acid (PCA), (Flynn et ai.,
2001 :389).

8

- - - - --

Moisturisers that contain only humectant elements will draw water into the
stratum corneum but not prevent the hydrated stratum corneum from losing its
increased water content. As such, they can actually increase transepidermal water
loss (TEWL). The use of only humectants in skin with a defective barrier could
actually contribute to a drying function of the outer layer of the skin. Thus,
humectants are usually combined with occlusants (Flynn et al., 2001:389). The
water content of the stratum corueum should be greater than 10% for the skin to
have a normal appearance and not feel rough, scaly, or dry. Ideally, the stratum
corneum should have a 20 to 35% water content. Moisturisers serve to return
water content to the skin with the humectants attracting water from the lower
layers of the epidermis into the stratum corneum, and occlusive ingredients
preventing transepidermal water loss (Flynn et al., 2001:390).
Moisturisers restore epidermal lipids, which play a key role in maintaining the
permeability barrier of the skin as well as increasing its plasticity, it make the
skin feel smoother, a property known as emolliation. Cracks and gaps between
the desquamating corneocytes are filled by moisturiser, decreasing the rough
quality of the skin. Moisturisers also decrease friction on the skin, improving the
lubricity (Flynn er al., 2001:390).
Urea can be added to moisturisers and enhances the water-binding capacity of the
stratum corneum by disrupting bonding. Urea exposes water-binding sites on
corneocytes and promotes desquamation by decreasing the intercellular
cementing substance between the corneocytes. Also, long-term treatment with
urea has been demonstrated to decrease TEWL. A possible explanation may
involve urea-induced reduction in epidermal cell proliferation which, in turn,
increases the size of corneocytes. Larger corneocytes lower skin permeability,
thereby lowering TEWL. It has also been shown that long-term urea application
reduces the susceptibility of the skin to sodium lauryl sulfate irritation. A
possible mechanism may be urea-induced alteration of the binding capacity of
the stratum corneum. This protective effect (after prolonged application) has

promising clinical ramifications for the use of urea-containing moisturisers to
reduce contact dermatitis from irritant stimuli (Flynn et al., 2001 :391).

According to Parima (2003) urea gently dissolves the intercellular matrix which
results in loosening the horny layer of skin and shedding scaly skin at regular
intervals, thereby softening hyperkeratotic areas. Urea also hydrates and gently
dissolves the intercellular matrix of the nail plate, which can result in the
softening and eventual debridement of the nail plate.

1.5 PHYSICAL AND CHEMICAL PROPERTIES
In Figure 1.4 is a model of the structure of the urea molecule. Table 1.1 summarises the
physical and chemical properties of urea.

Figure 1.4 Model of the urea molecule

10

Table 1.1 Physical and chemical properties of urea (Chimco ad., 1997).
Chemical name

Carbamide

Commonly used synonyms

Urea

Molecular formula

CO(NH2)z

Appearance

Colourless to white, prismatic c~ystalsor as a white,
crystalline powder.
Odourless but may gradually develop a slight ammoniacal
odour on long standing (AHFS Drug Information@,
2002:3457).

pH water solution

9-10

(conc.lO%)
Melting point

133°C (decomposes)

Flammability (solids)

Not flammable

Explosive properties

Uncontaminated urea is not an explosion hazard. However, it
may form explosive mixture subject to spontaneous
detonation when contaminated with strong acid (nitric or
perchloric) or nitrates.

Oxidising properties

None

Bulk density
Solubility in water

1.6 STABILITY
Upon standing, heating, or exposure to acids or alkalies, urea is hydrolysed to ammonia
and carbon dioxide. Solutions of urea are unstable and cannot be sterilised by heat. Urea
should be stored in wellclosed containers (AHFS Drug Information@,2002: 3457).

1.7 USES
Urea is used topically in the treatment of dry skin. At concentrations of 5-30%, urea
promotes hydration of keratin and mild keratolysis in dry and hyperkeratotic skin. Urea
increases the uptake of water by the stratum corneum, giving it a high water-binding
capacity. Topically applied urea may also have an antipruritic effect. At high
concentrations (e.g., 40%), urea is a protein denaturant (AHFS Drug Information@,2002:
3457).

Parima Inc. (2003) reported use of urea as treatment for:
0

Direct diuretic
Wounds
Athlete's foot
Perfusions used in neurosurgery
Urea infusions
Water retention
Urinary infection without renal lesions
Cancer
Hyperkeratotic conditions such as:
9 Dry skin

D Rough skin
9 Dermatitis
9 Psoriasis

D Xerosis
D Ichthyosis
D Eczema
9 Keratosis

D Keratoderma
9 Corns
9 Calluses

D Damaged, ingrown and devitalized nails
According to Parima (2003) urea is effective for debridement and promotion of
normal healing of hyperkeratolic surface lesions, particularly where healing is
retarded by local infection, necrotic tissue, fibrinous or prurient debris or eschar.
Urea is a direct diuretic, meaning it can increase diuresis by boosting the
function of the renal epithelia (Robert & Fils, 2000).
Wounds can be treated by spraying urea or a 2% solution of same. In Russia
more concentrated solutions of urea are used to treat athlete's foot and certain
related pathologies. In France urea is used in perfusions, with 500 ml flasks
containing 90 g of pure urea. These perfusions are used in neurosurgery (before,
during, or after) to treat brain swelling and during eye surgery (Robert & Fils,
2000).
Urea can also be taken internally: one or two grams per day are used as a
treatment for water retention and related problems (such as swollen face,
headaches, premenstrual water retention, enuresis). Urea can also be used to treat
urinary infection in the absence of lesions. Urea possesses interesting
bacteriostatic and antibacterial activities (Robert & Fils, 2000).
As far as its effect on cancerous cells, urea seems to have an antiangiogenic
activity, as well as destabilising the fibrin that forms the stroma that "blankets"
the tumour, and can make up 50% of the tumor mass. It seems that urea modifies
the tumor's support and exposes its peripheral characteristics to the immune
system (Robert & Fils, 2000).

1.8 ADVERSE EFFECTS
When used in appropriate dosage, topically applied urea preparations have a low
order of toxicity. Transient stinging may occur, especially when urea
preparations are applied to the face or broken or inflamed skin. Local irritation
may also occur following topical application of urea (AHFS Drug Information@,

2002:3457).

1.9 PRECAUTIONS AND CONTRAINDICATIONS
Topical preparations containing urea are intended for external use only. Topical
preparations should be applied with caution to the face or broken or inflamed
skin. Urea should not be used near the eyes.
Some commercially available topical formulations of urea that contain sulfites
may cause allergic-type reactions, including anaphylaxis and life-threatening or
less severe asthmatic episodes, in certain susceptible individuals. The overall
prevalence of sulfite sensitivity in the general population is unknown but
probably low, such sensitivity appears to occur more frequently in asthmatic than
in nonasthmatic individuals. Topical urea preparations should be discontinued if
irritation or rash occurs during use (AHFS Drug Information@, 2002:3457).

1.10 ANTIMICROBIAL ACTIVITY
Although it is not yet entirely clear why urine has a germicidal and antiseptic
effect, it is known that urea plays an important role here. Ammonia and salt
also have a similar purifying effect. Besides killing bacteria, urine also inhibits

or destroys various viruses and fungi. Scientific research has demonstrated that
both urea and ammonia have a powerful anti-viral effect. Applying urine to a
fresh cut or scrape prevents infection and keeps flies away. Compresses from
fresh or old urine help to combat infections and often cause them to disappear.
Although urine does not entirely prevent the growth of bacteria in the urethra, it
clearly has a powerful antiseptic effect when externally applied (Anon, 1999:7).
Urea is an oxidising substance which ensures that the disintegrating proteins
(proteins in the area of a wound or inflammation) dissolve. If urea is present,
disintegrating tissue cannot feed itself with other rotting material. It dissolves
fats and other natural body secretions. Urea is even more effective when heated.
Due to its strong anti-bacterial nature, urine has an inhibitive effect on the
growth of tuberculosis bacille. Bacteria-inhibiting or bacteria-killing effects of
urine increase with decreasing pH. Urea and ammonia, closely related, play an
important role here. When brought in contact with urea, complex polymers are
transformed or decomposed into monomers, which can then be endured by the
body (Anon, 1999:7).

1.11 CONCLUSION
In conclusion it can be said that urea possesses all the properties that is
necessary to treat hyperkeratosis, dryness, ichthyosis and as therapy in allergic
(atopic) eczema. Therefore, if it is incorporated into dermatological vehicles and
properly analysed and evaluated, there is a possibility that these products could
be effective in the treatment of these skin problems.

CHAPTER 2
FORMULATION OF PRODUCTS
CONTAINING UREA

2.1 INTRODUCTION
Urea is one of the most important end products of human protein metabolism. It
has been used for many years in the treatment of chronic dry skin conditions as it
is a moisturising factor (Hantschel et al., 1998:155).
However, the stability of urea is somewhat of a problem in water-containing
formulas that are stored for a long time. Urea can decompose into carbon dioxide
and ammonia. These problems have been solved in pharmaceutical preparations
by the inclusion of suitable stabilisers such as sodium lactate whereby the
decomposition of urea into ammonia is minimised (Beiersdorf, 2003). The most
appropriate solvents for urea are water and a waterlpropylene glycol (1:l in
volume) mixture (Gallardo et al., 1990:845).
According to Dermadoctor.com. (2002) a concentration of 5-10% urea helps deep
clean dry itchy scalp. Antibacterial agents help kill yeast and bacteria that
contribute to scaly dry skin and dandruff flares.
The formulations that were developed included a hair gel, shampoo, facial toner,
facial cleanser, day cream, foot and heel balm and a body cream.

2.2 FORMULATION OF A HAIR GEL

2.2.1 Purpose and function of a gel
Gels are a type of base which produce a uniform external appearance, range from
transparent to semitransparent and give a moist feeling. Aqueous gels have been
used in cosmetics because of their special feature of light feeling.
Aqueous gels contain a lot of moisture, they are used as a base material with
water supplying, moisturising and cooling effects or as the base in cleansers for
removing light makeup (Mitsui, 1997:351).
Hair growth promoters are preparations made by adding various pharmaceutical
agents which are applied to the scalp to normalise its functions. By increasing
the circulation in the scalp, they improve hair follicle function which in turn
promotes hair growth and prevents hair loss. They also help prevent dandruff and
itchiness (Mitsui, 1997:413).

2.2.1.1

Factors considered to cause hair loss
Reduced hair follicle function due to male hormones.
Reduction in metabolic functions of hair follicles and hair bulbs. It is the
division, proliferation and differentiation of the hair matrix at the hair
roots which form hair and make it grow up to the epidermis. The hair
matrix receives the supply of nutrients that it requires for cell division
from the capillaries in the dermal papilla. Therefore, if the flow of blood
in the capillaries surrounding the hair follicles and dermal papilla is
reduced, the supply of nutrients to the dermal papilla and matrix will not

be sufficient, hence impairing cell metabolism and having an adverse
effect on hair growth (Mitsui, 1997:414).
0

Reduction in scalp physiological functions. Excessive build-up of
dandruff flakes will block the pores of the scalp through which hairs exit
the epidermis. This will have an adverse effect on the hair production at
the hair root and the substances formed when the dandruff is decomposed
by bacteria will irritate the scalp giving rise to such conditions as
pityriasis accompanied by itching and inflammation. Leaving this
untreated will cause the hair loss to spread giving rise to the condition
known as pityriasis type hair loss. If the sebaceous glands in the upper
part of the follicles secrete too much sebum, this will produce irritation to
the scalp when decomposed by the bacteria on it and may give rise to
sehorrhoea alopecia (Mitsui, 1997:415).
Local impairment of circulation due to tension in the scalp. A loss in
flexibility in the scalp will cause a reduction in the flow of blood in the
peripheral blood vessels in the subcutaneous tissue of the scalp adversely
affecting hair growth (Mitsui, 1997:415).

2.2.2 Formulation
A very simple glycerine-containing treatment consists of 5-10 parts urea, 3-5
parts glycerine, and 100 parts water. This recipe is claimed to increase the
volume of the hair, as well as act as a treatment for seborrhea and other scalp
diseases. Effective or not for seborrhea, it should certainly provide a strong
moisturising treatment. Glycerine has been claimed as an essential ingredient in
a hair growth stimulant (Jnngermann, 1991:374). The final formula for the hair
gel is given in Table 2.1.

Fable 2.1 Hair gel formula

Activity

INGREDIENTS

A. Carhop01 Ultrez

Gel forming agent

B. Tris (hydroxymethyl)

pH-adjustment for
gelling

aminomethane
Disodium EDTA

Completing agent

Water

C. Urea

Solvent
Active (moisturiser)

Propylene glycol

Moisturiser

Glycerine

Moisturiser

Distilled Water

Solvent

2.2.3 Method
Dissolve urea and 50 ml of water from C in a glass beaker and add the propylene
glycol and glycerine. No heating is required because of the high solubility of
urea in water. Add A to C and homogenise thoroughly. Remove the foam
manually. Mix B and dissolve in 3.0 ml of water and add B to C.

2.3 FORMULATION OF A SHAMPOO

2.3.1 Purpose and function of a shampoo
A shampoo is a hair-wash cosmetic used to remove dirt from the scalp and the
hair, treat dandruff and itchiness and maintain the hair in a clean and beautiful
condition. In order to do this, it must have an appropriate level of cleansing
power which is sufficient to remove all the dirt but will not remove too much

sebum, which is very necessary for the scalp and hair. The final formula for the
shampoo is given in Table 2.2.
There is a great variety of shampoos which, in addition to their main function of
cleansing, have added value in the form of conditioning, luster enhancing and
styling capabilities (Mitsui, 1997:407).

2.3.1.1 Qualities characteristic to a shampoo
Shampoo must have the following qualities:
An appropriate cleansing ability.
Produce a lasting, rich, creamy lather.
Protect the hair from friction damage during washing.
The hair must have a natural luster and an appropriate softness after it has
been washed, and
They must be very safe with respect to the scalp, hair and eyes (Mitsui,
1997:407).

2.3.2 Formulation
Table 2.2 Shampoo formula

INGREDIENTS
A. Urea

% mlm
5%

Activity

I Active (moisturiser)

Sodium lactate (88%)

5%

Stabiliser

Distilled water

1%

Solvent

B. Texapon N 70

14%

Surface active agent

C. Distilled water

70,5%

Solvent

4,5%

Thickening agent

Sodium chloride

2.3.3 Method
Dissolve the sodium chloride in C in a small amount of water, add insoluble B.
Add the rest of the water. Then add and mix A to the BC mixture.

2.4 FORMULATION OF A FACIAL TONER
2.4.1 Purpose and function of a facial toner
A toner is the most important part of skin care. If you do not tone your skin
before applying your moisturisers or treatment serums, then you are simply
fooling yourself into believing that you are taking care of your skin. Applying
anything on your face without toning first is useless (Westervelt, 1997:l). It
refreshes, tones and moisturises the skin and prepares the skin for application of
skin care (Anon, 2003:Z). The final formula for the facial toner is given in Table

2.3.
Contrary to common belief, a toner is not just a skin conditioner. It is much more
than that. A toner performs 4 very essential acts that no other skin care product
on the market can do:
It DEEP CLEANSES and purifies your pores, making sure that all pores
are totally clear of leftover make-up, dirt, dead skin cells, toxins and other
hazardous elements. It's especially important for clearing the skin of
impurities found in tap water. Analyze tap water and you'll discover
fluoride, chlorine and sodium which clog the pores and are very
dehydrating. If this debris is not removed, you are only forcing it deeper
into your pores as you apply moisturiser on top, trapping the debris that
can cause bumps, blackheads, enlarged pores, improper absorption of the
moisturiser, rough texture and even acne (Westervelt, 1997:l).

It BALANCES the pH level or the natural acid mantle that protects your
skin from the environment. Not too acid, not too alkaline. It can take your
skin up to 30 minutes to rebalance itself after cleansing without using a
toner because the sebaceous or oil glands are confused.
HYDRATION is cmcial for proper cell function. Skin can be oil dry
andlor moisture dry and the moisture content is more crucial to skin
health. A toner is a very nourishing form of moisture that even a
moisturiser cannot provide. Also, the environment is constantly robbing
your skin of hydration, especially during heat season and while travelling.
PENETRATION of treatment and moisturisers means complete absorption
of the potent nutrients, those nutrients absorbing deeper, more effectively
and evenly into your skin (Westervelt, 1997:2).

2.4.2 Formulation
Table 2.3 Facial toner formula
% mlm

INGREDIENTS

A. CremophorB RH 40
B. Propylene glycol USP

1

1,5%
3%

Activity
Solubiliser
Moisturiser

Ethanol 96%

Preservative

Witch Hazel

Astringent

Urea
Sodium lactate (60%)
Distilled water

I

Active (moisturiser)
Stabiliser
Solvent

2.4.3 Method
Solubilise phase A. Mix the components of phase B to a solution and stir into
phase A. Adjust the pH to 5-6

2.5 FORMULATION OF A FACIAL CLEANSER

2.5.1 Purpose and function of a facial cleanser
The most important considerations to be made regarding face cleansing
cosmetics, the first step in any cosmetic routine, are:
the object to be cleansed (skin ),
the type of dirt adhering to the skin surface,
the type of product to be used for the cleansing, and
the cleansing method
The purpose of face cleansers is to remove skin metabolism products, such as
sebum, horny layer flakes, sebum oxidation products and sweat residues adhering
to the skin; dirt and dust from the surrounding air; micro organisms; and in case
of women, makeup products as well (Mitsui, 1997:323). The final formula for the
facial cleanser is given in Table 2.4.

2.5.2

Formulation

Table 2.4 Facial cleanser formula
Activity
Emulsifying agent

INGREDIENTS
4. Cremophor@ A6

% m/m

Cremophor@ A25

1%

Emulsifying agent

Luvitol EHOm

7%

Oil phase of emulsion

Liquid Paraffinm

8%

Oil phase of emulsion

Cetyl alcohol

1.25%

Thickening agent

GMS AISTM

2,5%

Co-emulsifying agent

B. Methylparaben

0,3%

Preservative

0.2%

Preservative

2%

Moisturiser

1%

Propylparahen
Propylene Glycol
Sodium lactate
Urea
Distilled water

I
II

5%

5%
to 100%

I

I Stabiliser
I Active (moisturiser)
I

Solvent

2.5.3 Method
Heat phases A and B separately to approximately 80°C. Stir phase A into
phase B and homogenise thoroughly. Cool to room temperature.

2.6 FORMULATION OF A CREAM
2.6.1 Purpose and function of a cream
A cream is a type of emulsion in which two liquids that do not mix together, like
water and oil, are made into a stable dispersion. This is achieved by making the
one liquid the dispersion phase that is dispersed through the other, the dispersion
medium. A lipophilic active ingredient can be dissolved into a water medium
when a cream is used.
The main function of a cream is to maintain the moisture balance, and to keep
the skin moist and supple through the supply of water, humectants and oils
(Mitsui, 1997:341). The final formula for the day cream is given in Table 2.5.

2.6.2 Day cream
2.6.2.1 Formulation
Table 2.5 Formula of a day cream
% mlm

Activity

2%

Emulsifying agent

Cremophor A25@

2%

Emulsifying agent

Luvitol EHOTM

8%

Oil phase of emulsion

Cetyl alcohol

2%

Thickening agent

GMS A/STM

6%

Co-emulsifying agent

0.2%

Glidant

INGREDIENTS

4. Cremophor A6@

Dimethylpolysiloxane

B. Methyl paraben

Preservative

Propyl paraben

Preservative

Propylene glycol

Moisturiser

Vitamin E-acetate

Anti-Oxidant

Urea
Sodium lactate 60%
Distilled water

Active (moisturiser)
Stabiliser
Solvent

2.6.2.2 Method.

Heat phase A and phase B separately to approx. 80'C. Stir phase A into phase B
and homogenise thoroughly. Cool to room temperature.

2.6.3 Foot and heel balm
The final formula for the foot and heel balm is given in Table 2.6.

2.6.3.1 Formulation
Table 2.6 Formula of tl
INGREDIENTS

i. Cremophor A6@

foot and heel balm
% mlm

Activity
Emulsifying agent

Cremophor A25@

Emusifying agent

Liquid Paraffinm

Oil phase of emulsion

Sweet oil

Oil phase of emulsion

Cetyl alcohol

Thickening agent

GMS AISm

Co-emusifying agent

B. Methylparaben

Preservative

Propylparaben

Preservative

Glycerine

Moisturiser

Urea

Active (moisturiser)

Distilled water

Solvent

2.6.3.2 Method
Heat phase A and phase B separately to approximately 80°C. Stir phase A into
phase B and homogenise thoroughly. Cool to room temperature.

2.6.4 Body cream
The final formula for the body cream is given in Table 2.7.

2.6.4.1 Formulation

A. Emulsifying ointment

Oil phase of emulsion

B. Phenoxyethanol

Preservative

C. Urea

Active (moisturiser)

Sodium phosphate

Buffer

Citric acid

Buffer

Distilled water

Solvent

A. Emulsifvinp: ointment
INGREDIENTS

% m/m

Activity

Emulsifying wax

30%

Oil phase for

White soft paraffin

50%

ointment

20%

preparation

Liquid paraffin

@.P, 2000:1766).
2.6.4.2 Method
Heat phase A and phase C separately to approximately 80°C. Mix phase B into
phase A. Stir phase A into phase C and homogenise thoroughly. Cool to room
temperature.

2.7 MATERIALS USED IN THE FORMULATIONS
The materials used

in this study are discussed under the following

classifications: active ingredient, solvents, preservatives and others.

2.7.1 Active ingredient
Table Active ingredient used in formulations
ACTIVE
INGREDIENT
Urea

SUPPLIER

BATCH
NUMBER
1020569

Saarchem (UNIVARB)

2.7.2 Solvents
A solvent must allow the optimum solubility of the solute. Table 2.9 lists all the
solvents that were used in the formulations in this study.

Table Solvents used in formulations
SOLVENT

SUPPLIER

Distilled water

RIIP

Propylene glycol

ACE-Company

Luvitol EHO

BASF

Liquid Paraffin CP

ACECompany

Glycerine

Saarchem (UNIVARB)

Glycerine

Saarchem (UNIVARB)

I

BATCH
NUMBER

2.7.3 Preservatives
Table 2.10 lists all the preservatives that were used in the formulations in this
study.

Table Preservatives used in formulations
SOLVENT

BATCH

SUPPLIER

NUMBER
Labchem Ltd

Ethanol 96%

I

Methylparaben

I

Galderma

El 05025

I

JA 230076

Propylparaben

Galderma

P 13881

Phenoxyethanol

Sigma

129 H2303

2.7.4 Others
Table 2.1 1 lists all the materials that were used in the formulations in this study,
which are neither preservatives nor solvents.

Table Other materials used in formulations
MATERIAL

SUPPLIER
Sigma

Dimethylpolysiloxane

Cognis LTD

Texapon N70

Saarchem (UNILABB)

Sodium Chloride

Saarchem (Merck Lab)

Sodium Lactate 60%

BASF

Cremophoa RH40
Witch HazelTM

BASF

Cremophor A6TM

BASF

Cremophor A25TM

BASF

Cremophor RH 40TM
Carbopol UltrezTM

BASF

Luvitol EHOTM

Saarchem (UNILABB)

Cetyl Alcohol

CRODA

GMS A/STM

Link Care

Sweet oil

Riedel-de Haien

Citric acid
Sodium Phosphate dihydrate

Saarchem (UNIVARB)

Emulsi WaxTM

Beige Pharm

White soft paraffinTM
EDTA

Saarchem (UNILABB)

Tris(hydroxymethy1)
aminomethane

Saarchem (UNIVARB)

Vitamin E- acetate

BASF

BATCH NUMBER

2.8 CONCLUSION
Each of the final formulations were prepared in sufficient quantities and
stored at different temperatures during stability testing.
Chapter 3 discusses the stability testing that was performed on these newly
formulated products developed in this study. The goal of the stability testing
is the selection of the most stable dosage form. Formulators will attempt
different formulas, and comparing their stability is one criterion for formula
selection (Carstensen, 1990:12).

CHAPTER 3

STABILITY TESTING

3.1 INTRODUCTION
Stability testing may be defined as the process of evaluating a product to ensure
that key attributes stay within acceptable limits. In order to make this testing
meaningful, it is important to accurately establish the nature of these critical
product attributes, to make sure how they change over time, and to define what
degree of change is considered acceptable.
Stability data are useful as an "early warning system" that can alert the chemist
to potential formulation/package-related problems. Such advance information
can be helpful in many ways (Romanowski & Schueller, 2001:769).
More than other products, cosmetics are intended to be aesthetically pleasing to
the consumer. For this reason consumers are likely to notice subtle changes in
the odour or appearance of their favourite products. Since no product remains

100% unchanged as it ages, it is critical that the chemist anticipates the changes
that may occur and make sure that they stay within limits that are acceptable.
Studying the performance of samples that are exposed to accelerated aging
allows assessment of how the product will function over time. This is
particularly important for cosmetic products intended to deliver "active"
ingredients. If the formula is not stable, the delivery of the active ingredient may

be impaired. Properly designed stability testing can reveal such problems so that
corrective action can be taken (Romanowski & Schueller, 2001:770).

.

Most companies have standardised test procedures for the storage of stability
samples which depend on the objective of the study. Such procedures involve
evaluations of samples stored at a variety of conditions and include enough
samples to be statistically significant. Usually storage is done at elevated
temperatures, under freeze andlor freeze thaw cycles and exposure to various
types of light. Elevated temperature storage is critical, since the rate of chemical
reactions roughly doubles for every 10°C increase in temperature. Storage at
higher temperature allows acceleration of the aging process and certain problems
are detected much sooner than they would appear at room temperature. Of
course, the potential drawback is that, at high temperatures, reactions are forced
to occur that would not happen at all at lower temperatures. The most common
storage conditions used in the cosmetic industry are 54°C or 50°C, 45°C 37°C or
3 5 T , room temperature (25OC), 4°C. freezelthaw (Romanowski & Schueller,
2001:772).
Since many of the tests that must be conducted to evaluate product performance
will affect the sample physically, multiple samples are required at each storage
condition to ensure there will be enough samples left for evaluation at the end of
the test period (Romanowski & Schueller, 2001:772).

3.2 STABILITY PROGRAM
Seven different cosmetic products were formulated: hair gel, shampoo, facial
toner, facial cleanser, day cream, foot and heel balm and body cream. The
formulations were tested under ICH conditions (ICH, 2003:4) over a period of
three months at three different storage, temperatures. Stability indicating tests
that applied to these formulations, were conducted.


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