The Evaluation of Shea Butter from butyrospermum parkii as a Vehicle in Sulphur Ointment formulations

Abstract

Background: The need for natural excipients in the formulation of dosage forms is of importance in the development of pharmaceutical industries. Shea butter is a natural fat extracted from the seed of Butyrospermum parkii.

Full text

The Evaluation of Shea Butter from butyrospermum parkii as a Vehicle
in Sulphur Ointment formulations
Mbang N. Femi-Oyewo, Tolulope O. Ajala, Ayodele Mabadeje
Department of Pharmaceutics and Pharmaceutical Technology,
Faculty of Pharmacy, Olabisi Onabanjo University, Ago-Iwoye, Nigeria.
Corresponding Author: Tolulope O. Ajala
E-mail: tolulola1721@gmail.com Phone: +234 802 217 1674
ABSTRACT
Background: The need for natural excipients in the formulation of dosage forms is of importance in the
development of pharmaceutical industries. Shea butter is a natural fat extracted from the seed of
Butyrospermum parkii.
Objectives: The suitability of shea Butter (SB) as a vehicle in the formulation of sulphur ointments was carried
out in comparison with Simple Ointment BP (SO).
Methods: Six ointment formulations (F1-F6) were prepared with SO, SB and a mixture of the two as base.
Formulation with SB as vehicle (F3) was compared with that of SO (F1) and their equal mixture (F5). The effect of
adding 1% cetomacrogol 1000 (a non-ionic surfactant) was studied in F2, F4 and F6. The formulations were
characterized using organoleptic properties, pH, viscosity, drug release, penetration, chemical assay and
stability assessment.
Results: The pH of the formulations was acidic and the values reduce with the addition of surfactant. Ointment
penetration was lower with SO, high with SB and increased with surfactant addition. Formulation viscosities
were high in the order of F3>F1>F2/F4/F6. The drug release in agar increases with time and temperature. Assay
shows acceptable drug content, which was highest in shea Butter.
Conclusion: Shea Butter served as an acceptable vehicle in the preparation of Sulphur ointments giving greater
0
release, higher penetration, better and acceptable drug content and stability at 4 and 25 C.
Key words: Shea butter, sulphur, simple ointment BP, surfactant
West African Journal of Pharmacy (2013) 24 (2)
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West African Journal of Pharmacy (2013) 24 (2) 58-65

RESUME
Contexte : La nécessité d'excipients naturels dans la confection des formes de la dose est importante dans le
développement des industries pharmaceutiques. Le beurre de karité est une graisse naturelle extraite de la
graine dubutyrospermumparkii
Objectifs: La convenance du beurre de karité (BK) comme un véhicule dans la confection d'onguents
sulfuriques a été comparée à celle de l'Onguent Simple BP (OS).
Méthodologie: Nous avons préparé six mixtures d'onguents (F1-F6) en utilisant comme base le OS, le BK, et
unmélange des deux.La mixture utilisant le BK comme véhicule (F3) a été comparée avec celledu OS (F1), et un
mélange égal des deux (F5). Nous avons examiné dans F2, F4 et F6, l'effet produit par l'addition d'un 1% de
cetomacrogol 1000, un surfactant non-ionique. Les mixtures ont été analysées en utilisant les propriétés
organoleptiques,le pH, la viscosité, la diffusion des médicaments, la pénétration, l'essai chimique et
l'évaluation de la stabilité.
Résultats: Le pH des mixtures était acide et les valeurs se sont réduites après l'addition du surfactant. La
pénétration de l'onguent était plus faible avecle OS, élevée avec le BK et elle s'est élevée après l'addition du
surfactant. La viscositédes mixtures était élevée suivant l'ordre de F3>F1>F2/F4/F6. La diffusion
desmédicaments en agar-agar s'accroîten fonction du temps et de la température. L'expérience démontre
une teneur médicinale acceptable qui était au niveau le plus élevé avec le beurre de karité.
Conclusion: Le beurre de karité a servi comme un véhicule acceptable dans la préparation d'onguents
sulfuriques en favorisant une meilleure diffusion, une pénétration plus complète, une meilleure teneur
médicinale plus acceptable et stable à 4 et à 25°C.
Mots clés: Beurre de karité, souffre, onguent simple BP, surfactant
Evaluation du beurre de karité, lebutyrospermumparkii, comme véhicule dans
la confection de l'onguent sulfurique
Correspondante: Tolulope O. Ajala
E-mail: tolulola1721@gmail.com Phone: +234 802 217 1674
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West African Journal of Pharmacy (2013) 24 (2) 58-65

INTRODUCTION
The use of naturally-occurring excipients for
pharmaceutical formulations has been found to be an
1
attractive venture. This is because of economic
advantages, lack of toxicity, ready availability, and
2
possibility of chemical modifications. Plant resources
are renewable especially when cultivated or
3
harvested with methods that are sustainable. Large-
scale processing is easier for preparations that utilize
readily available natural excipients and the prospects
for the development of indigenous pharmaceutical
and cosmetic industries are improved. In addition,
cultural factors encourage the acceptability of
products containing natural substances either as
active ingredients or additives.
Shea butter is a natural fat obtained from the seed
(nuts) of the fruit of the shea tree (Butyrospermum
parkii Kotschy) from the family Sapotaceae, by
crushing, roasting and grinding. It contains many non-
saponifiable components and the following fatty
acids: oleic acid (40-60%), stearic acid (20-50%),
linoleic acid (3-11%), palmitic acid (2-9%), linoleic acid
4
(<1%) and arachidic acid <1%). Shea tree is
indigenous to West Africa and the oil is commercially
5
available in Nigeria. The fat is slightly yellowish or
ivory-coloured and leaves the hands soft and smooth
with no oily traces, in addition to not causing any
5
irritation even with prolonged use. It is useful as a
moisturizer in skin-care preparations and a suggested
6
substitute for conventional fatty vehicles. This is
because of rapid absorption into the skin without
7
greasiness. In Africa, shea butter is used as cooking
oil, waterproofing wax, for hairdressing, for candle-
making, and also as an ingredient in medicinal
ointmen ts . Som e of t he isolate d c hemical
constituents are reported to have anti-inflammatory,
7
emollient and humectant properties.
Sulphur has antibacterial, keratolytic and anti-fungal
8
activity and, when formulated in a suitable ointment
base for topical use, has been known to be a cost-
9
effective and safe anti-microbial agent. Gibsy and
10
Bryant (2000) reported that topical ointment
formulations are less acceptable to patients than
creams owing to their greasiness and garment soiling.
Therefore, the use of shea butter to formulate sulphur
ointments will enhance patient acceptance and
compliance.
The objective of this study is to evaluate the suitability
of shea butter (SB) as a vehicle in the formulation of
sulphur ointments in comparison to simple ointments
BP (SO) and to determine the effect of surfactant on
the formulations.
MATERIALS AND METHODS
Materials
Precipitated sulphur, cetomacrogol 1000 and simple
ointment BP, iodine, acetic acid, sodium sulphide and
formaldehyde solution were of pharmaceutical grades
and obtained from BDH chemicals Ltd. (Poole,
England). Nutrient agar was obtained from Difco
Laboratories (Detroit, USA) while shea butter was
obtained locally from Falawo market in Sagamu, Ogun
State, Nigeria.
Procedure
Identification of Shea Butter
Shea butter was identified by checking the colour,
odour and behaviour during trituration. The melting
point and water absorption capacity were determined
using standard methods.
Preparation of Ointment Formulations
Six formulations (F1-F6) of 300g each were prepared
according to the percentages in Table 1. Each ointment
base (SB, SO or its combination) was melted and a
portion was used in triturating the precipitated
sulphur. The remaining base was gradually added with
constant trituration in a mortar and pestle until a
homogenous product was obtained. The formulation
was transferred into well-labelled ointment jars with
lined caps.
Physicochemical parameters of the formulations The
colour, odour, texture, ease of application, ease of
removal and greasiness were physically assessed.
PH and viscosity determinations
The pH of the cream formulations was measured at
25±2°C using a pH meter (Jenway Model 3520, Essex,
UK). The viscosity of the cream formulations was
carried out with a Brookfield viscometer (VT 181,
Karlsruhe, Germany) at 25±2°C and 37±2°C using
spindle number 1 and the rotational speed of 100 rpm.
Penetration test
Ointment penetration was measured at 25±2°C by
placing the test sample at the base of the
penetrometer (Model No. CXS-2801, Shanghai
Wanilan Equipt Tech Co. Ltd China).The ointment
surface was perpendicular to the vertical axis of the
penetrating object, which is adjusted to touch the
sample surface and then released for ten seconds
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60
Evaluation of shea butter in sulphur ointment

before clamping. Depth of penetration was then
measured in millimeters for each of the formulations
in triplicate.
Release of active ingredient
Nutrient agar was melted, poured and allowed to set
in glass petri dishes. When solid, the surface was
w
flooded with 5% /v ferric chloride solution (Iron III
chloride hexahydrate GR (Merck) and the excess was
drained off until the plates appear dried. Cups were
bored into the agar using #5 cup borer. A little quantity
of each ointment sample was put into broth bottles
and melted in a water bath. The melted samples
(0.25ml) was added using a pipette into a 25ml
volumetric flask and filled to capacity with phosphate
buffer pH6 solution. The volumetric flask was
returned to the water bath for 5 minutes to ensure
adequate diffusion. O.2ml was then placed into the
agar cups in triplicate sampling of each formulation.
Incubation was done at 25 and 37°C and zones of
release shown by colour changes were measured at
varying times of 1-48 hours.
Determination of drug content in formulations
A weighed quantity (0.5g) of each ointment sample in
40mls of distilled water was added to a 2% solution of
sodium sulphite and boiled under reflux condenser
until the sulphur was completely dissolved. It was
cooled, filtered and washed with hot water. The
filtrate and washings were allowed to cool, then re-
filtered and re-washed. A formaldehyde solution of
10ml and 6ml of acetic acid were added and diluted to
150ml with distilled water. Titration was done with
0.1N iodine solution using starch mucilage as an
indicator. One (1ml) of 0.1N iodine solution equates
0.003206g of sulphur.
Determination of stability
Each formulation was packed in airtight containers
and evaluated for its stability by storing at 4°, 25°, 50°
and 75° for 6 months. The colour/odour changes,
texture, and phase separation were evaluated.
Statistical analyses
Data analyses were done using Graph Pad InStat
(Graphpad Software Inc., San Diego, USA). Unpaired
student's t-test and analysis of variance (ANOVA) tests
were utilized. The null hypothesis in each test was that
there were no significant differences between or
within the formulations. P values of <0.05 (i.e 95%
confidence interval) were considered significant.
RESULTS
The shea butter had a melting point of 38.5±2.0°C and a
water absorption capacity of 0.34ml/g. It is ivory-
yellow in colour, hard on standing but softens when
triturated. All ointment samples were non-gritty,
homogenous in colour ranging from yellow to
brownish-yellow having varied luster and gloss. In
addition, they were easy to apply and remove with
soap and water with a ranking of F4>F3>F6>F5>F2>F1.
All formulations having shea butter were more
washable than those without it. The presence of
surfactant also improved the ease of application and
washability.
The physicochemical properties of the ointment
formulations are presented in Table 2. The pH of the
samples was in the acidic region (4.0±0.62-5.8±0.03)
with F1 having significantly higher (p<0.001) value.
Formulations containing the surfactant (F2, F4 and F6)
had lower pH in all cases but the differences were not
significant (p>0.05). The penetration of the ointment
formulations measured within 10 seconds was
4.8±0.41-12.1±1.01mm and reduced when a mixture
of shea butter and Simple Ointment was used as
vehicle in F5 compared to shea butter alone in F3.
Formulations containing surfactant (F2, F4 and F6) had
significantly higher (p<0001) penetration compared to
those containing none (F1, F3 and F5). The viscosity
(>100p) of all samples taken at 25°C was significantly
higher (p<0.001) than those recorded at 37°C (Table 2).
The release of the samples studied in agar showed a
progressive increase in diffusion in relation to time
(Fig.2) and temperature (Table 2). The rate of diffusion
was 0.583-0.646mm/hour showing a prolonged
release profile.
Moreover, the drug content for all formulations
complied with BP (2009) specification of 90-110% at
<1month and after 6months had a decrease of <3%.
Samples stored at 4 and 25°C remained stable for 9
months without phase separation, colour or odour
change while those stored at 50 and 75°C were stable
for only two weeks after which deterioration began.
West African Journal of Pharmacy (2013) 24 (2)
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Mbang N. Femi-Oyewo, Tolulope O. Ajala and Ayodele Mabadeje

Table 1: Details of ingredients in Ointment Formulations
Ingredients
F1 F2 F3 F4
F5 F6
Concentration %w/w
Precipitated
sulphur
10.00
10.00 10 10 10
10
Simple Ointment
BP (SO)
90.00
89.00 - - 45.00
44.50
Cetomacrogol
1000 (CM)
-
1.00 - 1.00 - 1.00
Shea Butter (SB)
-
- 90.00 89.00 45.00
44.50
Total
100.00
100.00 100.00 100.00 100.00
100.00
Formulation
code
pH
Viscosity
(p)
Drug
content (%)
Penetration
(mm)
Release rate
at 25ºC
(mm/hour)
Release rate
at 37ºC
(mm/hour)
F1
5.8±0.03
36±5.31
99.99
7.5±1.02
0.54
0.63
F2
4.8±0.51
41±4.28
97.09
11.9±1.01
0.52
0.58
F3
4.3±0.03
26±2.19
109.48
10.7±0.31
0.54
0.65
F4
4.0±0.62
19±2.09
105.92
12.1±0.81
0.52
0.58
F5
4.5±0.12
15±2.11
108.4
4.8±0.41
0.50
0.56
F6
4.4±0.49
27±3.05
108.5
5.9±0.62
0.52
0.58
0
2
4
6
8
10
12
14
F1 F2 F3 F4 F5 F6
Ointment Penetration (mm)
Ointment Formulations
Key: F1-simple ointment only as base, F2-simple ointment including surfactant as base, F3-shea butter as base,
F4-shea butter including surfactant as base, F5-a mixture of Shea butter and simple ointment in equal quantities as base,
F6- a mixture of Shea butter and simple ointment in equal quantities including surfactant as base
Table 2: Physicochemical Properties of the Ointment Formulations
Figure 1: The effect of surfactant addition on the penetration of Sulphur ointment Formulations
West African Journal of Pharmacy (2013) 24 (2)
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Evaluation of shea butter in sulphur ointment

Key: F1-simple ointment only as base, F2-simple ointment including surfactant as base, F3-shea butter as base,
F4-shea butter including surfactant as base, F5-a mixture of Shea butter and simple ointment in equal quantities as base ,
F6- a mixture of Shea butter and simple ointment in equal quantities including surfactant as base
Figure2: Effect of time on zones of drug release from the ointment bases
DISCUSSION
The water absorption capacity of shea butter is
5
comparable to that noted in the literature and it
shows that the base can be used when absorption
bases a re requ ired in pharmac eutical s kin
preparations. Furthermore, it can aid skin penetration
11
of oil-soluble medicaments . Table 2 shows the
physi cochemi cal propertie s of th e ointment
formulations. The pH is in the acidic region and
compatible with that of the skin (4.0-6.0) hence will
not disturb the normal flora of the skin nor cause
12
irritation. The absorption of ointment formulations
into the skin through the stratum corneum is also
affected by the pH-partition hypothesis and the
fraction of the unionized molecules which crosses
depend on the pH. The ionized molecules have a much
greater aqueous solubility than the unionized, hence
does not penetrate the lipid barrier like the former.
The absorption of the ointment formulations may
therefore be favoured considering the pH
The penetration of the ointment formulations was
appreciable even within ten seconds showing that the
samples can penetrate the dermis, which is the thickest
layer (1-4mm) of the skin, and elicit the therapeutic
activity . The formulation with SB and surfactant gave
the highest penetration showing that when faster
penetration is required, SB mixed with surfactant will
provide a better outcome than a mixture of simple
ointment and shea butter with or without surfactant
which gave significantly lower (p<0.05) values.
Semisolid dosage forms for dermatological drug
therapy are intended to produce desired therapeutic
action at specific sites in the epidermal tissue. A drug's
ability to penetrate the skin's epidermis, dermis, and
subcutaneous fat layers depends on the properties of
the drug and the carrier base. Although some drugs are
meant primarily for surface action on the skin, the
target area for most dermatological disorders lies in the
viable epidermis or upper dermis. Hence, a drug's
diffusive penetration of the skin (percutaneous
West African Journal of Pharmacy (2013) 24 (2)
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Mbang N. Femi-Oyewo, Tolulope O. Ajala and Ayodele Mabadeje

13
absorption) is an important aspect of drug therapy .
Viscosity is the internal resistance to friction involved
in the relative motion of one layer of molecules with
respect to the next due to attractions between
14
molecules . Temperature has been shown to affect
the viscosity of fluids and semisolids in an indirect
relationship described by the Arhenius equation. For
example, the viscosity of liquids decreases by about
14
2% for each degree rise in temperature . The
viscosities of the formulations were high and reduce
when measured using a higher temperature. This
shows that once the ointment comes in contact with
the skin, it will soften and then spread on the surface.
Ointments usually have a high viscosity, which reflects
the adherent property due to their plastic rheologic
behavior that enables their clinging to the skin or
mucous membranes for a protracted period of time to
elicit the intended therapeutic effect. The shape is
retained until an external force is applied and this
property helps to prolong drug delivery at the site of
15
application .
The diffusion rate was less than 1mm per hour
showing the expected prolonged release profile of
semi solids. Likewise, the release of the formulations
was time-dependent (Fig. 2) and might have been
affected by the high viscosity. This could be because
samples with lower viscosity offer less resistance to
the movement of the molecules of active ingredient.
Formulation with only shea butter as base (F3) had the
highest zone of release compared to that with simple
ointment (F1). This could be attributed to the less
greasy nature of SB, which might have enhanced
diffusion within the agar matrix. The release of active
ingredient from ointment bases has been reported to
depend on hydrophilicity or hydrophobicity of the
16
base .
0
The stability of the formulations at 4 and 25 C and not
at higher temperatures agrees with the compendia
specification for storage of semisolid dosage forms. It
also shows that the active ingredient is stable in the
vehicles (simple ointment, shea butter or a mixture of
both) used at these temperatures. Generally,
ointments are expected to be stored in a cool place for
optimal stability to be achieved.
CONCLUSION
Shea butter served as an acceptable vehicle in the
preparation of sulphur ointments giving greater
0
release, higher penetration and stability at 4 and 25 C.
Shea butter can therefore be used in place of Simple
Ointment BP. Furthermore, when high rate of
penetration is required, surfactant addition to both
simple ointment and shea butter is encouraged by
these results.
ACKNOWLEDGEMENTS
The a uth or s her eby a cknow led ge Drugf ield
Pharmaceuticals located in Ota, Ogun State, Nigeria,
for making her laboratory facility available for the
characterization of the samples.
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