SCIENTIFIC CLASSIFICATION
Kingdom:
Plantae
Division:
Magnoliophyta
Class:
Magnoliopsida
Subclass:
Magnoliidae
Order:
Piperales
Family:
Piperaceace
Genus:
Piper L.
Species:
Piper betel L.
DESCRIPTION
Betel
(Piper betle) belongs to the genus Piper of the family
Piperaceae. This plant originates from central and eastern Peninsular Malaysia
and is locally called sirih (Jaganath & Ng 2000). It is distributed
throughout east Africa and the tropical region of Asia. It is a commercial crop
that is widely cultivated in many parts of India and Sri Lanka (Guha 2006).
The
Betel leaf itself has a spicy taste and yields an essential oil widely used as
a medicine. Other biological activities described for the essential oil include
antifungal, antiseptic and anthelmintic effects (Evans, Bowers, and Funk,
1984). It was evident that Betel leaves contained rich carotenes (80 IU/g fresh
wt.), ascorbic acid (1.94 mg/g fresh wt.) and phenolics (Kaur et al., 2010).
Betel
vines are one of the highly investigated plants and phytochemical studies show
that Piper betel contains a wide variety of biologically active compounds whose
concentration depends on the variety of the plant, season and climate. The
aroma of betel leaf is due to the presence of essential oils, consisting of
phenols and terpenes.
1.3 CHEMICAL COMPOUNDS
Betel
vines are one of the highly investigated plants and phytochemical studies show
that Piper betel contains a wide variety of biologically active compounds whose
concentration depends on the variety of the plant, season and climate. The
aroma of betel leaf is due to the presence of essential oils, consisting of
phenols and terpenes.
The
chief constituent of the leaves is a volatile oil varying in chemical
composition from different countries and known as betel oil. The active
ingredient of piper betle oil which is obtained from the leaves are
primary a class of allyl benzene compounds, chavibetol (betelphenol;
3-hydroxy-4-methoxyallylbenzene), Chavicol (p- allyl-phenol; 4-allyl-phenol),
Estragole (p-allylanisole; 4-methoxy-allylbenzene), Eugenol (allylguaiacol;
4-hydroxy-3-methoxyallylbenzene; 2-methoxy-4-allyl-phenol), methyl Eugenol ( Eugenol
methyl ether; 3,-dimethoxy-allylbenzene) and hydroxycatechol
(2,4-dihydroxy-allylbenzene). (Sugumaran M, Suresh Gandhi M, Sankarnarayanan
K, Yokesh M, Poornima M, Sree Rama rajasekhar).
The
extract of betel leaves possesses antimutagenic, anticarcinogenic,
antidiabetic, anti-inflammatory and antibacterial bioactivities (Amonkar et
al. 1986, Padma et al. 1989, Arambewela et al. 2005, Mazura et
al. 2007, Nalina & Rahim 2007). Hydroxychavicol (HC) and eugenol (EU)
are important phytochemicals found in betel leaves. They are reported to
contribute too many bioactivities in betel leaves (Rathee et al. 2006,
Bhattacharya et al. 2007, Mazura et al. 2007, Nalina & Rahim
2007). HC and EU are phenolic compounds which consist of a monocyclic aromatic ring
with an alcoholic, aldehydic or carboxylic group (de Padua et al. 1999).
A. Allylpyrocatechol
The
phenolic constituent allylpyrocatechol from the leaves showed activity against
obligate oral anaerobes responsible for halitosis. The leaf extract also has a
stimulatory effect on pancreatic lipase and antioxidant activity. (Evans,
Bowers, and Funk, 1984).
B. Eugenol
Eugenol,
one of the principal constituent of betel leaf has also been shown to possess
anti-inflammatory effects in various animal models of studies with various
inflamogens (Dohi et al., 1989; Lee et al., 2007). Mechanistic studies with in
vitro systems showed that eugenol blocked the release of the bone resorbing
mediators, including IL-1β, TNF-α, and PGE2 from of LPS-stimulated human
macrophages by suppressing the messenger RNA expression of LPS-induced IL-1β,
TNF-α and COX-2 in macrophages (Lee et al., 2007b). Eugenol suppressed the
COX-2 gene expression in LPS-stimulated mouse macrophage cells (Kim et al.,
2003).
C. Chavibetol
Chavibetol is an organic chemical compound of
the phenylpropanoid class. It is one of the primary
constituents of the essential
oil from
the leaves of the betel plant
(Piper betel). It is an aromatic compound with a spicy odor (de
Padua et al. 1999).
D. Hydroxychavicol
(HC)
The
phenolic compound, Hydroxychavicol, found in the aqueous extract of betel leaf
is reported to exhibit useful bioactivities - anticarcinogenic and
antimutagenic (Amonkar et al. 1986, Padma et al. 1989, Arambewela
et al. 2005, Mazura et al. 2007, Nalina & Rahim 2007).
1.4 MEDICINAL USES
Traditionally,
this edible plant is used for medicinal purposes. Among the documented
traditional medicinal applications, betel leaf is well-known for its use as
masticator or better known as betel quid, which consists of fresh betel leaf,
betel nut, slaked lime paste with or without tobacco. Betel quid chewing acts
as natural tonic and breath refresher to prevent oral malodour (Evans, Bowers,
and Funk, 1984).
Betel
leaves are the most important plant part and are of medicinal, religious and
ceremonial value in Southeast Asia. In India it is customary to serve betel
leaf on various social, cultural and religious occasions and is also offered to
guests as a mark of respect (referred to as tambool) (Warrier et al., 1995).
Based on the color, size, taste and aroma there are many varieties of betel
leaf and some of the most popular Indian varieties are the Magadhi, Venmony,
Mysore, Salem, Calcutta, Banarasi, Kauri, Ghanagete and Bagerhati (Satyavati et
al., 1987; Warrier et al., 1995).
It
is used for other purposes including improving appetite, tonic for brain,
antiseptic for wounds and treatment for diarrhoea. Its promising traditional
applications have led to many chemical and biological studies. The extract of
betel leaves possesses antimutagenic, anticarcinogenic, antidiabetic,
anti-inflammatory and antibacterial bioactivities (Amonkar et al. 1986,
Padma et al. 1989, Arambewela et al. 2005, Mazura et al.
2007, Nalina & Rahim 2007).
The
Betel leaf itself has a spicy taste and yields an essential oil widely used as
a medicine. Other biological activities described for the essential oil include
antifungal, antiseptic and anthelmintic effects (Evans, Bowers, and Funk,
1984).
Medicinally,
the leaves are used in catarrhal and pulmonary infections. The phenolic
constituent allylpyrocatechol from the leaves showed activity against obligate
oral anaerobes responsible for halitosis. The leaf extract also has a
stimulatory effect on pancreatic lipase and antioxidant activity. (Evans,
Bowers, and Funk, 1984).
The
leaves and the stalk of the betel vines have been used since time immemorial to
treat various ailments in Ayurveda, the traditional Indian system of medicine
and also in various folk medicines in Southeast Asia. Chewing betel leaf is
supposed to prevent bad breath (halitosis), improve the vocalization, harden
the gum, conserves the teeth and sweetens breath. The infusion prepared from
the leaves and stems are supposed to be useful in treating indigestion,
bronchitis, constipation, congestion, coughs and asthma. The leaf juice is
given systemically to treat cough and indigestion in children. The Essential
oil isolated from the leaves is supposed to be useful in treating respiratory
catarrhs and as an anti-septic (Chopra et
al., 1982, Satyavati et al.,
1987).
1.5 CREAM
Semisolid
preparation that contains more than one medicinal agents dispersed in either
oil in water or water in oil emulsion with which immiscible is called cream
(Akhtar N et al., 2011). The main
purpose of formulation of cream is to be applied externally on skin. In order
to form monomolecular surfactant film, cream composed of excessive amount of
surfactant at interfaces (British Pharmacopeia).
Oil
in water emulsion is water washable drug base whereas water in oil emulsion
useful for dry skin treatment and also as emollient applications (Piyusha
Deveda et al., 2010). In this modern
era, creams have been used as vehicle for drug delivery to the body. Plants
with specific medicinal properties can be used in this formulation as active
ingredients in order to provide additional value (Akhtar N et al., 2011).
Creams
are mainly applied to the skin due to its advantage of increasing the
solubility and bioavailability of drug substances. Besides, another advantage
of creams is they bypass first pass metabolism and avoid gastrointestinal
environment (Akhtar N et al., 2011).
Cream formulation usually composed of minerals oil such as liquid, soft and
hard paraffins, glycerin and the cetostearyl alcohol. Besides, natural oil
which has nutritional benefits also included in the preparation of such
formulation such as wool fat and bees wax (Florence E Eichie et al., 2010).
Types:
Most
commonly available creams classified on the basis of their function.
- Cleansing & cold cream or lotion
- Vanishing & Foundation cream
- Night & massage cream
- Hand & body cream
- All purpose cream
- Moisturizing cream
1.6 STABILITY OF CREAM
A.
Physical Stability
The
most important consideration with respect to pharmaceutical and cosmetic
emulsions (creams) is the stability of the finished product. The stability of a
pharmaceutical emulsion is characterized by the absence of coalescence of the
internal phase, absence of creaming, and maintenance of elegance with respect
to appearance, odor, color and other physical properties. An emulsion is a
dynamic system, however, any flocculation and resultant creaming represent
potential steps towards complete coalescence of the internal phase. In
pharmaceutical emulsions creaming results as a lack of uniformity of drug
distribution and poses a problem to the pharmaceutical compounder. Another
important factor in the stabilization of emulsions is phase inversion which
involves the change of emulsion type from o/w to w/o or vice versa and is
considered as a case of instability. The four major phenomena associated with the
physical instability of emulsions are flocculation, creaming, coalescence and
breaking (Garti and Aserin 1996, Im-Emsap et al. 2002) (Sinko 2006).
B. Chemical
Stability
The
instability of a drug may lead to the loss of its concentration through a chemical
reaction under normal or stress conditions. This results in a reduction of the potency
and is a well-recognized cause of poor product quality. The degradation of the drug
may make the product esthetically unacceptable if significant changes in color
or odor have occurred. The degradation product may also be a toxic substance.
The various pathways of chemical degradation of a drug depend on the structural
characteristics of the drug and may involve hydrolysis, dehydration,
isomerization and racemization, decarboxylation and elimination, oxidation,
photodegradation, drug-excipients and drug-drug interactions. Factors
determining the chemical stability of drug substances include intrinsic factors
such as molecular structure of the drug itself and environmental factors such
as temperature, light, pH, buffer species, ionic strength, oxygen, moisture,
additives and excipients. (Baertschi and Alsante, 2005; Yoshioka and Stella,
2002; Lachman et al., 1986).
The
chemical stability of individual components within an emulsion system may be
very different from their stability after incorporation into other formulation
types. For example, many unsaturated oils
are prone to oxidation and their degree of exposure to oxygen may be influenced
by factors that affect the extent of molecular dispersion. This could be
particularly troublesome in emulsions because emulsification may introduce air
into the product and because of the high interfacial contact area between the
phases (Barry, 2002).
C. Microbial
Stability
Topical
bases often contain aqueous and oily phases, together with carbohydrates and
proteins and are susceptible to bacterial and fungal attack. Microbial growth
spoils the formulation and is a potential toxic hazard. Therefore, topical
formulations need appropriate preservatives to prevent microbial growth and to
maintain their quality and shelf-life (Barry, 2002; Arger et al., 1996).
Cream formulations may contain fats and oils with high percentage of
unsaturated linkages that are susceptible to oxidation degradation and
development of rancidity. The addition of antioxidants retards oxidation of
fats and oils minimizes changes in color and texture and prevents rancidity in
the formulation.
CHAPTER III
MATERIALS & METHODS
3.1 SOURCES OF SAMPLES
Mature
leaves of Piper betel were collected and used for identification and
authentication of the plants.
3.2 MATERIALS
Piper
betel leaves, Cetyl alcohol, Stearic acid, Methyl paraben, Propyl Paraben,
Glycerin, white bees wax, Potassium Hydroxide, Sodium Hydroxide, Propylene
glycol, Ethanol and distilled water.
3.3 EQUIPMENTS
Soxhlet
apparatus, Brookfield R/S CP Rheometer and Texture Analyser TA.XT plus,
Homogenizer PT 2100, Oven, test tubes, beakers, weighing machine, digital pH
meter, centrifuge tube, centrifuge, glass rod, spatula.
3.4 METHODS
A.
Preparation of the plant leaf extract
The
leaves allow drying and grounded into powder using blender. The dried powder of
piper betel then will be extract with ethanol using the Soxhlet apparatus for
10 hours. The extract was then collected and preserved in desiccators.
B. Preparation
of Cream
In
this study, water in oil emulsion are preparing by adding up of aqueous phase
to the oily phase with continuous agitation. Oil phase comprised of paraffin
oil and surfactant is heat up to 70°C. Aqueous phase comprising of water is
heat to the same temperature and then extract of Piper betle is added in it. After that this is then transfer to the
wax mixture at the same temperature to achieve adequate emulsification. The
cream is then allowed to cool to room temperature (approximately 25°C) with
continuous mixing.
3.5 EVALUATION OF CREAM
A.
Determination of pH
Determination
of various formulated creams is performed by using digital pH meter. It was
measured by direct immersion of the electrode of pH meter in formulated creams.
B. Physical
Analysis
Cream
will be analyze organoleptically (colour, thickness, look, fell) and physically
(creaming and phase separation).
C. Determination
of viscosity
The
viscosity of formulated cream determine by using Brook-field viscosmeter using
spindle S-06 and the test will be conduct in triplicate and the average reading
will be taken.
D. Stability
Tests
Stability
tests are performing at different conditions for cream to note the effect of
these conditions on the storage of emulsion. The test conducted on the
different range of temperature which are 50C, 370C and 600C
for specific period of time.
E. Centrifugation
Tests
Centrifugal
tests are performed for cream immediately after preparation. The centrifugal
tests are repeated for cream after 24 hours, 7 days, 14 days, 21 days, and 28 days
of preparation. The centrifugal tests are performed at 250C and 5000 rpm for 10
minutes by placing 5g of sample in disposable Stoppard centrifugal tubes.
F. Solubility
test
Randomly
mix small amount of formulated cream with water to determine whether creams mix
well with water. Some of the cream will be placed on a slide with a drop of
water. If the creams were not mixed well, it will cause unsmooth particles and
phase conversion will occur where oil in water creams convert to water in oil
creams.
CHAPTER IV
REFFERENCES
1. T.
Nopamart, C. Arinee, K. Watcharee. Antidermatophytic Activity of Piper betle
Cream. Thai J Pharmacol; Vol 28: No.3, 2006.
2. Sugumaran
M, Suresh Gandhi M, Sankarnarayanan K, Yokesh M. Chemical composition and
antimicrobial activity of vellaikodi variety of Piper betle. International
Journal of PharmTech Research. Vol.3, No.4, pp 2135-2139, Oct-Dec 2011.
3. KY
Pin, A Luqman Chuah, A Abdull Rashih, MP Mazura, J Fadzureena, S Vimala &
MA Rasadah. Antioxidant and Anti-inflammatory Activities of Extracts of Betel
Leaves (Piper betle). Journal of Tropical Forest Science 22(4): 448-455 (2010).
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S., Mohana, D.C., Ranhavendra, M.P. and Raveesha, K.A. (2007). Antifungal
activity of some plant extracts against important seed borne pathogens of Aspergillus
sp. Journal of Agricultural Technology 3(1): 109-119.
5. Amonkar
AJ, Nagabhushan M, D’Souza AV, Bhide SV (1991). Hydroxychavicol: a new phenolic
antimutagen from betel leaf. IARC Scientific Publications, 105, 520-4.
6. AA Baravkar1, RN Kale, RN Patil and SD Sawant.
Pharmaceutical and Biological Evaluation of Formulated Cream of Methanolic
Extract of Acacia Nilotica Leaves. Research
J. Pharm. and Tech. 1(4): Oct.-Dec. 2008.
7. R Akhtar, A Naveed.
Anti-aging potential of a cream containing milk thistle extract: Formulation
and in vivo evaluation. African Journal of Biotechnology Vol. 11(6), pp.
1509-1515, 19 January, 2012.
8. B. K. Dwivedi and B.K.Mehta. Chemical investigation
of aliphatic compounds of Piper betle (leaf stalk). J. Nat. Prod. Plant Resour.,
2011, 1 (2): 18-24.
9. K. K. Sharma, R. Saikia, J. Kotoky, J. C. Kalita, J.
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