HERBAL COMPOSITION WITH ANTIFUNGAL NANOEMULSION SPRAY FOR SUSTAINED RELEASE

Abstract

HERBAL COMPOSITION WITH ANTIFUNGAL NANOEMULSION SPRAY FOR SUSTAINED RELEASE The present invention provides a herbal antifungal nano emulsion spray composition, comprising Mela/euca a/ternifolia leaves extract, Azadirachta indica dried seeds and fruits extract, Curcuma tonga rhizome extract, Centella asiatica herb extract, Aloe barbadensis leaves extracts, Avena sativa grains extract; Coconut oil, Emulsifier, Humectarit and Suspending agent; wherein the ratio of Melaleuca alternifolia leaves extract, Azadirachta indica dried seeds and fruits extract, Curcuma /onga rhizome extract, Centella asiatica herb extract, Aloe barbadensis leaves extracts, Avena sativa grains extract in coconut oil is l: l: l: I: l: I ratio. The present invention also provides a process for preparing an herbal antifungal nanoemulsion spray composition

Specification

FIELD OF THE INVENTION
The present invention relates to an herbal composition with antifungal
nanoemulsion spray for sustained release.
BACK GROUND OF THE INVENTION
Nanoemulsion antifungal spray is a topical spray of a liquid or solid formulation is
converted into a dynamic mixture dispersed in gas through automation.
Nanoemulsion antifungal spray are dispersions of nanosize droplets in continuous
phase. They can be used to solubilize various hydrophobic and hydrophilic
substances that originally have low solubility in the continuous phases.
Nanoemulsion used for cosmetic formulations are mostly oil-in-water type.
Tea tree oil:
The scientific name for Tea tree oil is Melaleuca alternifolia and family name is
Myrtle. Tea tree oil, tea tree, Australian tea tree oil, tea tree essential oil, Melaleuca
oil. Tea tree oil comes from steam distillation of the leaves of the tea tree. The tea
tree grows on the swampy southeast coast of Australia. The aboriginal people of
Australia have traditionally used tea tree oil as an antiseptic (germ killer) and herbal
medicine. Today, external use of tea tree oil is promoted for various conditions such
as acne, athlete's foot, lice, nail fungus, cuts, mite infection at the base of the
eyelids, and insect bites [I].
Neem oil:
Neem oil scientific name is Azadirachta indicia is fast-growing tree of the
mahogany family is (Meliaceae), valued as a medicinal plant, as a source of organic
pesticides, and for its timber. Neem is likely native to the Indian subcontinent and to dry areas throughout South Asia. Nearly all parts of the Neem tree are useful,
and many of its medicinal and cosmetic uses are based on its antibacterial and
antifungal properties. Neem IS commonly used m shampoos for
treating dandruff and in soaps or creams for skin conditions such as acne, psoriasis,
and athlete's foot. Neem oil can kill soft-bodied insects on contact and decreases
mating and reproductive behaviors, reducing pest fecundity. As a fungicide, neem
oil is used to control rust, black spot, mildew, scab, anthracnose, and blight [2].



Turmeric oil:
Turmeric is a common spice that comes from Curcuma longa and family, name is Zingiberaceae It constains a chemical called curcumin which might reduce swelling. Turmeric has a warm bitter taste and is frequently used to flavor or color curry powders mustards, butters and cheeses. Because curcumin and other chemicals in turmeric might decrease swelling, it is often used to treat conditions that involve pain and inflammation. People commonly use turmeric for ostearthitis. It also used for hay fever, depression, high cholesterol a type of liver disease and itching, but there is no good scientific evidence to support most of these uses. There also no good evidence to support using turmeric for COVID 19 Dont't confuse turmeric with Javanese turmeric root or tree turmeric. Also don't confuse it with zedoary or goldenseal which arwe unrelated plants that are sometimes called turmeric[3].

Gotu kola:
Gotu kola scientific name is Centella asiatica is an herb in the parsley. It has a long history of use in the traditional Chinese and Ayurveda medicine systems Gotu kola contains certain chemicals that seem to decrease swelling and blood presure. It also seems to increase collagen produciton which might be helpful for wound healing People use GOtu kola for burns abd poor circulation that can lead to varicose veins. It is also used for scars, stretch marks, and many other conditions but there is no good scientific evidence to support most of these uses[4].

Aloe vera:
Aloe vera scientific name is Aloe harhadensis miller. It belongs to Asphodelaceae
family. Aloe is a cactus-li~e plant that grows in hot, dry climates. It is cultivated in
subtropical regions around the world, including the southern border areas of Texas,
New Mexico, Arizona, and California. Historically, aloe has been used for skin
conditions and was thought to improve baldness and promote wound healing. Aloe
is-used topically (applied to the skin) and orally. Topical use of-aloe is promoted
for acne, lichen planus (a very itchy rash on the skin or in the mouth), oral .
submucous fibrosis, burning mouth syndrome, bums, and radiation-induced skin
toxicity. Oral use of aloe is promoted for weight loss, diabetes, hepatitis, and
inflammatory bowel disease [5].
Oat extract.
Oat straw comes from the unripened Avena sativa plant, and family name is
Poaceae. Which is commonly grown in Northern Europe and North America. As
an extract, oat straw is often sold as a tincture but can also be found in powder and
capsule form. It's believed to offer numerous health benefits, such as reduced
inflammation and improved brain function and mood. It is high in iron, manganese,
and zinc, though its nutrient composition can vary by brand. The extract is claimed to offer many health benefits, including improvements in brain health, insomnia,
stress, and physical and sexual performance. However, not all of these benefits are
supported by research [ 6].
Honey:
Honey is a sweet and viscous substance made by several species of bees, the bestknown
of which are honey bees. Honey is a syrupy liquid that honeybees make
from plant nectar. It is a common ingredient in many foods and is available in many
forms. The product also has several potential health benetits and plays a role in
many home remedies and alternative medicine treatments. Rich in antioxidants,
Better for blood sugar levels than regular sugar, May improve heart health,
Promotes bum and wound healing, May help suppress coughing in children, Easy
to add to your diet [7].
Coconut tree:
Coconut tree scientific name is Cocos nucifera (L) and family name is Arecaceae.
Coconut is a tree in the palm, found in moist, tropical climates. Trees grow up to
30 meters tall, with large feather-like leaves and smooth trunks. Coconuts are
commonly grown in tropical countries, and are particularly suited to small-scale
production where they can be combined with other crops such as cassava, yams,
sweet potatoes, bananas and pineapples. The fruit or 'drupe' of the tree is notable
for its heavy protection, high water content and oil-rich flesh. The husk, shell, flesh,
oil and milk of the coconut all have useful applications and a rich history of use for
cooking, soap-making, cosmetics, religious rituals and furniture making in many different cultures. Coconut oil can be produced by first drying the flesh usmg
sunlight or kilns [8].
OBJECTS OF THE INVENTION
The main object of the present invention is to provide topical anti-fungal
nanoemulsion spray, comprising, Melaleuca alternifolia leaves extract,
Azadirachta indica dried seeds and fruits extract, Curcuma Zanga rhizome extract,
Centella asiatica herb extract, Aloe barbadensis leaves extracts, Avena sativa
grains extract, coconut oil and emulsifiers, humectant and suspending agent.
Another object of the present invention is to provide antifungal nanoemulsion spray
composition, comprising, Melaleuca alternifolia leaves extract, Azadirachta indica
dried seeds and fruits extract, Curcuma longa rhizome extract, Centella asiatica
herb extract, Aloe barbadensis leaves extracts,Avena sativa grains extract, coconut
oil and emulsifiers, humectant and suspending agent with effective antifungal
activity.
Still, another object of the present invention is to provide a process for the
preparation of an herbal potent antifungal nanoemulsion spray composition,
comprising, Melaleuca alternifolia leaves extract, Azadirachta indica dried seeds
and fruits extract, Curcuma Zanga rhizome extract, Centella asiatica herb extract,
Aloe barbadensis leaves extracts, Avena sativa grains extract, coconut oil and
emulsifiers, humectant and suspending agent.
SUMMARY OF THE INVENTION
Accordingly, the present invention provides anti-fungal nanoemulsion spray
composition which comprises, Melaleuca alternifolia leaves extract, Azadirachta
indica dried seeds and fruits extract, Curcuma Zanga rhizome extract, Centella
asiatica herb extract, Aloe barbadensis leaves extracts, Avena sativa grains extract,
coconut oil and emulsifiers, humectant and suspending agent.
In an embodiment of the present invention, Melaleuca alternifolia leaves extract,
Azadirachta indica dried seeds and fruits extract, Curcuma longa rhizome extract, Centel/a asiatica herb extract, Aloe barbadensis leaves extracts, Avena sativa
grains extract, in antifungal nanoemulsion spray composition is I: I: I: I: I: I ratio.
The present invention also relates to a process for the preparation of anti-fungal
nanoemulsion spray herbal composition, which comprises, steeping Melaleuca
alternifolia leaves extract, Azadirachta indica dried seeds and fruits extract,
Curcuma longa rhizome extract, Centella asiatica herb extract, Aloe barbadensis
leaves extracts, Avena sativa grains extract in coconut oil for 15 minutes at a
temperature of 80°C; adding emulsifier to the mixture; blending mixture in
homogenizer to form homogenous solution of oil and extracts; wherein the ratio of
Melaleuca alternifolia leaves extract, Azadirachta indica dried seeds and fruits
extract, Curcuma longa 'rhizome extract, Centel/a asiatica herb extract, A lne
barbadensis leaves extracts, Avena sativa grains extract in coconut oil is I: I: I: I: I: I
ratio.
Brief Description of drawings
In the drawings accompanying the specification, Figure I shows
In the drawings accompanying the specification, Figure 2 shows
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a herbal antifungal nanoemulsion spray
composition, which comprises Melaleuca alternifolia leaves extract, Azadirachta
indica dried seeds and fruits extract, Curcuma longa rhizome extract, Centella
asiatica herb extract, Aloe barbadensis leaves extracts, Avena sativa grains extract,
coconut oil and emulsifiers, humectant and suspending agent; Where in the ratio of
Melaleuca alternifolia leaves extract, Azadirachta indica dried seeds and fruits extract, Curcuma longa rhizome extract, Centella asiatica herb extract, Aloe
barbadensis leaves extracts, Avena sativa grains extract in coconut oil is I: I: I: I: I: I
ratio.
The present invention also relates to a process for the preparation of anti-fungal
nanoemulsion spray composition, which compnses, steeping Melaleuca
alternifolia leaves extract, Azadirachta indica dried seeds and fruits extract,
Curcuma longa rhizome extract, Centella asiatica herb extract, Aloe barbadensis
leaves extracts, Avena sativa grains extract in coconut oil for 15 minutes at a
temperature of 80°C; adding emulsifier to the mixture; blending mixture in
homogenizer to form homogenous solution of oil and extracts; wherein the ratio of
Melaleuca-alternifolia leaves extract, Azadirachta indica dried seeds and fruits
extract, Curcuma longa rhizome extract, Centella asiatica herb extract, Aloe
barbadensis leaves extracts, Avena sativa grains extract in coconut oil is I: I: I: I: I: I
ratio.





Examples
The following examples are given by way of illustration of the present invention
and therefore should not be construed to limit the scope of the present invention.


Table 1: Formulation ingredients and their properties:






Preparation of extracts:
Tea Tree Oil (Me/a/euca a/ternifolia)
Native to Australia, tea tree oil is obtained from the leaves of the Melaleuca
alternifolia plant through steam distillation. It has been widely used traditionally for
its antibacterial, antiviral ~d antifungal properties [9].
N eem Oil (Azadiracllta indica)
Neem oil is extracted from the seeds and fruits of the neem tree native to India and
other tropical regions in Asia. It is a rich source of triterpenoid compounds like
azadirachtin with potent antifungal activity against dermatophytes and yeasts [I OJ.
Turmeric Oil (Curcuma tonga)
The underground rhizome of the turmeric plant is where turmeric oil is obtained. It
contains volatile oils containing aromatic turmer one and turmerol with anti-
Candida properties [II].
Gotu Kola Extract (Centel/a asiatica)
Gotu kola or pennywort is an Asian herb grown in marshy lands. Its leaves are used
to prepare extracts and contain triterpenoid saponins that promote wound healing
and have mild antifungal effects [12].

Aloe Vera Gel (Aloe barbadensis)
Aloe vera gel obtained from the mucilaginous tissue of aloe vera leaves has been
shown to accelerate wound healing due to its antimicrobial compounds like
anthra.@.inones and polysaccharides [13).
Oat Extract (A vena sativa)
Oat extracts prepared from oat grains contain beta-glucan polysaccharides that
boost immunity and have antifungal properties useful for skin infections.
Probiotic Culture (Lactobacillus aciduphilus, Bifidobacterium lactis,
Lactobacillus rhamnosus)
Probiotic cultures contain beneficial microorganisms that help restore microbial
balance on the skin. The strains Lactobacillus acidophilus, Bifidobacterium /act is
and Lactobacillus rhamnosus have demonstrated ability to inhibit growth of
pathogenic fungi like Candida albicans through production of antifungal
metabolites like organic acids, hydrogen peroxide and bacteriocins.
Coconut Oil (Cocos nucifera)
Coconut oil is extracted from the kernel or inner fruit of mature coconuts. It has
natural properties due to medium-chain triglycerides like lauric acid and capric
acid. These confer antimicrobial effects against dermatophytes and yeasts.
Tween !!0
Tween 80, also known as polysorbate 80, is a non-ionic surfactant commonly used
in pharmaceutical and cosmetic formulations for its emulsifying properties. It helps
stabilize oil-water emulsions and nanoemulsion .



Polyethylene Glycol 400 (PEG 400)
PEG 400 is a hydrophilic non-volatile solvent used in semisolid and liquid
formulations. It acts as a penetration enhancer and emulsifying agent to solubilize
oils in water-based systems.
Glycerin
Glycerin or glycerol is a humectant commonly added to topical products. It helps
retain moisture on the skin s~rrface and enhances skin feeL
Hydroxypropyl methylcellulose (HPMC)
HPMC is a cellulose derivative used as a thickening and suspending agent. It
imparts pseudo plastic rheological properties important for extended drug release
in semisolids.
Purified Water
Purified water acts as the mam solvent and carrier for the aqueous phase of
nanoemulsion. It helps solubilize hydrophilic components and facilitates emulsion
formation.
Selection of excipients:
The topical antifungal spray formula was prepared using Aqueous and non-aqueous
solvents, cosolvents, diluents, permeation enhancers, etc. As a permeation enhancer
Glycerol was used in the preparation.
Selection of spray bottle:
A polymer spray bottle that is nonreactive with the formulation is selected. This
Boston roundspray bottles e is selected and employed with the prepared antifungal nanoemulsion spray formulation. Such bottles are also used for mist spray, spray
for cleaning purposes, sunscreen spray, insect repellents, etc.



Formulation development of antifungal nanoemulsion spray:
Antifungal nanoemulsion spray preparation was developed for use. It is developed
from various natural oils and extracts and some synthetic chemical compounds. It
is made up of 75% Coco'nut oil and the remaining 25% consists of Tea tree oil,
Neem oil, Turmeric oil, Gotu kola extract, Aloe vera gel, Oat extract, Honey, Tween
80, Polyethylene glycol 400 (PEG 400), Glycerin, and purified water. In this
formula, Glycerol is used as the dermal permeation enhancer. All the oils and
extracts used in the formulation are gathered together. Non-oil-based extracts are first mixed together and remaining oil-based ingredients are added to it. For mixing
the oils with extracts the emulsifier agent can be used Hydroxypropyl
methylcellulose (HPMC). Stir this mixture until a homogenous mixture is achieved
after all the ingredients have been combined. After dissolving the Nanoemulsion
solution, it was added to 65% ethyl alcohol and agitated for three hours. Different
amounts of glycerol, water, and 65 % ethyl alcohol were added to the system to
modify its overall volume. This aqueous solution had a concentration of 5 g/L of
nanoemulsion. For the purpose of fully dissolving the nanoemulsion, the entire
solution containing it was swirled for a full hour. Whatmann paper was used to
purify the nanoemulsion solution. Precisely measured nanoemulsion solution was
poured into uniquely shaped bottles and sealed with an atomizer
Characterization of antifungal nanoemulsion spray formulation:
Determination of particle size:
After being diluted I: I 00 in filtered water, the optimized nanoemulsion was
allowed to acclimatize to 25 °C. A Zetasizer Nano ZS dynamic light scattering
device (Malvern Panalytical, UK) with a 4.0 mW laser operating at 633 nm
wavelength was used to measure the particle size. Measurements were made in
triplicate after samples were put onto disposable sized cuvettes. The sampling
period's periodic time was automatically determined. There are three measures
made in the alcoholic solutions.
The efficiency of the pump seal:
The leak test was used to measure the spray pump's efficiency. A pump seal test is
used to examine the spray bottle seal. We evaluated the weight fluctuation of bottles
that were the same size and weight. Prior to and following the test phases, the bottles
are balanced, and the leaks are examined. The pH and evaporation time of the spray
solution are measured by spraying the mixture over ethanol-sensitive paper, which
records the evaporation time of the spray formulation. The digital pH meter was
'
used to estimate the spray formulation's pH value.
Drug content study:
The antifungal spray formulation's medication content analysis is determined by
spectrophotometry. Equation I was used to calculate the drug content at Amax 380
nm using a UV-Visible Spectrophotometer (Shimadzu, Japan, UVPC personal
spectroscopy, software version 2). To put it briefly, 25 ml of buffer solution are mixed with I ml of spray solution. Afterwards, the concentration of the solution's
active medicinal components was measured using spectrophotometry at A.max 380
nm and compared to that of the blank aqueous alcoholic spray.
Concentration of entrapped drug
% Drug content = x 100 -------- Equation I
Total drug concentration
Antifungal spray stability study:
The traditional stability testing techniques are used to conduct this spray stability
investigation. The formulation stability was assessed using the percentage valuation
of the remaining medication discovered. The medication release pattern, rate of
leakage, spray pattern variations in pH, and other factors are also used in the
stability study.
In-vitro skin permeation' study of the topical antifungal spray:
Before initiating skin irritation research, the faculty of pharmacology at QIS
College of Pharmacy, Ongole, Andhra Pradesh, provided approval to the
Institutional Animal Ethical Committee. The male rat skin weighing 150 ± 25 g was
used for the in vitro investigation of the antifungal spray formulation's penetration
into the skin. The rat was first slaughtered and then its skin was removed by placing
it on a Franz diffusion cell with a surface area of7.0 cm2.The citrate buffer with pH
6 at 3 7 oc was used as the dissolving medi\lffi. This buffer solution is added to I ml
of spray solution to make 25 mi. Afterwards, the concentration of the solution's
active medicinal compont;nts was measured using spectrophotometry at Amax 380
nm and compared to that of the blank aqueous alcoholic spray. This skin penetration
investigation is conducted six times a year on an average. Following the investigation, a time-plot was created usmg the percentage of medicines that
entered the body. The slope was used to compute the flow for the aforementioned
investigation. Using Fick's first rule of diffusion, which is represented by the
following equation, the skin permeability (Kp) of the topical antifungal spray
formulation across ways rat skin was determined.
Skin permeability (Kp) = f ------------------------equation 2
Where; j is the flux (mg/cm2 !h) and C is the drug concentration in the donor
compartment
Antifungal activity study:
The antifungal nanoemulsion spray was investigated using the fungal strains. In this
inquiry, the diffusion approaches of Minimum Bacterial Concentration (MBC) and
Minimum Inhibitory Concentration (MIC) can be advantageous. This has 4 mm of
depth and 125-150 mm of Sabourad dextrose agar medium added to it The aseptic
approach was used, and the pH range used was 6.2 to 6.4. The surplus fluid was
removed from the broth culture of a particular organism by spinning the sterile swab
after it was inserted. Uniform growth can be obtained by rotating the plate at 90%
and streaking it in one direr.tion. After that, these plates are permitted to dry for
around five minutes. Each of these plates was incubated at 3 7 oc (98.6°F)
throughout the entire night These antifungal spray formulations' inhibition zones
were compared with the conventional formulations.



Spray formula:
This formula consists of 75 % ethyl alcohol and the remaining 25 % of the active
natural ingredients. The optimized formula was selected based on the solution
transparency, rate of dehydration, and more. Formulation I, Fo was just the drug
solution which only consisted of ethyl alcohol this showed the high clarity with a
high concentration of the ethyl alcohol. The formulation, Fo was found to be
transparent. The organic solvents used in the spray formulation have a high
vaporization rate so they evaporate rapidly leaving behind a thin coating of AP!s
on the skin this last for 4 hours. By comparing the formulations Fo, F1, and F2 found
that these are better than other spray formulations. Formulations Fo and F2 showed
a zero-order kinetic model while formulation F 1 showed root time kinetics with an
R2 value of0.9608. Formulations F1 and F2 (containing film formers and penetration
enhancers) showed more flux and Q24 value for the drug as compared to
Formulation Fo. The spray displays affect by the shape and size of the orifice of the
spray nozzle, this is also affected by the pump capacity. All formulation studies
showed good spray displays by giving a uniform, spherical mess. Stability studies,
in terms of the physiochemical parameters the formulated drug preparation showed
good stability. Under normal storage conditions for the formulations, its stability
was found to be intact.




Skin irritation studies:
Irritation was not found significantly on the rat skin specifically the edema and
erythema. The formulation was found to be safe, and nonirritant for transdermal
implementation. This formulation is effective till 24 hours, the results need to be
rechecked by the pharmacokinetic studies.



Antifungal activities: The formulation study proves that the active pharmaceutical
ingredients contain in ti).e formulation are actively antifungal in nature. The
formulation is tested on all species of fungi, it is found that the formulation is
effective against all the species of fungi. All the recorded results suggested the antifungal
activity of nanoemulsion spray even better Itraconazole





ADVANTAGES
The main advantages of the present invention are: when treating topical fungal
infections example like Irritation, Scaly skin, redness, itching, swelling and blisters.
It was discovered that the herbal nanoemulsion spray present invention was more
effective at antifungal activity than the regular from Itraconazole.





We claim,
An herbal antifungal nanoemulsion spray composition, comprising:
a). comprises Melaleuca alternifolia leaves extract, Azadirachta indica dried seeds
and fruits extract, Curcuma longa rhizome extract, Centella asiatica herb extract,
Aloe barbadensis leaves extracts, Avena sativa grains extract.
b). Coconut oil
c). Emulsifier
d). Humectant
e). Suspending agent.
Where in the ratio of Melaleuca alternifolia leaves extract, Azadirachta indica dried
seeds and fruits extract, Curcuma longa rhizome extract, Centella asiatica herb
extract, Aloe ·barbadensis leaves extracts, Avena sativa grains extract in the coconut
oil is l:l:l:l:l:l ratio.
A process for preparmg herbal antifungal nanoemulsion spray composition,
compnsmg:
a). steeping Melaleuca alternifolia leaves extract, Azadirachta indica dried seeds
and fruits extract, Curcu"!a longa rhizome extract, Centella asiatica herb extract,
Aloe barbadensis leaves extracts, Avena sativa grains extract in the coconut oil for
15 minutes at a temperature .:Jf 80°C;
b) adding emulsifier to the mixture of step a);
c) blending mixture of step b) in homogenizer to form homogenous solution of oil
and extracts;
wherein the ratio of Melaleuca alternifolia leaves extract, Azadirachta indica dried
seeds and fruits extract, Curcuma longa rhizome extract, Centella asiatica herb
extract, Aloe barbadensis leaves extracts, Avena sativa grains extract in the coconut
oil is I: l: l: I: I: I ratio.

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