TOPICAL COMPOSITION FOR TREATING CORNS AND CALLUSES

Abstract

The present invention relates to a topical composition comprising Calendula officinalis, salicylic acid, urea, optionally benzoyl peroxide, and pharmaceutically acceptable carriers thereof, applied to the affected area of the skin, for the treatment of corns and calluses, are described. The topical composition of the invention incorporates keratolytic, antiinflammatory, and antimicrobial properties of the active ingredients and forms a protective barrier on the site of application for sustained delivery and gradual exfoliation. The present invention also discloses the process for the preparation of topical composition.

Specification

Description:FIELD OF THE INVENTION:
The present invention relates to a topical composition comprising Calendula officinalis,
salicylic acid, urea, optionally benzoyl peroxide, and pharmaceutically acceptable carriers
thereof, applied to the affected area of the skin, for the treatment of corns and calluses. The
present invention also discloses the process for the preparation of topical composition.
BACKGROUND OF THE INVENTION:
Hyperkeratotic tissues, such as: corns (heloma), and calluses (tyloma) are well defined,
thickened lesions of the epidermis. They occur at skin sites that are normally involved in
chronic mechanical stress (corns and calluses). Pain produced by the thickened tissue can
cause these lesions to be debilitating. Thus, corns and calluses are thickened skin layers
developed as a protective response to friction or pressure.
Traditionally, the keratolytic agents have been applied topically to the lesions to solubilize
intercellular bonds resulting in desquamation of the thickened, hyperkeratotic tissues.
Presently, there are many topical formulations existing in the market for the treatment of corns
and calluses, which includes but not limited to creams, gels, corn caps, and paints. However,
there are many problems associated with the existing formulations ranging from multiple
reapplications, does not form barrier and greasy feeling in the application site, requires long
time to dry as thick layer of formulation need to be applied, dose adjustment and wipe off
resistance are not possible, and specifically the corn caps cause skin irritation due to adhesive
material and cannot be used for multiple corns.
Thus, there is a need for the development of new topical composition which causes the faster
relief of corns and calluses, and to overcome the other limitations of the existing marketed
formulations. This is achieved by developing a unique formulation by combining the synthetic
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and natural active ingredients, providing effective treatment for various callosities and
sustained release over time. Additionally, the compositions of the invention can also be used
in the treatment of hyper keratinizing and hyper proliferative skin diseases and conditions
such as ichthyoses, porokeratoses, follicular keratoses, palmoplantar keratodermas, psoriasis,
eczema, dandruff and dry skin.
SUMMARY OF THE INVENTION:
It has been surprisingly discovered that the topical composition of the invention, e.g. the filmforming
solution formulation, offers an advanced method to alleviate discomfort and prevent
complications. This composition incorporates the keratolytic, anti-inflammatory, and
antimicrobial properties of active ingredients and forms a protective barrier at the site of
application for sustained delivery and gradual exfoliation of corns and calluses. The herbal
components e.g. Calendula officinalis extract of the formulation penetrate deeply, offering
soothing relief and reduces inflammation. Additionally, this formulation demonstrated, its
ability to break down the keratin, and broad-spectrum antibacterial activity. This holistic
approach marks a paradigm shift in corns and calluses management, and enhancing the patient
compliance and adherence to treatment.
The present invention relates to a topical composition comprising Calendula officinalis,
salicylic acid, urea, and pharmaceutically acceptable carriers thereof.
In one embodiment of the present invention, the topical composition may also comprise
benzoyl peroxide.
An another embodiment of the present invention the topical composition comprising
Calendula officinalis, Salicylic acid, urea, optionally benzoyl peroxide and pharmaceutically
acceptable carriers thereof.
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In one aspect of this embodiment, the pharmaceutically acceptable carriers include film
forming polymers, plasticizer, solvents and co-solvents thereof.
In another aspect of this embodiment, the solvents are selected from the group consisting of
aqueous solvent or organic solvent or a mixture thereof.
In one embodiment of the present invention the topical composition of the present invention
prepared in the form of solution, preferably the film forming solution.
An another embodiment of the present invention relates to a topical film forming solution
formulation comprising Calendula officinalis, Salicylic acid, urea, optionally benzoyl
peroxide and pharmaceutically acceptable carriers thereof.
In still another embodiment of the present invention relates to the process for the preparation
of film forming solution comprising Calendula officinalis, Salicylic acid, urea, and
pharmaceutically acceptable carriers thereof.
In yet another embodiment of the present invention the film forming solution of the present
invention is used for the treatment of corns and calluses.
The details of one or more embodiments of the invention are set forth herein. Other features,
objects, and advantages of the invention will be apparent from the detailed description, the
examples, and the claims.
DETAILED DESCRIPTION OF THE INVENTION:
Various embodiments and variants of the present invention are described hereinafter.
The articles "a" and "an" are used in this disclosure and may refer to one or more than one
(i.e., to at least one) of the grammatical object of the article. By way of example, "an element"
may mean one element or more than one element.
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The term "and/or" is used in this disclosure to possibly mean either "and" or "or" unless
indicated otherwise.
The term "about", as used herein, when used along with values assigned to certain
measurements and parameters means a variation of up to ±10% from such values, or in case
of a range of values, means a variation of up to ±10% from both the lower and upper limits of
such ranges.
Traditionally, keratolytic agents have been applied topically to the lesions to solubilize
intercellular bonds and removes the stratum corneum of the skin, and/or alters the structure of
the keratin layers of skin resulting in desquamation of the thickened, hyperkeratotic tissues.
Keratolytic agents are used in the treatment of many dermatological disorders, which involve
dry skin, hyperkeratinization (such as psoriasis), skin itching (such as xerosis), acne, rosacea,
corns and calluses. Suitable keratolytic agents include but are not limited to N-acetylcysteine,
azelaic acid, glycolic acid, tartaric acid, salicylic acid, citric acid, lactic acid, pyruvic acid,
gluconic acid, glucuronic acid, malic acid, mandelic acid, oxalic acid, malonic acid, succinic
acid, acetic acid, phenol, resorcinol, retinoic acid, adapalene, trichloroacetic acid, 5-fluoro
uracil, azelaic acid, cresols, dihydroxy benzene compounds, such as resorcinol and
hydroquinone, alpha-hydroxy acids, such as lactic acid and phenol, pyruvic acid, isoretinoic
acid, retinol, retinal, urea and derivatives, esters, salts and mixtures thereof.
Preferred keratolytic agents are selected from the group consisting of salicylic acid, and/or
urea or a combination thereof. In one embodiment of the present invention, the concentration
of keratolytic agents in the topical formulation is therapeutically effective amount to treat the
signs and/or symptoms of corns and calluses. In one aspect this embodiment, the concentration
of salicylic acid present in the range of from about 0.1% to about 10%, preferably from about
0.5% to about 8%, or more preferably from about 1% to about 6.5% of the topical formulation.
Urea has been long recognized for its keratolytic and emollient properties with its ability to
solubilize and denature protein. High concentrations of urea are also known to have a mild,
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antimicrobial effect. Urea further possesses skin exfoliating properties, which are useful in
the control of passage of active ingredients through the dermal barrier. Therefore, in another
aspect of this embodiment, the concentration of urea present in the range of from about 1% to
about 12%, preferably from about 2% to about 10%, or more preferably from about 4% to
about 8% of the topical formulation.
The one or more embodiment of the present invention provides new topical compositions for
the treatment of all kinds of corns and calluses. The compositions of the invention provide for
faster removal of corns, and calluses than do prior art compositions. The compositions of the
invention can also be used in the treatment of other skin disorders including but not limited to
hyper keratinizing and hyper proliferative skin diseases and conditions such as ichthyoses,
porokeratoses, follicular keratoses, palmoplantar keratodermas, psoriasis, eczema, dandruff
and dry skin. The compositions of the present invention comprise one or more active
ingredients can be configured to provide multiple desired effects.
In one aspect of this embodiment, the invention relates to method of treating the corns and
calluses comprises topically administering an effective amount of Calendula officinalis
extract, Salicylic acid, and urea. It is believed that the composition of the invention enhances
diffusion of active ingredients into and possibly through the epidermal and dermal layers of
the skin. It is also understood that the present invention also encompasses a method and
composition for delivery of molecules into the skin.
Calendula officinalis, commonly known as Marigold, is used in the Western and Asian
countries for its keratolytic, anti-inflammatory, and antimicrobial properties. Calendula
officinalis extract is an extract of the calendula (Calendula officinalis) flowers. In some
embodiments, the extract can be an aqueous, alcoholic, or hydro-alcoholic extract. The main
active components of calendula are sesquiterpene and flavonol glycosides, triterpenoid
saponins, triterpene alcohols, flavonoids, carotenoids, xanthophylls, phenolic acids, sterols,
mucilage, tocopherols, calendulin, and bitters. According to some reports, the extract of this
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plant possesses some pharmacological activities which include antioxidant action, keratolytic,
anti-inflammatory, antibacterial, antifungal, and antiviral properties. It was observed that this
plant has cytotoxic effect on tumor cell lines in-vitro and anticancer activity in vivo. Herein
the present invention relates to the topical composition comprising calendula extracts for
treatment and/or reduction and/or prevention of lesions resulted from skin inflammation,
atopic dermatitis, eczema, urticaria, psoriasis, corns and calluses, and skin damage caused by
UV or/radiation therapy. In certain embodiments, the Calendula officinalis extract may be
present in the range of from about 0.5% to about 10% of the topical solution formulation, or
preferably about 1% to about 7%, or more preferably about 2% to about 5% of the topical
formulation.
To obtain a novel treatment that is effective on dermatological disorders in a stable
composition, allowing a single application and utilization that the patient finds pleasant,
encourages to combine benzoyl peroxide, in the same composition because of its
antimicrobial, anti-inflammatory, and anti-oxidant properties. Benzoyl peroxide is an unstable
chemical compound, making it difficult to formulate it in finished products. The efficacy of
benzoyl peroxide is associated with its decomposition when it is placed in contact with the
skin. Specifically, it is the oxidizing properties of the free radicals produced during this
decomposition that lead to the desired effect. Thus, in order to maintain the optimum efficacy
of benzoyl peroxide, it is important to prevent its decomposition before use, i.e., during
storage. The solubility and stability of benzoyl peroxide were studied by Chellquist at al., in
ethanol, propylene glycol and various mixtures of polyethylene glycol and water (Chellquist
E. M. and Gorman W. G., Pharm. Res., 1992, Vol 9: 1341-1346). Benzoyl peroxide is
particularly soluble in polyethylene glycol and ethanol. Preferably the concentration of
benzoyl peroxide in the topical film forming formulation can vary between about 0% to about
5% of the formulation, or more preferably from about 0% to about 4% of the formulation.
The topical composition of the present invention may be prepared in any number of forms,
such as solutions, ointments, creams, salves, impregnated pads, tinctures, liniments, liquids,
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sprays, foams, suspensions, lotions, or patches, preferably solution and more preferably film
forming solution.
In one embodiment of the present invention the topical composition is solution formulation,
preferably film forming solution formulation comprising Calendula officinalis, Salicylic acid,
urea, optionally benzoyl peroxide, and pharmaceutically acceptable carriers thereof.
The topical composition of the present invention contains pharmaceutically acceptable
carriers thereof. The pharmaceutically acceptable carrier delivers the active ingredient to the
site of application. The pharmaceutically acceptable carriers include film forming polymers,
plasticizer, solvents and co-solvents thereof.
The topical film forming solution of the present invention comprising film forming polymers,
produce a stable film in situ after application on the skin or any other body surface. These film
forming polymers can be hydrophobic and/or hydrophilic polymer as basic material for the
preparations. The formed film is sufficiently stable to provide a drug release to the skin from
1 hour to 24 hours. The polymeric solution is applied to the skin as a liquid and forms an
almost invisible film in situ by volatile solvent evaporation.
In one embodiment of the present invention the polymeric film forming solution formulation
provide a modified release of the active ingredients when applied onto the human skin. In
preferred embodiments, the permeation or release of the drug following topical application
from the invention is characterized by a biphasic release profile, the first phase comprising an
immediate release of active ingredients and a subsequent second controlled release phase
comprising release of active ingredients from the film forming solution, upon evaporation of
the solvent system. In the first phase the active ingredients are released either immediately or
after a short time delay to provide a first peak maximum concentration within 30 minutes after
application of the topical solution on the skin, and a second phase of the active ingredients
release is controlled release phase comprising release of active ingredients from the film
forming solution, upon evaporation of the solvent system.
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The film forming polymers are selected from the group consisting of hydrophilic polymer
and/or hydrophobic polymer or a mixture thereof. The hydrophilic polymer may comprise
polyvinyl pyrollidone or a derivative thereof, polyvinyl alcohol, polyvinyl acetate, water
soluble cellulose derivative includes hydroxyl propyl methyl cellulose, hydroxyl propyl
cellulose, hydroxyl ethyl cellulose, dextrans, hyaluronic acid, cyclodextrins, and
polysaccharide polymers such as pullulan, pectin, starch, alginic acid, such as alginates, and
combinations of any of the foregoing. The hydrophobic polymers may include methyl
cellulose, ethyl cellulose, polyisobutylene, silicon gum, microcrystalline cellulose, sodium
carboxyl cellulose, and the like, acrylic polymers or copolymers, methacrylic polymers and
copolymers, including ethoxyethyl methacrylates, cynaoethyl methacrylate, poly(acrylic
acid), poly(methacrylic acid), methacrylic acid alkylamide copolymer, poly(methyl
methacrylate), polymethacrylate, poly(methyl methacrylate) copolymer, polyacrylamide,
aminoalkyl methacrylate copolymer, poly(methacrylic acid anhydride), and glycidyl
methacrylate copolymers. Preferred film-formers includes ethyl cellulose, a non-ionic
copolymer of methyl methacrylate and butyl methacrylate (Plastoid B®), a copolymer of
dimethylamine ethyl methacrylate and a neutral methacrylic acid ester (Eudragit E100®),
ammonio methacrylate copolymer type B (Eudragit RS®), ammonio methacrylate copolymer
type A (Eudragit RL®), methacrylic acid copolymer type A (Eudragit L100®), methacrylic
acid copolymer type B (Eudragit) S100®), and the like. More preferred film forming polymer
is ethyl cellulose. In certain embodiments, the film forming polymer may be present in the
range of from about 3% to about 15% of the topical solution formulation, or preferably about
5% to about 12%, or more preferably about 7% to about 9% of the topical formulation.
The preferred solvent for the film forming solution formulation is polar solvent which includes
ethanol, isopropyl alcohol, n-butanol, methylene chloride, dimethyl ether, water,
hydroalcoholic system alone and/or in combination of two or more solvents. Most preferred
solvent is ethanol. The solvent concentration in the film forming solution formulation can
vary between about 20% to about 70% of the formulation, or preferably from about 30% to
about 65%, or more preferably from about 40% to about 60% of the formulation.
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In another embodiment the co-solvent is selected from the group consisting of acetone,
dimethyl sulfoxide, dimethyl acetamide, glycerin, sorbitol, ethoxyglycol, ethyl acetate,
dipropylene glycol monomethyl ether, methylethyl ketone, glycofurol, ethyl-L-lactate, and a
mixture of at least two of these co-solvents. Indeed, these co-solvents have sufficient volatility
in order to achieve rapid drying of the film forming solution at the site of application, while
improving the solubility of the active ingredients in the presence of the film-forming polymer.
Preferably, the co-solvent of the film-forming solution according to the present invention is
acetone which has proved to be the best co-solvent for solubilizing active ingredients in the
presence of the film-forming polymer. The concentration of co-solvent in the film forming
solution formulation can vary between about 3% to about 30% of the formulation, or
preferably from about 10% to about 28%, or more preferably from about 15% to about 25%
of the formulation.
The film forming solution formulation of present invention also contains plasticizers. The
term plasticizer as used herein refers to a material that, when added to a polymer, imparts an
increase in flexibility, sought transparency, workability, and other properties to the finished
product. The exemplary plasticizer is selected from the group consisting of polyethylene
glycol, diethyl phthalate, phthalic anhydride esters, and esters of adipic acid, epoxidized
esters, triethyl citrate, triacetine, N-methyl-2-pyrrolidone, glycerol formaldehyde, dibutyl
sebacate, diethyl sebacate, dibutyl phthalate, and acetyhriethyl citrate. Preferably, the
plasticizer of the film-forming solution according to the present invention is polyethylene
glycols (PEG), e.g., PEG 300, PEG 400, PEG 600, PEG 800, PEG 1450, PEG 3350, PEG
4000, PEG 5000, and PEG 6000. According to an embodiment of the invention, the
concentration of plasticizer in the film forming solution formulation can vary between about
0.1% to about 6% of the formulation, or preferably from about 1% to about 5%, or more
preferably from about 2% to about 4% of the formulation in addition to the co-solvents
mentioned earlier.
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In applying liquid formulations to the patient in need of such treatment, liquid formulations
are applied, and spread on the affected area of the skin. The formulations of the invention are
to be applied in a therapeutically effective amount. A "therapeutically effective amount"
means any amount which will cause improvement in a disease condition such as removal of
a corns and calluses, when applied to the affected area repeatedly over a period of time. The
amount will vary with the condition being treated and the concentration of the active
ingredients in the formulation being applied. Appropriate amounts in any given instance will
be readily apparent to those skilled in the art by routine experimentation.
The topical film forming formulation of the invention containing Calendula officinalis extract,
there can be additional optional excipients such as wetting agents, preservatives, stabilizers,
lubricants, humectants, permeation enhancer, moisture regulators, foaming agents, binders,
pH regulators, osmotic pressure modifiers, and antioxidants, conventional buffers, perfumes,
emolients, deodorants, and the like.
In one embodiment of the present invention the topical film forming solution formulation
comprising Calendula officinalis extract, salicylic acid, urea, optionally benzoyl peroxide,
and film forming polymer, plasticizer, solvent and/or co-solvent and other excipients thereof.
In another embodiment of the present invention the topical film forming solution formulation
comprising Calendula officinalis extract, salicylic acid, urea, optionally benzoyl peroxide,
ethylcellulose, polyethylene glycol, ethanol and/or acetone.
In yet another embodiment of the present invention the topical film forming solution
formulation comprising about 2% to about 5% of Calendula officinalis extract, about 0.5% to
about 6% of salicylic acid, about 4% to about 8% of urea, about 0% to about 4% of benzoyl
peroxide, about 7% to about 9% of ethylcellulose, about 2% to about 4% of polyethylene
glycol, about 40% to about 60% of ethanol and/or about 15% to about 25% acetone.
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In still another embodiment of the present invention the topical film forming solution
formulation comprising about 3.8% of Calendula officinalis extract, about 1.5% of salicylic
acid, about 6.1% of urea, about 2.7% of benzoyl peroxide, about 7.6% of ethylcellulose, about
2.3% of polyethylene glycol, about 53.3% of ethanol and/or about 22.7% acetone.
In one or more embodiment, the present invention further provides the process for the
preparation of topical film forming solution formulation as described herein. Preferably the
methods comprise first preparing a premix by combining the solvent and co-solvent
approximately in the ratio of about 5:2, and then mixing thoroughly, wherein the solvent is
ethanol and co-solvent is acetone. Followed by the addition of film forming polymer such as
ethylcellulose to the premix, with continuous stirring until achieving a uniform solution to
obtain the mixture. The Calendula officinalis extract solution was prepared separately by
dissolving Calendula officinalis extract in 2 mL of solvent. The prepared Calendula officinalis
extract solution was added to the above mixture, followed by the addition of salicylic acid,
urea, and benzoyl peroxide, with continuous stirring until the complete dissolution of all
components into the solution. The obtained mixture was added with required amount of
plasticizer such as PEG 4000. Mixing is preferably carried out until a substantially
homogenous solution is achieved and all of the components of the formulation have been
incorporated into the film forming solution.
In yet another embodiment of the present invention the topical film forming solution
formulation is configured for augmenting the keratolytic, anti-inflammatory, and
antimicrobial effects and offering rapid relief from many dermatological disorders, and thus
it is used for the treatment of corns and calluses.
In certain embodiments of the presently disclosed topical film forming solution formulations
were subjected to consumer acceptability testing to evaluate the characteristic, effectiveness
and desirability of the product. The topical film forming solution formulation of the present
invention provides many advantages over known, alternate dosage forms such as creams, gels,
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corn caps, and paints. Specifically, it is applicable for easy usage by patients of all age groups,
less number of reapplications as compared to alternate dosage forms such as creams and gels,
forms a barrier over skin surface which leads to improved diffusion of active ingredients at
the site of application, less drying time and greasy feeling as compared to other commercial
dosage forms, wipe off resistance and irritation. It can be applied to the multiple corns unlike
corn caps, and dose adjustment is also possible. It delivers the required dose accurately when
compared to alternate formulation and also provides ultra-rapid onset of action.
The following examples further describe certain specific aspects and embodiments of the
invention and a better understanding of present invention may be obtained through the
following examples and displayed process for manufacturing and it demonstrates the practice
and advantages thereof. It is to be understood that the examples are given by way of
illustration only and are not intended to limit the scope of invention in any manner.
EXAMPLES
Example 1: Topical film forming solution formulation
A topical film forming solution formulations of the invention were prepared. The composition
of these formulations is shown in following Table 1.
Table 1: The composition of topical film forming solution formulations
The topical film forming solution formulations mentioned in Table 1 were prepared by first
preparing a premix comprising ethanol and acetone, approximately in the ratio of about 5:2,
and then mixing thoroughly. The film forming polymer, ethylcellulose was added to the
premix, with continuous stirring until achieving a uniform solution to obtain the mixture. The
Calendula officinalis extract solution was prepared separately by dissolving Calendula
officinalis extract in 2 ml of ethanol. The prepared Calendula officinalis extract solution was
added to the obtained mixture, followed by the addition of accurately weighed amount of
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salicylic acid, urea, and optionally benzoyl peroxide, with continuous stirring until the
complete dissolution of all components into the solution. The obtained mixture was added
with required amount of PEG 4000 and then mixed thoroughly until a substantially
homogenous solution is achieved. The obtained solution is stored in the suitable container.
Example 2: Evaluation of topical film forming solution formulations:
The film forming solution formulations prepared as per example 1 were subjected to various
evaluation studies. All the tests were performed in triplicates.
Example 2a: In-vitro Antibacterial Study
The nutrient agar petri dish plates were prepared according to the standard instructions. The
McFarland standard solution was prepared and used to standardize the approximate number
of bacteria in a liquid suspension by comparing the turbidity of the test suspension with that
of the McFarland Standard. The bacterial strains such as Escherichia coli, Pseudomonas
aeruginosa, Staphylococcus aureus and Bacillus subtilis were prepared and cultured in the
growth media until reaching the desired growth phase. The prepared agar plates were
S.
No.
Ingredients Concentration (% w/v)
Formulation
1 (F1)
Formulation
2 (F2)
Formulation
3 (F3)
Formulation
4 (F4)
1. Calendula officinalis 3.9 3.8 3.7 3.6
2. Salicylic acid 1.6 1.5 6.1 5.8
3. Benzoyl peroxide - 2.7 - 2.6
4. Urea 6.3 6.1 5.9 5.8
5. Ethylcellulose 7.8 7.6 7.5 7.3
6. PEG 4000 2.3 2.3 2.2 2.2
7. Acetone 23.4 22.7 22.4 21.8
8. Ethanol 54.7 53.3 52.2 50.9
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inoculated with the test bacterial strains to form a uniform lawn of growth and then wells were
created at equidistant points on the agar plate. The formulations of the invention and the
reference standards were prepared in desired concentrations to be tested, added into the wells
by using a sterile pipette and then incubated at appropriate temperatures for 24 hours to 48
hours. Simultaneously the controls were also maintained for comparison. The diameter of
observed zones of inhibitions were measured in millimeter (mm) by using a ruler as shown in
Table 2.
Table 2: Zone of inhibition (mm) of topical film forming solution formulations and reference
standard against various bacterial strains
In an in-vitro study it was revealed that all the topical formulations had shown inhibition
against Bacillus subtilis, Escherichia coli, Staphylococcus aureus, as well as Pseudomonas
aeruginosa, as shown in Table 2. However, F2 formulation had shown the better or
comparable antibacterial effect than the reference standards such as Corn caps, and Dr foot
against all bacterial strains tested.
Example 2b: Anti-inflammatory Activity
The Croton oil ear test was performed to evaluate the anti-inflammatory activity of the film
forming solution formulation of the invention. Cutaneous inflammation was induced by
applying 15μl of a solution of croton oil in acetone to the inner surface of the right ear of male
Albino Swiss mice (Charles River, Italy) weighing 28-32 g, anaesthetized with ketamine-HC1
Bacterial stains
Zone of Inhibition (mm)
F1 F2 F3 F4 Corn caps Dr Foot
Bacillus subtilis 23 35 29 33 16 24
Escherichia coli 23 35 21 27 14 21
Staphylococcus aureus 20 27.5 31 30 10 27
Pseudomonas aeruginosa 22 32.5 33 33 19 17
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(150 mg/kg intraperitoneally). The other ear remained untreated since preliminary
experiments had shown that acetone did not affect ear plug weight (EPW). The controlateral
ear remained untreated since the drugs dissolved in acetone did not affect the EPW. The antiinflammatory
drugs diclofenac was dissolved in the inflammation-inducing solution. Six
hours later, the animals were killed by cervical dislocation and a plug (6 mm in diameter) was
removed from both the treated and the untreated ear. The percentage anti-inflammatory
response was monitored by measuring the differences in weight as a measure of the edematous
response between the two ear plugs as an index of the overall process as shown in Table 3. At
least two experimental groups of seven animals were used for each tested formulations.
Table 3: Anti-inflammatory activity of topical film forming solution formulations and
standard diclofenac
Notably, the anti-inflammatory activity all the formulations of the invention were comparable
or better than that of reference standard diclofenac. Specifically, the F2 formulation had
shown better anti-inflammatory effect than other formulations of the inventions as well as
reference standard diclofenac.
Example 2c: Keratolytic Activity
Formulations % Anti-inflammatory activity
F1 91
F2 92.25
F3 75
F4 70.54
Diclofenac 75
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The film forming solution formulations of the present invention were subjected to the
keratolytic activity and compared with the reference standards such as Dr foot, Corn caps, and
Salactin. The percentage keratolytic activity of all the formulations and reference standards
are mentioned in Table 4.
Table 4: Keratolytic activity of topical film forming solution formulations in comparison with
the commercial products such as Dr foot, Corn caps, & Salactin
Based on the observations from keratolytic activity of the topical film forming solution
formulations of the invention in comparison with the reference standards such as Dr foot,
Corn caps, and Salactin, the F2 formulation had shown better keratolytic activity than other
formulations of the inventions as well as reference standards such as Dr foot, Corn caps, and
Salactin.
In consequence of these observations, based on the antimicrobial properties, antiinflammatory,
and keratolytic activity, plus anti-oxidative effects of topical film forming
solution formulation of present invention, it is contemplated that the F2 formulation of the
present invention is useful in the treatment of corns and calluses. Likewise, the formulations
of present invention also may be effective for other skin conditions or disorders for example,
hyper keratinizing and hyper proliferative skin diseases and conditions such as ichthyoses,
porokeratoses, follicular keratoses, palmoplantar keratodermas, psoriasis, eczema, dandruff
Formulation % Keratolytic activity
F1 15.8
F2 96.2
F3 42.6
F4 43.85
Dr foot 5.5
Corn caps 88.1
Salactin 93.3
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and dry skin. Further, these formulations can be applicable in any case of a condition which
involves a secondary skin infection, such as atopic dermatitis and other itching and xerotic
conditions.
Example 2d: In-vitro diffusion study for skin delivery of F2 formulation:
Based on the outcomes of the above in-vitro studies, it is anticipated that the F2 formulation
of the present invention is useful in the treatment of corns and calluses. Therefore, F2
formulation was further subjected to the in-vitro diffusion study to understand the skin
delivery of the formulation. The percentage release of active ingredients from F2 formulation
was measured in frequent intervals for 3 hours as mentioned in Table 5.
Table 5: Percentage release of active ingredients from F2 formulation in 3 hours
Time
(hours)
Percentage release of active ingredients
Calendula officinalis Salicylic acid Urea Benzoyl peroxide
0 0 0 0 0
0.5 0.28 6.65 1.09 15.08
1 0.32 6.66 1.52 15.36
1.5 0.35 7.34 2.31 16.82
2 0.38 7.99 3.30 18.42
2.5 0.46 9.51 4.28 21.43
3 0.53 11.35 5.65 25.44
Notably, following the 3 hours exposure of the F2 formulation through intra-dermal delivery,
the skin penetration profile was observed, which is especially suitable for the treatment corns
and calluses which occurs in the skin and any other skin condition. , Claims:1. A topical film forming solution formulation comprising, Calendula officinalis, Salicylic
acid, urea, optionally benzoyl peroxide and pharmaceutically acceptable carriers thereof.
2. The topical film forming solution formulation according to claim 1, comprising about 2%
to about 5% of Calendula officinalis extract.
3. The topical film forming solution formulation according to claim 1, comprising about 0.5%
to about 6% of salicylic acid.
4. The topical film forming solution formulation according to claim 1, comprising about 4%
to about 8% of urea.
5. The topical film forming solution formulation according to claim 1, comprising about 0%
to about 4% of benzoyl peroxide.
5. The topical film forming solution formulation according to claim 1, wherein the
pharmaceutically acceptable carriers comprising film forming polymer, plasticizer, solvents
and co-solvents thereof.
6. The topical film forming solution formulation according to claim 5, wherein the film
forming polymer selected from the group consisting of polyvinyl alcohol, polyvinyl acetate,
hydroxypropylmethylcellulose, hydroxyl propyl cellulose, hydroxyl ethyl cellulose, methyl
cellulose, ethyl cellulose, microcrystalline cellulose, sodium carboxyl cellulose, dextrans,
hyaluronic acid, cyclodextrins, pullulan, pectin, starch, alginic acid, polyisobutylene, silicon
gum, butyl methacrylate, acrylic polymers or copolymers, methacrylic polymers and
copolymers, or combinations thereof.
7. The topical film forming solution formulation according to claim 6, wherein the film
forming polymer is ethylcellulose in the range of from about 5% to about 12%.
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8. The topical film forming solution formulation according to claim 5, wherein the plasticizer
selected from the group consisting of polyethylene glycol, diethyl phthalate, phthalic
anhydride esters, esters of adipic acid, epoxidized esters, triethyl citrate, triacetine, N-methyl-
2-pyrrolidone, glycerol formaldehyde, dibutyl sebacate, diethyl sebacate, dibutyl phthalate,
and acetyhriethyl citrate.
9. The topical film forming solution formulation according to claim 8, wherein the plasticizer
is polyethylene glycol in the range of from about 2% to about 4%.
10. The topical film forming solution formulation according to claim 5, wherein the solvent
selected from the group consisting of ethanol, isopropyl alcohol, n-butanol, methylene
chloride, dimethyl ether, water, or combinations thereof.
11. The topical film forming solution formulation according to claim 10, wherein the solvent
is ethanol in the range of from about 40% to about 60%.
12. The topical film forming solution formulation according to claim 5, wherein the co-solvent
selected from the group consisting acetone, dimethyl sulfoxide, dimethylacetamide, glycerin,
sorbitol, ethoxyglycol, ethyl acetate, dipropylene glycol monomethyl ether, methylethyl
ketone, glycofurol, ethyl-L-lactate, or combinations thereof.
13. The topical film forming solution formulation according to claim 12, wherein the cosolvent
is acetone in the range of from about 15% to about 25%.
14. A topical film forming solution formulation comprising:
a. about 2% to about 5% of Calendula officinalis extract,
b. about 0.5% to about 6% of salicylic acid,
c. about 4% to about 8% of urea,
d. about 0% to about 4% of benzoyl peroxide,
e. about 7% to about 9% of ethylcellulose,
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f. about 2% to about 4% of polyethylene glycol,
g. about 40% to about 60% of ethanol, and
h. about 15% to about 25% acetone.
15. The topical film forming solution formulation according to claim 14, comprising:
a. about 3.8% of Calendula officinalis extract,
b. about 1.5% of salicylic acid,
c. about 6.1% of urea,
d. about 2.7% of benzoyl peroxide,
e. about 7.6% of ethylcellulose,
f. about 2.3% of polyethylene glycol,
g. about 53.3% of ethanol, and
h. about 22.7% acetone.
16. The process for the preparation of topical film forming solution formulation comprising:
a. preparing a premix by combining the ethanol and acetone with continuous stirring;
b. the film-forming agent, ethyl cellulose introduced into the premix, stirred to obtain
the mixture;
c. mixing the obtained mixture with Calendula officinalis extract solution, salicylic acid,
urea, and optionally benzoyl peroxide with continuous stirring; and
d. mixing the polyethylene glycol to the resulting mixture, and stirred continuously to
obtain the homogenous solution.
17. The topical film forming solution formulation according to any of the preceding claims,
the film forming solution formulation applied to the affected area of the skin, for the treatment
of corns and calluses.

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