DESC:FIELD
The present disclosure relates to a topical formulation and a process for its preparation.
DEFINITIONS
As used in the present disclosure, the following terms are generally intended to have the meaning as set forth below, except to the extent that the context in which they are used indicates otherwise.
Topical Formulation: The term “topical formulation” refers to medications/compositions applied directly to the skin.
Heel fissures: The term “heel fissures” refers to cracks or divides in the skin over heels.
BACKGROUND
The background information herein below relates to the present disclosure but is not necessarily prior art.
Heel fissures, commonly known as cracked heels, are a common problem observed in the foot that can cause discomfort and even pain for the individuals. Heel fissures are usually accompanied by thickened skin and occasionally, yellow or brown calluses around the edge of the heel. Heel fissures are usually caused due to dry skin. When weight and pressure are applied to the fat pad under the heel, the heel expands sideways. If the skin is lacking in moisture, it becomes stiff, loses elasticity, and becomes prone to cracking. Other common causes for heel fissures include standing for prolonged periods, obesity, poorly fitting shoes, friction from the back of shoes, incorrect way of walking, and dry and cold weather. Additionally, people suffering from obesity, diabetes, psoriasis, eczema, flat feet, athlete’s foot, fungal infections, heel spurs, hypothyroidism, Sjörgen’s syndrome, and juvenile plantar dermatosis are more likely to have dry skin and are at a greater risk of developing heel fissures.
Usually, the main problem with heel fissures is their appearance. However, in some cases, the condition can be severe if the fissures are deep or if they become infected. This can be painful and some people may even experience bleeding.
The conventionally used treatments for heel fissures include application of an emollient, a humectant moisturizer, an occlusive moisturizer, keratolytic, or other medical treatments such as application of medical glue to seal the cracks, antibiotics (in case of infection), shoe inserts, heel pads or heels cups.
However, most of the conventional treatments need to be administered for prolonged periods and the chances of recurrence of heel fissures are quite high.
Therefore, there is felt a need to provide a topical formulation that mitigates the aforestated drawbacks.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
An object of the present disclosure is to ameliorate one or more problems of the prior art or to at least provide a useful alternative.
Another object of the present disclosure is to provide a topical formulation for alleviating heel fissures.
Yet another object of the present disclosure is to provide a topical formulation for alleviating heel fissures that is effective and provide relief in a comparatively less time.
Still another object of the present disclosure is to provide a simple process for the preparation of a topical formulation.
Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.

SUMMARY
The present disclosure provides a topical formulation for alleviating heel fissures. The formulation comprises extract of Madhuca indica in an amount in the range of 3 % to 15% by weight of the total mass of the formulation; exudate of Shorea robusta in an amount in the range of 5 % to 10 % by weight of the total mass of the formulation; extract of Mentha arvensis in an amount in the range of 0.4 % to 0.7 % by weight of the total mass of the formulation; Jatyadi Taila in an amount in the range of 3 % to 5% by weight of the total mass of the formulation; Tankan Bhasma powder in an amount in the range of 0.7 % to 2.0 % by weight of the total mass of the formulation; at least one excipient in an amount in the range of 15% to 25% by weight of the total mass of the formulation; and a fluid medium in an amount in the range 55 % to 65 % by weight of the total mass of the formulation.

The present disclosure further provides a process for the preparation of the topical formulation.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWING
The method of the present disclosure will now be described with the help of the accompanying drawing, in which:
Figure 1a illustrates the heel fissures observed on the foot of subject 1 at T0;
Figure 1b illustrates the heel fissures observed on the foot of subject 1 at T8;
Figure 1c illustrates the heel fissures observed on the foot of subject 1 at T15;
Figure 2a illustrates the heel fissures observed on the foot of subject 2 at T0;
Figure 2b illustrates the heel fissures observed on the foot of subject 2 at T8; and
Figure 2c illustrates the heel fissures observed on the foot of subject 2 at T15.

DETAILED DESCRIPTION
Embodiments, of the present disclosure, will now be described with reference to the accompanying drawing.
Embodiments are provided so as to thoroughly and fully convey the scope of the present disclosure to the person skilled in the art. Numerous details are set forth, relating to specific components, and methods, to provide a complete understanding of embodiments of the present disclosure. It will be apparent to the person skilled in the art that the details provided in the embodiments should not be construed to limit the scope of the present disclosure. In some embodiments, well-known processes, well-known apparatus structures, and well-known techniques are not described in detail.
The terminology used, in the present disclosure, is only for the purpose of explaining a particular embodiment and such terminology shall not be considered to limit the scope of the present disclosure. As used in the present disclosure, the forms "a,” "an," and "the" may be intended to include the plural forms as well, unless the context clearly suggests otherwise. The terms "comprises," "comprising," “including,” and “having,” are open ended transitional phrases and therefore specify the presence of stated features, integers, steps, operations, elements, modules, units and/or components, but do not forbid the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The particular order of steps disclosed in the method and process of the present disclosure is not to be construed as necessarily requiring their performance as described or illustrated. It is also to be understood that additional or alternative steps may be employed.
As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed elements.
The terms first, second, third, etc., should not be construed to limit the scope of the present disclosure as the aforementioned terms may be only used to distinguish one element, component, region, layer or section from another component, region, layer or section. Terms such as first, second, third, etc., when used herein do not imply a specific sequence or order unless clearly suggested by the present disclosure.
Heel fissures, commonly termed cracked heels, are a condition mainly caused due to dry skin. They can cause discomfort and pain and in severe cases, bleeding. The common remedies to treat heel fissures include the use of emollient, humectant, occlusive moisturizers, keratolytic, liquid bandage, and the like. However, there is felt a need for a topical formulation that can provide quick relief from heel fissures and also gives smooth skin.
The conventional treatments need to be administered for prolonged periods and the chances of recurrence of heel fissures are quite high.
In accordance with an aspect of the present disclosure, there is provided a topical formulation for alleviating heel fissures.
The topical formulation comprises extract of Madhuca indica in an amount in the range of 3 % to 15% by weight of the total mass of the formulation; exudate of Shorea robusta in an amount in the range of 5 % to 10 % by weight of the total mass of the formulation; an extract of Mentha arvensis in an amount in the range of 0.4 % to 0.7 % by weight of the total mass of the formulation; Jatyadi Taila in an amount in the range of 3 % to 5% by weight of the total mass of the formulation; Tankan Bhasma powder in an amount in the range of 0.7 % to 2.0 % by weight of the total mass of the formulation; at least one excipient in an amount in the range of 15% to 25% by weight of the total mass of the formulation; and a fluid medium in an amount in the range 55 % to 65 % by weight of the total mass of the formulation.
The parts of the plants from which the extracts are derived is selected from the group consisting of exudates, roots, shoots, leaves, seeds, bark, aerial parts and fruits.
Madhuca indica (Mahua longifolia) is a forest tree found in central and northern India and Malaysia. It is commonly observed in various parts of the Indian sub-continent, including Bangladesh. Various parts of the tree are used, namely whole young plants, leaves, stems, barks, roots, fruits, flowers, and seeds. Oil extracted from seeds of Madhuca indica possesses skin moisturizing, anti-inflammatory, anti-microbial and wound healing properties. Two proto basic glycosides, namely madhucosides A and B have been isolated from the bark of this tree. Glycosides are also present in seeds of Madhuca indica. Glycosides are known to have wound healing, skin moisturizing and anti-inflammatory activities. These activities may help in healing of the cracked heels.
In one embodiment of the present disclosure, extract of Madhuca indica is oil extract derived from seeds of Madhuca indica. The extract Mahua tree is generally valued for its seeds which have abundant amount of oil bearing capacity. In the present disclosure, the seed oil of Madhuca indica is commercially obtained from Chennai, Tamil Nadu. The saponification value of the seed oil of Madhuca indica is in range of 187 to 197.
Sal Tree or Sarjaras, scientifically known as Shorea robusta, is an evergreen tree growing up to 50 m in height with a cylindrical bole that can be unbranched for up to 25 m and up to 200 cm in diameter. It is native to the Indian Subcontinent and can be found in East Asia. The resin is valued for its use in the treatment of dysentery, gonorrhoea, boils and toothaches. Sarjaras possesses emollient, wound healing and analgesic properties. It protects skin from atmospheric aggressions.
In an embodiment of the present disclosure, the Shorea robusta is exudate derived from the stem of Shorea robusta. In the present disclosure, the exudate of Shorea robusta is obtained commercially from Mumbai, Maharashtra. The resin content in exudate of Shorea robusta is not less than 60%.
Jatyadi Taila is herbal oil used for wound healing in piles, fissure and fistula. It speeds up wound healing processes and results in quick recovery from these diseases. It also reduces itching, irritation and burning in the lesion. Jatyadi oil benefits in open wounds, cuts, burns, abscess, eczema, blisters and non-healing wounds.
The specific gravity of Jatyadi Taila is in the range of 0.90 to 0.92. In the present disclosure, Jatyadi Taila is obtained commercially from Mumbai, Maharashtra.
Tankan Bhasma (Calcined Borax or Suhaga) is an ayurvedic-calcined formulation prepared from borax powder. In Ayurveda, Tankan Bhasma or calcined borax is used for productive cough, breathing problems, wheezing, bronchitis, abdominal pain, dysmenorrhea, dandruff, bad breath and foul-smelling urine. Tankan Bhasma contains borax that plays a role to repair the injuries to the skin and other soft tissues. It heals wound in the shortest time possible, with minimal pain, discomfort, and scarring to the patient.
The borax content in Tankan Bhasma (Calcined Borax or Suhaga) is not less than 80%.
In the present disclosure, Tankan Bhasma is obtained commercially from Kasgannj, Uttar Pradesh.
Pudina Satva is the natural laevo-rotatory menthol obtained from various species of Mentha (Fam. Lamiaceae). Mentha arvensis is the primary species of mint used to make natural menthol crystals and natural menthol flakes. This species is primarily grown in the Uttar Pradesh region in India. Menthol decreases neuronal excitability, therefore contributing to menthol-induced central analgesia; soothes the throat and decongests the respiratory passage. In the formulation of the present disclosure, Pudina Satva provides cold sensations as well as an analgesic effect on the cracked feet. It helps in wound healing by increasing blood flow at application site.
In accordance with an embodiment of the present disclosure, the extract of Mentha arvensis is in the form of crystals. The volatility of the extract of Mentha arvensis is not more than 0.05%. In the present disclosure, Mentha arvensis crystals are obtained commercially from Meerut, Uttar Pradesh.
The excipient is selected from the group consisting of humectant, preservatives, solvent, emulsifiers, stabilizer, anti-oxidant, emollient and fragrance. Other suitable excipients can also be used.
In an embodiment of the present disclosure, the humectant is present in an amount in the range of 4.5 % to 10 % by weight of the total mass of the formulation; a first preservative in an amount in the range of 0.1 % to 0.20 % by weight of the total mass of the formulation; second preservative in an amount in the range of 0.01% to 0.03% by weight of the total mass of the formulation; a first emulsifier in an amount in the range of 4 % to 10 % by weight of the total mass of the formulation; a second emulsifier in an amount in the range of 8 % to 10 % by weight of the total mass of the formulation; a stabilizer/anti-oxidant in an amount in the range of 0.1 % to 0.3 % by weight of the total mass of the formulation; an emollient in an amount in the range of 4 % to 6 % by weight of the total mass of the formulation; a fragrance in an amount in the range of 0.2 % to 0.5 % by weight of the total mass of the formulation; and a solvent in an amount in the range 55 % to 60 % by weight of the total mass of the formulation.
The humectant is selected from the group consisting of propylene glycol, glycerin, alpha hydroxyl acids, glyceryl triacetate, honey and water.
The first preservative is methyl paraben sodium.
The second preservative is propyl paraben sodium.
The first emulsifier is selected from the group consisting of cetostearyl alcohol, glyceryl monostearate, polyglyceryl isostearate, hexyl laurate, and dimethicone.
The second emulsifier is selected from the group consisting of stearic acid.
The stabilizer/anti-oxidant is selected from the group consisting of butylated hydroxytoluene (BHT), disodium edetate, propyl gallate, butylated hydroxyanisole, citric acid, ascorbic acid, and sodium ascorbate.
The emollient is selected from the group consisting of dimethicone, petrolatum, lanolin, and mineral oil.
The fluid medium is water. The formulation of the present disclosure can be prepared in at least one dosage form selected from the group consisting of creams, gels and ointments.
Since the formulation comprises natural ingredients, there are no major side effects on its topical application.
In another aspect of the present disclosure, there is provided a process of preparing the topical formulation for alleviating heel fissures.
At first, the process comprises the steps of preparing an aqueous phase by heating a predetermined amount of water at a temperature in the range of 75 °C to 80 °C followed by adding Tankan Bhasma, a humectant, a first preservative, and a second preservative under stirring to obtain the aqueous phase in the form of a clear solution.
Separately, two oil phases are prepared.
A first oil phase is prepared by mixing Madhuk oil and, Jatyadi oil followed by heating to a temperature in the range of 60 °C to 90°C to obtain an oil mixture. To the oil mixture, exudate of Shorea robusta is added to obtain a second oil mixture followed by adding a first emulsifier and a second emulsifier to said second oil mixture and heating at a temperature in the range of 60 °C to 90°C to obtain the first oil phase.
Separately a second oil phase is prepared by mixing Madhuk oil, Jatyadi oil, Mentha arvensis, and stabilizer under stirring.
The first oil phase is added to the aqueous phase and mixed with continuous homogenization in a vessel to obtain a first homogenous mixture.
An emollient is added in the first homogenous mixture followed by adding the second oil phase under stirring to obtain a second homogenous mixture.
A fragrance is added to the second homogenous mixture to obtain the topical formulation.
The technical advantage in the process of the present disclosure lies in preparation of two oil phases separately.
In general preparation of creams, only one oil phase is present (all oils, waxes are heated and mixed together to prepare an oil phase). However, in the present disclosure, the formulation is prepared in two different parts to get the desired quality and ultimately efficacy of the product. In the preparation of first oil phase, the exudate is mixed with the oil such that the mixing is uniform and the resin particles are distributed uniformly. An improper mixing leads to the cream having gritty particles or lumps.
The foregoing description of the embodiments has been provided for purposes of illustration and is not intended to limit the scope of the present disclosure. Individual components of a particular embodiment are generally not limited to that particular embodiment, but, are interchangeable. Such variations are not to be regarded as a departure from the present disclosure, and all such modifications are considered to be within the scope of the present disclosure.
The present disclosure is further described in light of the following experiments which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure. The following experiments can be scaled up to industrial/commercial scale and the results obtained can be extrapolated to industrial scale.
EXPERIMENTAL DETAILS
Experiment 1: Preparation of the topical formulation in accordance with the present disclosure.
The topical formulation of the present disclosure was prepared by mixing an aqueous phase, first oil phase and second oil phase to obtain the topical cream.
The aqueous phase was prepared by heating water to 75 °C, followed by adding Tankan Bhasma, Propylene Glycol, sodium methyl paraben and sodium propyl paraben under stirring to the aqueous phase in the form of a solution.
Separately preparing a first oil phase by mixing Madhuk oil and Jatyadi oil followed by heating at 75°C to obtain an oil mixture; adding exudate of Shorea robusta to the oil mixture followed by adding cetosteryl alcohol and stearic acid and heating at 75°C to obtain the first oil phase.
Separately preparing a second oil phase by mixing Madhuk oil, Jatyadi oil, Mentha arvensis, butylated hydroxytoluene (BHT) under stirring to obtain the second oil phase.
The aqueous phase was mixed with first oil followed and homogenized to obtain a first homogeneous mixture. The first homogeneous mixture was mixed with dimethicone followed by mixing second oil phase under stirring to obtain a second homogeneous mixture. The homogeneous mixture was cooled to 35 °C followed by adding fragrance and stirred continuously till the topical formulation was obtained with the required consistency.
The concentration of each of the ingredient are provided in below table
Table I
Name Extract/Ingredient Unit Qty (per 100g) %
Madhuca indica Madhuk Oil 5.00 5
Shorea robusta Sarjaras 5.00 5
Mentha arvensis Pudina Satva 0.50 0.5
Jatyadi Taila 4.00 4
Tankan Bhasma 1.00 1
Humectant Propylene Glycol 5.00 5
First preservative Methyl Paraben Sodium BP 0.18 0.18
Second preservative Propyl Paraben Sodium BP 0.02 0.02
First emulsifier Cetostearyl Alcohol 5.50 5.5
Second emulsifier Stearic Acid 9.00 9
Stabilizer/antioxidant BHT 0.20 0.2
Emollient Dimethicone 5.00 5
Fragrance 0.40 0.4
Solvent Water 59.2 59.2

TOTAL 100 100

Experiment 2: Effectiveness of the topical formulation
The topical fomulation was been evaluated for the treatement of heel fissures in two subjects, wherein the formulation was been applied twice a day on the fissures for 15 days. The heel fissures were monitored visually at regular intervals i.e. before start of treatment (T0), after 8 days of application (T8) and after 15 days of application (T15) of the formulation.
It was observed that the subject 1 and subject 2 had both shown visible significant improvement in the appreance of heel fissures after application for 15 days. No side effects of the topical formulation were observed for either of the subjects.
The presence of heel fissures for subject 1 and subject 2 before application of the formulation (T0) is depicted in Figures 1a and 2a, respectively.
The presence of heel fissures for subject 1 and subject 2, after 8 days of the application of the formulation (T8) is depicted in Figures 1b and 2b, respectively.
The presence of heel fissures for subject 1 and subject 2, after 15 days of the application of the formulation (T15) is depicted in Figures 1c and 2c, respectively.
Hence, it was concluded that the topical formulation as disclosed in the present application is effective in treating heel fissures and helps in smoothening the skin.
Experiment 3: Comparative study of efficacy of the topical formulation of the present disclosure vs commercially available topical formulations for alleviating heel fissures.
Effectiveness of the topical formulation of the present disclosure was compared against commercially available topical foot creams.
Study Objectives:
To evaluate efficacy and safety of topical formulation of the present disclosure vs Amarantha Wound Healing Cream and commercially available product (Krack Cream) in subjects suffering from Cracked Heels (Xerosis of the Feet) by assessing number of days required for complete healing / complete clearance of Index cracked Heel
Secondary objectives were to evaluate efficacy of topical formulation of the present disclosure in comparison to Amarantha Wound Healing Cream and commercially available product (Krack Cream) by assessing changes in xerosis assessment scale, changes in skin roughness using graded scale, changes in hyperkeratosis using graded scale, changes in Overall Clinical Cutaneous Score (OCCS), drug compliance at every follow up visits, global assessment of overall change by investigator and subject at the end of the study and changes in tolerability of trial drugs by patient and by physician at the end of the study by assessing adverse events/adverse drug reactions
Study Design:
An Open Labeled, Randomized, Multi-centric, Comparative, Interventional, Prospective, Clinical Study
Number of Visits:
After screening visit/ baseline visit (day 0), all the subjects were called at the study site for follow-up visits in following manner: Visit 1 (Day 7), Visit 2 (Day 14), Visit 3 (Day 21), and Visit 4 (Day 28). If the cracked heel was resolved earlier than this (as per the investigator’s opinion) subject was declared as completed and had to make no more follow up visits.
The composition of the topical formulation of the present disclosure was as follows:
Composition: Each gm Contains:
Sr. Ingredients Botanical Name Part used Quantity % w/w
1. Madhuka Taila Madhuca indica Seed oil 5.0
2. Sarjaras Exudate Shorea robusta Exudate 5.0
3. Jatyadi Taila Ayurvedic Classical Formulation Oil 4.0
4. Tankan Bhasma - Bhasma 1.0
5. Pudina Satva Mentha arvensis Crystals 0.5
6. Excipients, preservatives, water and fragrance, Qs to 100%

Composition of the commercially available product: Each 100 gm of the commercially available product contains

Quath (decoction of herbs) process oil derived from:
Pitadaru, Kampillaka, Pashanbheda, manjistha, Payasvini, Sarjaras
Ghrita, Sasyaka--35.4% w/w
Vrikshamla--3.6% w/w
Base to make --100% w/w
Other approved excipient

Composition of Amarantha wound healing cream: Each gm ccontains:

Sr. No. Ingredients Botanical Name Part used Quantity % (w/w)
1 Jatyadi Taila Generic preparation Oil 4 %
2 Ashvattha Extract Ficus religiosa Stem 3 %
3 Nyagrodha Extract Ficus bengalensis Stem 2 %
4 Mandukaparni Extract Centella asiatica Whole plant 3 %
5 Shala Extract Shorea robusta Exudate 3 %
6 Yashtimadhuka Extract Glycyrrhiza glabra Stem / root 2 %
7 Nimba Extract Azadirachta indica Leaf 1 %
8 Karanja Extract Pongamia glabra Stem / bark 1 %
9 Yashad Bhasma Generic preparation Fine Powder 1.5 %

For the purpose of the investigation, the following inclusion and exclusion criterias were selected.
Inclusion Criteria:
1) Male and female subjects aged 21-65
2) Subjects suffering from moderate to severe xerosis of foot (XAS score > 3 and < 7)
3) Subjects who had not used any moisturizers or keratolytic agents since last week.
4) Subjects willing to make all required study visits
Exclusion Criteria:
1) Subjects having foot lesions (ulcer, skin infection)
2) Subjects with very severe hyperkeratosis requiring chiropody treatment
3) Subjects with skin disorders affecting the foot such as infections (e.g. Athlete’s foot), dermatitis, psoriasis, un-healed skin wounds (including open heel fissures), ulcers or blisters
4) Subjects with systematic disease including peripheral vascular disease or musculoskeletal disorders of the foot or ankle, rheumatoid arthritis or diabetes
5) Subjects having unstable angina pectoris, myocardial infarction, stroke, chronic renal and liver diseases, uncontrolled diabetes mellitus and uncontrolled hypertension.
6) Known cases of HIV/AIDS, Hepatitis C and B, Cancer and major debilitating diseases
7) Known hypersensitivity to ingredients used in study drug
8) Pregnant and lactating women
9) Other conditions, which in the opinion of the investigators, made the patient unsuitable for enrolment or could have interfered with his participation in, and completion of the protocol

Dosage, Study Groups and study duration:
As per randomization list, subjects were allocated to one of the three study groups in 1:1:1 ratio. Subjects were asked to wash their feet with lukewarm water, dry the feet and apply sufficient quantity of given cream twice daily for 28 days or complete healing / complete clearance of Index cracked Heel whichever was earlier.
Results and Observations:
A total of 95 subjects (32 in topical formulation of the present disclosure, 31 in the commercially available product (Krack Cream) group and 32 in Amarantha Wound Healing Cream group suffering from moderate to severe xerosis of feet were recruited in the study. There were no screen failures. Out of 95 recruited subjects, 79 subjects (26 in topical formulation of the present disclosure, 26 in the commercially available product (Krack Cream) group and 27 in Amarantha Wound Healing Cream group completed the study. There were 16 drop outs in the study. In topical formulation of the present disclosure, 6 subjects were dropped out due to drug noncompliance. In the commercially available product, a total of 5 subjects (3 subjects due to drug non-compliance and 2 subjects due to lost to follow ups) were dropped out. In Amarantha Wound Healing Cream group, a total of 5 subjects (4 subjects due to drug non-compliance and 1 subject due to lost to follow up) were dropped out.

Subject Disposition:
Subject Populations topical formulation of the present disclosure Krack Cream group Amarantha Wound Healing Cream group Total
Total no. of cases Enrolled 32 31 32 95
No. of cases Drop Out 06 05 05 16
Reasons for Drop out
Non Compliance 06 03 04 13
Lost to follow Up - 02 01 03
No. of cases Analyzed 26 26 27 79

Primary Outcome:
Comparison of mean duration of days required for healing of Index cracked Heel between the groups:
The mean days required for complete healing of index cracked heel in topical formulation of the present disclosure were 16.69 ± 5.74, in the commercially available product (Krack Cream) group were 22.96 ± 5.76 and in Amarantha Wound Healing Cream group were 25.74 ± 3.37. When compared between the groups, topical formulation of the present disclosure took statistically significant (P < 0.01) less number of days than other groups for healing of cracked heels.
Groups
Mean duration of days required for healing ( ? SD)

topical formulation of the present disclosure (N = 26) *16.69 ± 5.74
Krack Cream group (N = 26) 22.96 ± 5.76
Amarantha Wound Healing Cream group (N = 27) 25.74 ± 3.37
topical formulation of the present disclosure (N = 26) Vs Krack Cream group (P value) P < 0.01
topical formulation of the present disclosure Vs Amarantha Wound Healing Cream group
(P value) P < 0.01
Krack Cream Group Vs Amarantha Wound Healing Cream group
(P value) NS
By ANOVA *Significant NS = Not Significant
Secondary outcomes:
1. Comparison of changes in mean score of xerosis assessment scale between the groups:
When compared between the groups, statistically significant more reduction in mean score of xerosis was observed on all follow up visits in topical formulation of the present disclosure than other two groups. There was no statistically significant difference between the commercially available product (Krack Cream) group and Amarantha Wound Healing Cream group on all visits.
Duration
(Days)
Mean Score of Xerosis ( ? SD)

topical formulation of the present disclosure, (N = 26) Krack Cream (N = 26) Amarantha Wound Healing Cream group (N = 27)
Baseline 5.46 ± 0.81 5.69 ± 0.55 5.48 ± 0.85
7 3.23 ± 1.70 4.58 ± 1.10 4.93 ± 0.96
14 1.50 ± 1.75 3.35 ± 1.92 4.04 ± 1.32
21 0.23 ± 0.59 2.23 ± 2.08 2.96 ± 2.01
28 0.04 ± 0.20 1.73 ± 2.11 2.30 ± 2.22
Mean diff (Baseline –Day 7)
(P value) *-2.23 ± 1.31
(0.001) *-1.12 ± 0.82
(0.001) *-0.56 ± 1.05
(0.03)
Amarantha Footcare Cream Group Vs All groups - *0.002 *0.001
Krack Cream group Vs All - - 0.066 (NS)
Mean diff (Baseline –Day 14)
(P value) *-3.96 ± 1.51
(0.001) *-2.35 ± 1.62
(0.001) *-1.44 ± 1.42
(0.001)
Amarantha Footcare Cream Group Vs All groups - *0.001 *0.001
Krack Cream group Vs All - - 0.059 (NS)
Mean diff (Baseline –Day 21)
(P value) *-5.23 ± 0.91
(0.001) *-3.46 ± 1.84
(0.001) *-2.52 ± 2.21
(0.001)
Amarantha Footcare Cream Group Vs All groups - *0.001 *0.001
Krack Cream group Vs All - - 0.116 (NS)
Mean diff (Baseline –Day 28)
(P value) *-5.42 ± 0.81
(0.001) *-3.96 ± 1.91
(0.001) *-3.19 ± 2.37
(0.001)
Amarantha Footcare Cream Group Vs All groups - *0.004 *0.001
Krack Cream group Vs All groups - - 0.298 (NS)
By Wilcoxon Sign Rank Test *Significant NS = Not Significant
By Mann Whitney U Test

2. Comparison of changes in mean score of skin roughness between the groups:
When compared between the groups, no significant difference was observed between topical formulation of the present disclosure group and the Krack Cream group on day 7, however topical formulation of the present disclosure had shown significantly more reduction in skin roughness score than Amarantha wound healing Cream group on day 7. When compared between the groups, statistically significant more reduction in mean score of skin roughness was observed on day 14 in topical formulation of the present disclosure than other two groups. There was no statistically significant difference between the commercially available product (Krack Cream) group and Amarantha Wound Healing Cream group on all visits. There was no significant difference between any groups on day 21 and day 28.
Duration
(Days)
Mean Score of Skin Roughness ( ? SD)

topical formulation of the present disclosure, (N = 26) Krack Cream group (N = 26) Amarantha Wound Healing Cream group, (N = 27)
Baseline 1.50 ± 0.76 1.54 ± 0.76 1.63 ± 0.63
7 0.77 ± 0.65 1.08 ± 0.74 1.30 ± 0.78
14 0.15 ± 0.46 0.81 ± 0.85 1.07 ± 0.78
21 0.08 ± 0.27 0.35 ± 0.63 0.63 ± 0.74
28 0.00 ± 0.00 0.23 ± 0.43 0.41 ± 0.64
Mean diff (Baseline –Day 7)
(P value) *-0.73 ± 0.60
(0.001) *-0.46 ± 0.58
(0.003) *-0.33 ± 0.55
(0.004)
topical formulation of the present disclosure Vs All groups - 0.144 (NS) *0.026
Krack Cream group Vs All - - 0.379 (NS)
Mean diff (Baseline –Day 14)
(P value) *-1.35 ± 0.80
(0.001) *-0.73 ± 0.87
(0.002) *-0.56 ± 0.58
(0.001)
topical formulation of the present disclosure Vs All groups - *0.020 *0.001
Krack Cream Vs All groups - - 0.689 (NS)
Mean diff (Baseline –Day 21)
(P value) *-1.42 ± 0.76
(0.001) *-1.19 ± 0.90
(0.001) *-1.00 ± 0.78
(0.001)
topical formulation of the present disclosure Vs All groups - 0.424 (NS) 0.064 (NS)
Krack Cream group Vs All - - 0.401 (NS)
Mean diff (Baseline –Day 28)
(P value) *-1.50 ± 0.76
(0.001) *-1.31 ± 0.88
(0.001) *-1.22 ± 0.80
(0.001)
topical formulation of the present disclosure Vs All groups - 0.522 (NS) 0.211 (NS)
Krack Cream group Vs All - - 0.638 (NS)
By Wilcoxon Sign Rank Test *Significant NS = Not Significant
By Mann Whitney U Test

3. Comparison of changes in mean score of hyperkeratosis between the groups:
When compared between the groups, no statistically significant difference was observed on all follow up visits.
Duration
(Days)
Mean Score of Hyperkeratosis ( ? SD)

topical formulation of the present disclosure, (N = 26) Krack Cream (N = 26) Amarantha Wound Healing Cream group, (N = 27)
Baseline 0.04 ± 0.20 0.08 ± 0.27 0.07 ± 0.27
7 0.00 ± 0.00 0.08 ± 0.27 0.04 ± 0.19
14 0.00 ± 0.00 0.08 ± 0.27 0.00 ± 0.00
21 0.00 ± 0.00 0.08 ± 0.27 0.00 ± 0.00
28 0.00 ± 0.00 0.04 ± 0.20 0.00 ± 0.00
Mean diff (Baseline –Day 7)
(P value) -0.04 ± 0.20
(0.317) NS 0.00 ± 0.00
(1.00) NS -0.04 ± 0.19
(0.284) NS
topical formulation of the present disclosure Vs All groups - 0.313 (NS) 1.000 (NS)
Krack Cream group Vs All - - 0.279
Mean diff (Baseline –Day 14)
(P value) -0.04 ± 0.20
(0.317) NS 0.00 ± 0.00
(1.00) NS -0.07 ± 0.27
(0.190) NS
topical formulation of the present disclosure Vs All groups - 0.313 (NS) 0.647 (NS)
Krack Cream group Vs All - - 0.184 (NS)
Mean diff (Baseline –Day 21)
(P value) -0.04 ± 0.20
(0.317) NS 0.00 ± 0.00
(1.00) NS -0.07 ± 0.27
(0.190) NS
topical formulation of the present disclosure Vs All groups - 0.313 (NS) 0.647 (NS)
Krack Cream group Vs All groups - - 0.184 (NS)
Mean diff (Baseline –Day 28)
(P value) -0.04 ± 0.20
(0.317) NS -0.04 ± 0.20
(0.317) NS -0.07 ± 0.27
(0.190) NS
topical formulation of the present disclosure Vs All groups - 1.000 (NS) 0.647 (NS)
Krack Cream group Vs All - - 0.647 (NS)
By Wilcoxon Sign Rank Test NS = Not Significant
By Mann Whitney U Test
4. Comparison of changes in mean overall clinical cutaneous score between the groups:
At baseline visit, the mean overall clinical cutaneous score was 7.00 in topical formulation of the present disclosure, 7.31 in commercially available product (Krack Cream) group and 7.19 in Amarantha wound healing cream group, and difference between the groups was not significant.
On day 7, the mean overall clinical cutaneous score showed a significant fall of 42.9% in topical formulation of the present disclosure, 21.6% among commercially available product (Krack Cream) group and 13.4% in Amarantha wound healing cream group from baseline visit. If compared change was significantly more in topical formulation of the present disclosure as compared to other two groups. If compared change was more in commercially available product (Krack Cream) group than Amarantha wound healing cream group, but difference was not significant. The same trend was observed on day 14 and day 21.
On day 28, the mean overall clinical cutaneous score showed a significant fall of 99.4% in topical formulation of the present disclosure, 72.6% among commercially available product (Krack Cream) group and 62.3% in Amarantha wound healing cream group from baseline visit. Change was more in topical formulation of the present disclosure as compared to the commercially available product (Krack Cream) group but difference was not significant. Change was significantly more in topical formulation of the present disclosure than Amarantha wound healing cream group. Further, change was more in the commercially available product (Krack Cream) group than Amarantha wound healing cream group, but difference was not significant.
Duration
(Days)
Mean Overall Clinical Cutaneous Score ( ? SD)

topical formulation of the present disclosure, (N = 26) Krack Cream (N = 26) Amarantha Wound Healing Cream group, (N = 27)
Baseline 7.00 ± 0.94 7.31 ± 0.88 7.19 ± 0.96
7 4.00 ± 2.00 5.73 ± 1.25 6.22 ± 1.19
14 1.73 ± 2.09 4.23 ± 2.47 5.11 ± 1.28
21 0.31 ± 0.84 2.65 ± 2.45 3.59 ± 2.37
28 0.04 ± 0.20 2.00 ± 2.45 2.70 ± 2.60
Mean diff (Baseline –Day 7)
(P value) *-3.00 ± 1.72
(0.001) *-1.58 ± 1.14
(0.001) *-0.96 ± 1.32
(0.002)
topical formulation of the present disclosure Vs All groups - *0.002 *0.001
Krack Cream group Vs All groups - - 0.06 (NS)
Mean diff (Baseline –Day 14)
(P value) *-5.27 ± 2.05
(0.001) *-3.08 ± 2.42
(0.001) *-2.07 ± 1.66
(0.001)
topical formulation of the present disclosure Vs All groups - *0.002 *0.001
Krack Cream Vs All group - - 0.153 (NS)
Mean diff (Baseline –Day 21)
(P value) *-6.69 ± 1.01
(0.001) *-4.65 ± 2.59
(0.001) *-3.59 ± 2.69
(0.001)
topical formulation of the present disclosure Vs All groups - *0.009 *0.001
commercially available product (Krack Cream)Vs All groups - - 0.124 (NS)
Mean diff (Baseline –Day 28)
(P value) *-6.96 ± 0.92
(0.001) *-5.31 ± 2.69
(0.001) *-4.48 ± 2.99
(0.001)
topical formulation of the present disclosure Vs All groups - 0.095 (NS) *0.009
Krack Cream Vs All group - - 0.992 (NS)
By Wilcoxon Sign Rank Test *Significant NS = Not Significant
By Mann Whitney U Test

5. Comparison of global assessment for overall change by physician between the groups:

When compared between groups, topical formulation of the present disclosure cream showed statistically significant overall change in cracked heel condition than other two groups.
Assessment Day 28
topical formulation of the present disclosure, (N = 26) Krack Cream (N = 26) Amarantha Wound Healing Cream group, (N = 27)
No. of Cases % No. of Cases % No. of Cases %
Not Assessed - - - - - -
Very Much Improved *25 96.2 11 42.3 07 25.9
Much Improved *01 03.8 06 23.1 06 22.2
Minimally Improved - - 08 30.8 10 37.0
No Change - - 01 03.8 04 14.8
Minimally Worse - - - - - -
Much Worse - - - - - -
Very Much Worse - - - - - -
By Chi - Square Test *P = 0.001 Significant

6. Comparison of global assessment for tolerability of study drugs assessed by physician and subjects between the groups:
As per global assessment for overall tolerability of study drugs assessed by physician and subjects at the end of the study, it was observed that 22 subjects (84.6%) reported excellent tolerability and 04 subjects (15.4%) reported good tolerability to topical formulation of the present disclosure. 19 subjects (73.1%) reported excellent tolerability and 07 subjects (26.9%) reported good tolerability to the commercially available product. 22 subjects (81.5%) reported excellent tolerability and 05 subjects (18.5%) reported good tolerability to Amarantha wound healing cream.

Tolerability Day 28
topical formulation of the present disclosure, (N = 26) Krack Cream group (N = 26) Amarantha Wound Healing Cream group, (N = 27)
No. of Cases % No. of Cases % No. of Cases %
Excellent 22 84.6 19 73.1 22 81.5
Good 04 15.4 07 26.9 05 18.5
Fair - - - - - -
Poor - - - - - -

7. Safety:
There were 4 (15.4%) adverse events in topical formulation of the present disclosure, 07 (26.9%) in the commercially available product (Krack Cream) group and 4 (14.8%) in Amarantha wound healing cream group reported during the study period. All these adverse events were mild in nature and subsided with treatment and did not require stoppage of the study drug application. As per investigator, these adverse events were unrelated to the study drugs.

Conclusion:
It can be concluded from the results of present clinical study that topical formulation of the present disclosure is safe to use in subjects suffering from cracked heels. The topical formulation of the present disclosure is significantly better effective in early healing of cracked heels, alleviating skin roughness, hyperkeratosis of skin and making skin soft than the commercially available product- Krack Cream and Amarantha wound healing cream. Thus, the topical formulation of the present disclosure is safe and effective treatment option for cracked heels.
TECHNICAL ADVANCEMENTS & ECONOMIC SIGINIFICANCE
The present disclosure described herein above has several technical advantages including, but not limited to, the realization of a topical formulation that:
? provides quick recovery from heel fissures within 15 days;
? is easy to prepare and cost effective; and
? has no side effects.
Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the disclosure to achieve one or more of the desired objects or results.
Any discussion of documents, acts, materials, devices, articles or the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application.
The numerical values mentioned for the various physical parameters, dimensions or quantities are only approximations and it is envisaged that the values higher/lower than the numerical values assigned to the parameters, dimensions or quantities fall within the scope of the disclosure, unless there is a statement in the specification specific to the contrary.
While considerable emphasis has been placed herein on the components and component parts of the preferred embodiments, it will be appreciated that many embodiments can be made and that many changes can be made in the preferred embodiments without departing from the principles of the disclosure. These and other changes in the preferred embodiment as well as other embodiments of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation.
,CLAIMS:WE CLAIM:
1. A topical formulation for alleviating heel fissures comprising:
i. extract of Madhuca indica in an amount in the range of 3 % to 15% by weight of the total mass of the formulation;
ii. exudate of Shorea robusta in an amount in the range of 5 % to 10 % by weight of the total mass of the formulation;
iii. extract of Mentha arvensis in an amount in the range of 0.4 % to 0.7 % by weight of the total mass of the formulation;
iv. Jatyadi Taila in an amount in the range of 3 % to 5% by weight of the total mass of the formulation;
v. Tankan Bhasma powder in an amount in the range of 0.7 % to 2.0 % by weight of the total mass of the formulation;
vi. at least one excipient in an amount in the range of 15% to 25% by weight of the total mass of the formulation; and
vii. a fluid medium in an amount in the range 55 % to 65 % by weight of the total mass of the formulation.
2. The topical formulation as claimed in claim 1, wherein said extract of Madhuca indica is oil extract derived from seeds of Madhuca indica.
3. The topical formulation as claimed in claim 1, wherein said exudate of Shorea robusta is derived from stem of Shorea robusta.
4. The topical formulation as claimed in claim 1, wherein said extract of Mentha arvensis is menthol crystals.
5. The topical formulation as claimed in claim 5, wherein said fluid medium is water.
6. The topical formulation as claimed in claim 1, wherein said excipient comprises:
a. a humectant in an amount in the range of 4.5 % to 10 % by weight of the total mass of the formulation;
b. a first preservative in an amount in the range of 0.1 % to 0.30 % by weight of the total mass of the formulation;
c. a second preservative in an amount in the range of 0.01% to 0.03% by weight of the total mass of the formulation;
d. a first emulsifier in an amount in the range of 4 % to 10 % by weight of the total mass of the formulation;
e. a second emulsifier in an amount in the range of 8 % to 10 % by weight of the total mass of the formulation;
f. a stabilizer in an amount in the range of 0.1 % to 0.3 % by weight of the total mass of the formulation;
g. an emollient in an amount in the range of 4 % to 6 % by weight of the total mass of the formulation; and
h. a fragrance in an amount in the range of 0.2 % to 0.5 % by weight of the total mass of the formulation.
7. The topical formulation as claimed in claim 6, wherein said humectant is selected from the group consisting of propylene glycol, glycerine, alpha hydroxyl acids, glyceryl triacetate, honey and water.
8. The topical formulation as claimed in claim 6, wherein said first preservative is methyl paraben sodium.
9. The topical formulation as claimed in claim 6, wherein said second preservative is propyl paraben sodium.
10. The topical formulation as claimed in claim 6, wherein said first emulsifier is selected from the group consisting of cetostearyl alcohol, glyceryl monostearate, polyglyceryl isostearate, hexyl laurate, and dimethicone.
11. The topical formulation as claimed in claim 6, wherein said second emulsifier is stearic acid
12. The topical formulation as claimed in claim 6, wherein said stabilizer is selected from the group consisting of butylated hydroxytoluene (BHT), disodium edetate, propyl gallate, butylated hydroxyanisole, citric acid, ascorbic acid, and sodium ascorbate.
13. The topical formulation as claimed in claim 6, wherein said emollient is selected from the group consisting of dimethicone, petrolatum, lanolin, and mineral oil.
14. The topical formulation as claimed in claim 1, wherein said formulation is in a dosage form selected from the group consisting of cream, gel, and ointment.
15. A process for the preparation of a topical formulation, the process comprising the following steps:
a. preparing an aqueous phase by
• heating water to a predetermined temperature, followed by adding Tankan Bhasma, a humectant, a first preservative, and a second preservative under stirring to the aqueous phase in the form of a solution,
b. separately preparing a first oil phase by
• mixing Madhuk oil and Jatyadi oil followed by heating to a temperature in the range of 60 °C to 90°C to obtain an oil mixture; and
• adding exudate of Shorea robusta to said oil mixture followed by adding a first emulsifier and a second emulsifier and heating at a temperature in the range of 60 °C to 90°C to obtain the first oil phase,
c. separately preparing a second oil phase by
• mixing Madhuk oil, Jatyadi oil, Mentha arvensis, stabilizer/antioxidant under stirring to obtain the second oil phase,

d. mixing said aqueous phase with the first oil phase followed by homogenization to obtain a first homogenous mixture;

e. mixing an emollient with said first homogenous mixture followed by adding the second oil phase under stirring to obtain a second homogenous mixture; and

f. adding fragrance to the second homogenous mixture to obtain the topical formulation.