Claims:1. A foot crack healing formulation comprises of
i) cetrimide,
ii) dichlorophen;
iii) menthol; and
iv) pharmaceutically acceptable excipient.
2. The formulation as claimed in claim 1 wherein the amount of cetrimide is 0.3-0.5% by weight.
3. The formulation as claimed in claim 1, wherein the amount of dichlophen is 0.15-0.25%.
4. The formulation as claimed in claim 1, wherein the amount of menthol is 0.05-0.1% by weight.
5. The formulation as claimed in claim 1, wherein the pharmaceutical acceptable excipient is selected from a group consisting of hydrocarbon base, emulsifying agent, preservative, rheological modifier, water or the combination thereof.
6. The formulation as claimed in claim 5, wherein the hydrocarbon base is white petroleum jelly.
7. The formulation as claimed in claim 5, wherein the emulsifying agent is polyoxyethylenesorbitan monooleate.
8. The formulation as claimed in claim 5, wherein the preservative is methyl paraben.
9. The formulation as claimed in claim 1 is cream.
10. The formulation as claimed in claim 9, wherein the cream is water-in-oil based cream.
11. The formulation as claimed in claim 1, wherein pH of the formulation is 6.0-6.5.
12. A process for preparing foot crack healing formulation comprising the steps of
i) preparing an oil phase by melting a hydrocarbon base at 75°C first and dichlorophen and menthol are added into the said base;
ii) preparing an aqueous phase by adding cetrimide, an emulsifying agent and a preservative in water to obtain a mixture and the said mixture is subjected for heating at 75°C;
iii) adding step (ii) into step (i) at 75°C and stirring the product until the temperature has dropped to 40°C;
iv) adding a rheological modifier into the product as obtained in step (iii).
13. The formulation as claimed in claim 1 as and when applied for a foot crack of an adult, elder, children or diabetic person.
, Description:FORM-2
THE PATENTS ACT, 1970
(39 OF 1970)
&
THE PATENT RULES, 2003
COMPLETE SPECIFICATION
(SECTION 10, RULE 13)

TITLE
“A FOOT CRACK HEALING FORMULATION AND THE METHOD THEREOF”

APPLICANT(S)
DR. S. K. AGRAWAL and MRS. MADHAVI LATA AGRAWAL,
Both Indian Nationals,
Of Qtr. No. C-7, M. P. Nagar, Niharika Road,
Korba, Pin-495677, Chhattisgarh, India

The following specification particularly describes the nature of the invention and the manner in which it is to be performed

FIELD OF THE INVENTION
The present invention relates to foot crack healing. More particularly, the present invention relates to foot crack healing formulation comprising a combination of cetrimide, dicholorophen and menthol and method of preparing the formulation.

BACKGROUND ART

The feet are flexible structures of bones, joints, muscles, and soft tissues including heel part that let us stand upright and perform activities like walking, running, and jumping. The foot crack is different from callouses, corns, warts, eczema, wrinkles, the thinning of the skin which comes from age, dry skin, chaffed skin, chapped skin or any other skin condition.
Except the sole of your foot, sebaceous gland which is a small gland present in the skin that is responsible to secrete a lubricating oily matter (sebum) into the hair follicles to lubricate the skin and hair. So, your foot or feet is an excluded part of the body from the naturally occurring lubrication process. Moreover, over exposure to dirt and sun and certain medical condition such as diabetes, atopic dermatitis, psoriasis (more often palmoplantar psoriasis), juvenile planter dermatosis, plamoplantar keratoderma, hypothyroidism, excessive obesity, dry thickened skin, prolong standing on hard surfaces or floorings, open-back shoes with no support pad under the foot, prolong exposure of wet shocks are the causes for cracked feet. The symptoms are red & flaky patches, rough skin around the rim of the feet and on the feet, itchiness, and cracks on the underside of fissures or the feet, rashes accompanied by itching and bleeding from the cracks.
In diabetes, the neuropathy in association with abnormal loading of foot, repeated micro trauma and the metabolic abnormalities causing the cracked foot in more troublesome sometimes in severe condition (ulceration) where the surgery is an only option (S. C. Mishra et al, the bmj | BMJ 2017;359:Supp 1 & M.P. KHANOLKAR, Q J Med 2008; 101:685–695).
Currently, the topical therapy containing keratolytic agent or humectant/water-retaining agents such as salicylic acid, urea, saccharide isomerate, alpha-hydroxy acids are used as heel cracked healing agents.

The limitations of these products i) are restricted to heel area only; ii) are not found as a good therapy in diabetic foot cracked management; iii) can cause discomfort and stinging when applied to the broken skin & iv) are not easily washed off; & v) need over a month time to show the improvement in cracked heels (Ref: BPJ Issue 65, Cracked Heels, Stop them in their tracks, Pg No.: 39-40).
In existing technology, the heel cracked healing composition is disclosed by Pourbastani in US Patent document US20050232957 date of publication June 28, 2001 wherein the composition comprises 2-10% of salicylic acid and 0.25-1.0% of hydrocortisone (steroid). However, this prior art uses salicylic acid and the problems associated with salicylic acid is discussed as above. Also, this prior art uses the steroid in conjunction with salicylic acid. The side effects of topically applied hydrocortisone are skin redness/burning/itching/peeling, thinning of your skin, blistering skin, stretch marks, menstrual period changes, acne etc. The composition of US’957’ may be sensitive to the children. Further, use of US’957’ is restricted to heel area only and that too takes over a month time to show the improvement and takes several months’ to heal completely. US’957’ doesn’t address the effect in diabetic foot crack patient.
Few herbal cracked formulations are suggested in the existing art. One of the herbal cream for the treatment of cracked heel is addressed by VIRENDRA V. PATIL et al (Virendra V. Patil et al, formulation and evaluation of crack cream from plant extracts, Vol 12, Issue 3, 2020) in which the cream is prepared by combining Azadirachta indica (neem laves) along with two another plants and pharmaceutical excipients wherein the neem leaves was boiled. Azadirachtin, the principal constituent of neem for the therapeutic effect is heat sensitive substance [Gabriela Esparza-Díaz, Azadirachtin Extraction Using Cold Press and Soxhlet Methods, Biopestic. Int. 6(1): 45–51 (2010), Pg No. 45-51] and therefore either cold-pressing technique or maceration method is recommended for extracting the phytoconstituents from neem leaves. Also, Patil et al doesn’t suggest the real time effect of the herbal cream in human being covering the whole feet. In fact Patil et al is absolutely silent on the therapeutic effect of the cream including duration of the treatment. Further, Patil et al doesn’t suggest the effect in diabetic foot cracked patient. Since the pH of cream of Patil et al is above 7.0 the formulation may not be ideally compatible with the sole of human feet [as the skin surface pH is significantly higher on the sole (mean value 6.25) than on the dorsal surface (5.23)]. Though a phase separation study of the cream via thermal stability test is carried out in Patil et al but the prior art is failed to address the shelf-life of the formulation as to conclude the overall stability of the formulation.
Another herbal cracked feet gel is proposed by S. Gupta & R. Acharya [S. Gupta & R. Acharya, Management of Padadari (cracked feet) with Rakta Snuhi (Euphorbia caducifolia Haines. An International Quarterly Journal of Research in Ayurveda, July 12, 2019, IP: 157.32.133.233 based formulation: An open-labeled clinical study). The duration of the treatment of Gupta et al is 21 days and the follow up is after 7 days. Also, since the age as selected in this prior art is in between 18-70, the formulation may not be suitable to the children. Further, this prior art doesn’t suggest the effect of formulation in diabetic foot cracked patient. Also, Aerosil which herein is a thickener not a preservative. Since there are no preservatives and the formulation type is herbal, the system may not capable to prevent the microbial growth for the longer period. Further, this prior art is failed to address the shelf-life of the formulation as to conclude the overall stability of the formulation. And no product is commercially viable if the stability of such product is under question or the shelf life of the product is short.
In existing art, 0.5% cetrimide cream (VANTAGE) is used as a mild antiseptic to treat minor burn, minor scalds, minor wounds, cuts, grazes and minor abrasions (Drugs.com, Cetrimide Cream BP). However, in the existing art, cetrimide is not used to treat cracked feet.

In existing art, dichlorophen, an anthelmintic (worm treatment) which is used in the treatment of infection caused by tapeworms, dwarf tapeworm and pork tapeworm and is usually administered by mouth as tablets. Also used against animal ringworm, as a fungicide and as a germicide in soaps. A non-patent literature (MSDS, Dichlorophen, SC-255083) teaches that “Dicholophen is known to cause significant inflammation of the skin either following direct contact or after a delay of some time. Repeated exposure can cause contact dermatitis which is characterized by redness, swelling and blistering. Open cuts, abraded or irritated skin should not be exposed to this material. Entry into the blood-stream, through, for example, cuts, abrasions or lesions, may produce systemic injury with harmful effects.” U.S. Department of Health and Human Services (https://drugs.ncats.io/drug/T1J0JOU64O) teaches that “Dichlorophene is a halogenated phenolic compound that functions as a bacteriocide and fungicide in cosmetics. Dichlorophene was reported to be used in a total of five cosmetic formulations at concentrations of 0% to 1.0%. Dichlorophen is used in the treatment of tapeworm infestation in man and animals and is the basis of a preparation against athlete’s foot.”. However, this prior art uses the broad range of dichlorophen. Contrarily, it is found by the present inventors that all the ranges as suggested by this prior art is not at all useful in the treatment of cracked foot.

Mayon’s “Foot cracked heel repair cream” comprises menthol and eucalyptus oil or ESENTI® cracked heel cream comprises menthol, peppermint and vitamin E is available in the market. However, these products are useful to heel area only. Also, these products need several months to heal the cracked heel completely. Further, these products are not useful in diabetic cracked feet patient. Moreover, the major therapeutic constituent of mentha species is flavonoid which is a heat sensitive material. As the material is heat sensitive the same may not be stable in processing of the formulation without the improved combination of the excipient. Also, as the menthol is not freely aqueous soluble and no pre-clinical and clinical data as to understand the permeation effect of the drug, the overall therapeutic effect of the formulation is under question.
Therefore, there is a need to provide a foot crack healing formulation.

OBJECTIVE OF THE INVENTION
The primary object of the invention is to overcome the aforementioned drawbacks by the provision of a topical formulation for use in fast healing epidermal cracks on the sole of whole foot.

Another objective of the invention is to provide a safe and effective foot crack healing formulation for the diabetic patients.

Yet another objective of the invention is to provide a safe and effective foot crack healing formulation for the children.

Yet another objective of the invention is to provide a foot crack healing formulation which is compatible with the human foot skin.

Yet another objective of the invention is to provide a stable foot crack healing formulation.

Yet another objective of the invention is to provide a cost effective and easy to apply formulation for treating cracked feet.

Further objective of the invention is to provide a process for preparing the foot crack healing formulation.

SUMMARY OF THE INVENTION

According to one aspect, there is provided a foot crack healing formulation comprises of
i) cetrimide,
ii) dichlorophen;
iii) menthol; and
iv) pharmaceutical acceptable excipient.
According to another aspect of the invention, there is provided a process for preparing foot crack healing formulation comprising the steps of
i) preparing an oil phase by melting a hydrocarbon base at 75°C first and dichlorophen and menthol are added into the said base;
ii) preparing an aqueous phase by adding cetrimide, an emulsifying agent and a preservative in water to obtain a mixture and the said mixture is subjected for heating at 75°C;
iii) adding step (ii) into step (i) at 75°C and stirring the product until the temperature has dropped to 40°C;
iv) adding a rheological modifier into the product as obtained in step (iii).
In accordance with these and other objects, this will become apparent herein after, the instant invention will now be described with particular reference to the accompanying drawing.

BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS

Figure 1 schematically illustrates the whole foot in accordance with the present invention

Other objects, features and advantages of the inventions will be apparent from the following detailed description in conjunction with the accompanying drawings of the inventions.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a safe and effective topical formulation for use in fast healing epidermal cracks on the sole of whole foot (Fig. 1). The said formulation essentially includes an effective amount of
i) Cetrimide;
ii) Dicholorophen; and
iii) menthol
The said formulation also comprises pharmaceutical acceptable excipients selected from a group consisting of a base, emulsifying agent, preservative, rheological modifier and water.
A) CETRIMIDE:

Chemical name: Alkyltrimethylammonium bromide predominantly C14
Formula: C17H38BrN
Molecular weight: 336.39
Properties: Anti-septic, anti-bacterial, anti-fungal, anti-microbial, & surfactant
B) DICHLOROPHEN:

Chemical name: 2,2’-Methylenebis(4-chlorophenol)

Formula: C13H10Cl2O2

Molecular weight: 269.12

Properties: Veterinary fungicide, anthelmintic, anti-protozoan and anti-microbial

C) MENTHOL:

Chemical name: 2-Isopropyl-5-methylcyclohexanol

Formula: C10H20O

Molecular weight: 156.27

Properties: Anti-microbial, anti-cancer, anti-inflammatory, analgesic, aesthetic & cooling agent
In preferred embodiment of the invention, the amount of cetrimide is 0.3-0.5% by weight while the amount of dicholorophen and menthol is 0.15-0.25% and 0.05-0.1% by weight respectively.
In preferred embodiment of the invention, the base is a hydrocarbon base.
In preferred embodiment of the invention, the hydrocarbon base is white petroleum jelly.
In preferred embodiment of the invention, the emulsifying agent is Tween 80 (Polyoxyethylenesorbitan monooleate).
In preferred embodiment of the invention, the rheological modifier is cetostrearyl alcohol.
In preferred embodiment of the invention, the preservative is methyl paraben.
In preferred embodiment of the invention, the topical formulation is cream.
In preferred embodiment of the invention, the cream is water-in-oil (W/O) based cream.
In preferred embodiment of the invention, pH of the formulation is 6.0-6.5.
In an embodiment of the invention, the process for preparing foot crack healing formulation comprises of
i) preparing an oil phase by melting a hydrocarbon base at 75°C first and dichlorophen and menthol were are then added into the said base;
ii) preparing an aqueous phase by adding cetrimide, an emulsifying agent and a preservative in water to obtain a mixture and the said mixture is subjected for heating at 75°C;
iii) slowly adding step (ii) into step (i) at 75°C and stirring the product until the temperature has dropped to 40°C;
iv) adding a rheological modifier into the product as obtained in step (iii).
In an embodiment of the invention, the formulation would be useful to treat cracked foot of an adult, elder, children and diabetic persons. In another embodiment, the formulation would be useful to treat the Athlete’s foot.
The invention is now illustrated by the non-limiting examples:
Materials: The active cetrimide, dicholorophen and menthol were procured from Sigma Aldrich, Mumbai, India. White Petroleum Jelly, Tween 80 & cetostrearyl alcohol were purchased from Merck Limited, Mumbai, India. Milli-Q® IQ 7000 Type-1 water was also purchased from Merck.

EXAMPLE 1 (Inventive example)
Ingredients Quantity (% Wt)
Cetrimide 0.5%
Dichlorophen 0.20%
Menthol 0.09%
White petroleum jelly 24.74%
Tween 80 48.61%
Methyl Paraben 0.2%
Cetostearyl alcohol 0.92%
Water 24.74%

Method: The oil phase was prepared by melting white petroleum jelly (24.74%) at the 75°C first and dichlorophen (0.20%) and menthol (0.09%) were then added into it. The aqueous phase was separately prepared by adding the cetrimide, tween 80 and methyl paraben in water and the said mixture was subjected for heating at 75°C. The aqueous phase was slowly added into the oil phase with moderate stirring (manually) when the water and oil phase were at the same temperature (75°C) and the stirring was continued until the temperature has dropped from 75°C to 40°C to obtain a W/O emulsion type cream. Cetostrearyl alcohol (0.92%) was added to increase the viscosity of the product. The product was then cooled and stored at room temperature.
EXAMPLE 2 (Comparative example)
Ingredients Quantity (% Wt)
Cetrimide 0.5%
Dichlorophen 0.10%
Menthol 0.09%
White petroleum jelly 24.79%
Tween 80 48.61%
Methyl Paraben 0.2%
Cetostearyl alcohol 0.92%
Water 24.79%

Method: The cream was prepared as per the method described in Example 1 except the quantity of Dichlorophen.
EXAMPLE 3 (Comparative example)
Ingredients Quantity (% Wt)
Cetrimide 0.5%
Dichlorophen 0.30%
Menthol 0.09%
White petroleum jelly 24.69%
Tween 80 48.61%
Methyl Paraben 0.2%
Cetostearyl alcohol 0.92%
Water 24.69%

Method: The cream was prepared as per the method described in Example 1 except the quantity of Dichlorophen.
EXAMPLE 4 (Comparative example)
Ingredients Quantity (% Wt)
Cetrimide 0.5%
Dichlorophen 0.21%
White petroleum jelly 24.78%
Tween 80 48.61%
Methyl Paraben 0.2%
Cetostearyl alcohol 0.92%
Water 24.78%

Method: The cream was prepared as per the method described in Example 1 except the methanol.
EXAMPLE 5 (Reference example)
Ingredients Quantity (% Wt)
Cetrimide 0.5%
Cream base q.s

Method: The cream was prepared as per the preparation as described in CETRIMIDE CREAM BP.
EXAMPLE 6 (Comparative example):
Ingredients Quantity (% Wt)
Dichlorophen 0.20%
White petroleum jelly 25.07%
Tween 80 48.54%
Methyl Paraben 0.2%
Cetostearyl alcohol 0.92%
Water 25.07%

Method: The cream was prepared as per the method described in Example 1 except the cetrimide and menthol. The other changes were done to obviate the error in calculation.
1. ORGANOLEPTIC CHARACTERIZATION:
The developed cream was tested for physical appearance, color, texture, pH, tube extrudability and spreadability
a. pH:
pH of the cream was determined by using Digital pH meter (Equiptronics). One gram of aforesaid cream was added in 100 ml of distilled water and stored for two hours. The pH of the cream was determined at 27°C using digital pH meter.

b. Tube Extrudability:
It is usual empirical test to measure the force required to extrude the material from tube. More quantity extruded signifies better Extrudability. The aforesaid cream was filled in clean, lacquered aluminum collapsible tube with nozzle tube of 5mm opening and applies pressure on tube by the help of finger. Tube extrudability was then determined by measuring amount of the formulation extruded.
c. Spreadability:
Spreadability of the formulations was determined by measuring the spreading diameter of 1g of sample between two horizontal glass plates (10?cm × 20?cm) after one minute. The standard weight applied to the upper plate was 500?g.
S= M × L/ T
Where, S= Spreadability, M= weight in the pan (tied to upper slide), L= Length moved by the slide, T= Time (in sec).
d. Viscosity Measurement:
The viscosity of the formulation was measured using Malvern zeta sizer at room temperature (28°C).

Table 1: Evaluation of cream
Parameter Example 1 Example 2 Example 3 Example 4 Example 5 Example 6
Colour Off white Off white Off white Off white Off white Off white
Odour Pleasant Pleasant Pleasant Pleasant Pleasant Pleasant
Appearance Smooth Smooth Smooth Smooth Smooth Smooth
Spreadability
(gcm/sec) 32.1±0.87 31.12±0.23 32.0±0.36 30.3±0.58 31.32±0.46 31.05±0.52
Viscosity(cp)
26075±
0.45 26075±
0.78 27070±
0.09 27072±
0..98 25073±
0.96 25090±
0.48
Extrudability Good Good Good Good Good Good
pH
6.2±0.04 6.3±0.05 6.3±0.09 6.4±0.05 5.2±0.05 5.4±0.05

The colour of all the creams was found as white while the appearance was observed as smooth. The extrudability of all the formulas was found as good. With regard to the spreadability and viscosity, no significant difference was found. It was also observed that Example 5 and 6 are not meeting with the criteria of desired pH and therefore is not compatible with the foot skin.
HUMAN TRIALS:

Section of patients:

i) Normal patients aged between 4 and 70 years of either sex with sign and symptoms of dry, itchy skin, hardness around the rim and cracks or fissures on the outer edge of the heel; deep fissures, bleeding and painful; infected fissures, cause a great deal of pain and discomfort; and having chronic exposure to water, dust and dryness were included in the study;

ii) Type II diabetic patients (who takes oral hypoglycemic B.D.) aged between 40 and 70 years of either sex with sign and symptoms of dry, itchy skin, hardness around the rim and cracks or fissures on the outer edge of the heel; deep fissures, bleeding and painful and infected fissures were included in this study;

iii) The patient having the history of allergic or hypersensitive reaction was excluded from the trial.

Dose:
Two times daily (Morning 9 AM and night 9 PM) up to 7 days for the affected area of normal and diabetic patients. Single time daily (night 9PM) up to 7 days for the affected area of the children.

Trail 1:
5 female patients aged between 50-70 with moderate cracks (3-15), moderate pain in crack areas, some superficial cracks/fissures in the feet, mild roughness & dryness in the feet & intermittently feels itching sensation, were selected for this study. The cream 2 times (morning & night) daily up to 4 days first was applied to the affected part then they called for the follow up (for observing the improvement). The patients were requested to apply the cream for further 3 days. After 1 week, the patients were observed as follows:
Table 2
Parameter Exam. 1 Exam. 2
Exam. 3 Exam. 4 Exam. 5 Exam. 6
reducing cracks ++++ ++ ++++ + - +
reducing pain ++++ ++ ++++ + - +
Reducing superficial cracks & fissures in the feet ++++ + ++++ + - +
reducing Roughness and dryness in the feet ++++ + ++++ + - +
reducing Itching sensation ++++ ++ + + - +
++++: excellent; ++: moderate; +: poor & -: no effect

Trail 2:
5 female children aged between 4-14 with mild cracks (1-2), mild pain in crack areas, one/two superficial cracks/fissures in the feet, slight roughness & dryness in the feet & occasionally feels itching sensation, were selected for this study. The cream single time (night) daily up to 3 days first was applied to the affected part then they called for the follow up (for observing the improvement). The patients were requested to apply the cream for further 4 days. After 1 week, the patients were observed as follows:

Table 3
Parameter Exam. 1 Exam. 2
Exam. 3 Exam. 4 Exam. 5 Exam. 6
reducing cracks ++++ + ++ + - +
reducing pain ++++ + ++ + - +
Reducing superficial cracks & fissures in the feet ++++ + ++ + - +
reducing Roughness and dryness in the feet ++++ + ++ + - +
reducing Itching sensation ++++ + + + - +
++++: excellent; ++: moderate; +: poor & -: no effect

Trail 3:
5 female diabetic patient aged between 35-50 with severe cracks (16-25), severe pain in cracked areas and the patient is unable to walk in the sun due to painin crack areas, deep cracks/fissures in the feet, moderate roughness & dryness in the feet & often feels itching sensation, were selected for this study. The cream two times (morning & night) daily up to 7 days first was applied to the affected part then they called for the follow up (for observing the improvement). The patients were requested to apply the cream for further 7 days if any except the group of Example 5 & 6 as in these groups the patients complain with enhanced itching and severe itching sensation respectively. Those patients were requested to stop the treatment and were given livocetrizine tablet @5mg for 3-5 Days.

Table 4
Parameter Exam. 1
(14 days) Exam. 2
(14 days)
Exam. 3
(14 days) Exam. 4
(14 days) Exam. 5
(7days) Exam. 6
(7 days)
reducing cracks ++++ + ++ + - -
reducing pain ++++ + ++ + - -
Reducing superficial cracks & fissures in the feet ++++ + ++ + - -
reducing Roughness and dryness in the feet ++++ + ++ + - -
reducing Itching sensation ++++ + + + @ @@
++++: excellent; ++: moderate; +: poor & -: no effect; @: enhanced itching sensation; @@: severe itching sensation

Trail 4:
5 female diabetic patient aged between 65-70 with very severe cracks (more than 25), sleep is disturbed due to pain at cracked areas, deep cracks in the feet and sometimes bleeding, course roughness & severe dryness in the feet & always feels itching sensation, were selected for this study (Considering the fact of itching sensation of Example 5 and 6, the trial was conducted for Example 1-4 in this group). The cream two times (morning & night) daily up to 7-10 days first was applied to the affected part then they called for the follow up (for observing the improvement). The patients were requested to apply the cream for further 7 days if any. After this period, the patients were observed as follows:
Table 5
Parameter Exam. 1 Exam. 2
Exam. 3 Exam. 4
reducing cracks ++++ + + +
reducing pain ++++ + + +
Reducing superficial cracks & fissures in the feet ++++ + + +
reducing Roughness and dryness in the feet ++++ + + +
reducing Itching sensation ++++ + + +
++++: excellent; ++: moderate; +: poor & -: no effect

Referring to Table1-5, the cream as exemplified in Example 5 (cetrimide 0.5% alone) doesn’t show any effect in foot crack. Rather positive itching sensation was observed in the diabetic group (Table 4). The cream as exemplified in Example 6 (Dichlorophen 0.20% alone) not only shows poor effect in the foot crack but also shows severe itching sensation in diabetic group (Table 4). The patients treated with the cream as exemplified in Example 4 (i.e. without menthol) shows overall poor effect in foot crack (Table 1-5). The cream as exemplified in Example 3 shows the equivalent effect as Example 1 but was failed to reduce the itching sensation (Table 1) significantly in normal patients which might be due to the higher concentration of Dichlorophen. Example 3 shows the moderate foot crack effect in children (Table 3) and diabetic group (Table 4) but the cream was also failed to reduce the itching sensation significantly. Further, the overall effect of the cream of Example 3 was found poor in the aged diabetic group (Table 5). The patients treated with the cream as exemplified in Example 2 shows the moderate effect in view of reducing cracks, pains & itching sensation in normal patients but shows poor effect in reducing superficial cracks & fissures and roughness and dryness in the feet (Table 2). The overall effect of the cream of Example 2 was found poor in children, diabetic & aged diabetic group (Table 3-5). Surprisingly the cream as exemplified in Example 1 shows the excellent effect throughout the patients (Table 2-5) including children (Table 3) and aged diabetic group (Table 5) which might be because of the unique combination of cetrimide, dichlorophen and menthol. The unique combination of cetrimide, dichlorophen and menthol as exemplified in Example 1 also solves the existing irritation problem of dichlorophen.
Stability studies:
Stability study of the cream as exemplified in Example 1 was conducted at 40±2°/75±5% RH as per the ICH guidelines. The samples were placed at temperature 40±2°/75±5% RH in a stability chamber. At periodic intervals of 1, 2, 3 and 6 months, all the samples which were stored at 40±2°/75±5% RH were studied for pH, appearance and viscosity and the results are hereinbelow:

Parameter 40±2°/75±5% RH
0 Month 1 month 2 month 3 month 6 month
pH 6.2±0.04 6.3±0.03 6.4±0.04 6.3±0.05 6.4±0.04
Appearance smooth smooth smooth smooth smooth
Viscosity 26075±
0.45 26071±
0.45 26074±
0.45 26072±
0.45 26075±
0.45

In the present context, pH is main indicator of the stability study as if pH of the formulation is not within the limit (6.0-6.5) over extended period of time then the formulation is of no use. The formulation shows the suitable pH (6.0-6.5) over the extended period of time. Also, there was no significant change found for the formulation with regard to appearance and viscosity.

Although the foregoing description of the present invention has been shown and described with reference to particular embodiments and applications thereof, it has been present for purposes of illustration and description and is not intended to be exhaustive or to limit the invention to the particular embodiments and applications disclosed. It will be apparent to those having ordinary skill in the art that a number of changes, modifications, variations, or alterations to the invention as described herein may be made, none of which departs from the spirit or scope of the present invention. The particular embodiments and applications were chosen and described to provide the best illustration of the principles of the invention and its practical application thereby enable one of ordinary skill in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated. All such changes, modifications, variations, and alterations should therefore be seen as being within the scope of the present invention as determined by the appended claims when interpreted in accordance with the breadth to which they are fairly, legally, and equitably entitled.