FIELD OF INVENTION
The present invention pertains to topical pharmaceutical formulations. More specifically, it pertains to novel non-staining topical formulation of turmeric, or extract thereof such as curcumin, curcuminoids with high water soluble property, enabling easy washing and removal of the staining compounds.
BACKGROUND OF INVENTION
Turmeric is a rhizomatous herbaceous perennial plant of the ginger family, Zingiberaceae which is native to tropical south Asia. Turmeric is often called as Indian saffron, as it is widely used as an alternative to far more expensive saffron. It is used as a coloring agent and also as a food additive. In Ayurvedic medicine, turmeric is thought to have many medicinal properties and many in India use it as a readily available antiseptic for cuts, burns and bruises. It is also used as an antiinflammatory and a antibacterial agent.'
It is estimated that 2-5% of turmeric is curcumin. Curcumin is the principal Curcuminoid of turmeric. Curcuminoids are responsible for the yellow color of turmeric. The principal curcuminoids of turmeric includes curcumin (77%), Demethoxycurcumin (18%) and Bis-demethoxycurcumin (5%). Curcumin can exist in at least two tautomeric forms, Keto and enol. The enol form is more energetically stable in the solid form than in solution. The Curcuminoids are polyphenols and are responsible for the yellow color of Turmeric. The phytochemical is pharmacologically safe and the safety profile is well-documented and known in literature.
Curcumin (l,7-bis-[4-hydroxy-3-methoxyphenyl]-l,6-heptadiene-2,5-dione) is known for its antitumor, antioxidant, antiarthritic, antiamyloid and anti-inflammatory properties. It may be effective in treating malaria, prevention of cancer, and may interfere with the replication of HIV Virus. Curcumin acts as a free radical scavenger and antioxidant, inhibiting lipid peroxidation and oxidative DNA damage. Curcumin has emerged as the newest "nutraceutical" which has efficacy against colon cancer, cystic fibrosis (CGF) defects, tumorigenesis, metastasis and a variety of other diseases.2

Anti-inflammatory action: One of the best-known therapeutic effects of curcumin is its anti inflammatory effect. Its comprehensive range of anti-inflammatory properties would be highly beneficial not only in chronic inflammatory diseases and cancer, but also in age-related health problems where subclinical inflammation is believed to be to the root cause. Whereas the common anti-inflammatory drugs do not reduce inflammation, other than the symptomatic relief of pain, Curcumin is probably the only complete anti-inflammatory molecule simultaneously modulating all the agents and pathways involved in inflammation. The most successful of the anti-inflammatory drugs in current use, the corticosteroids, owe their antiinflammatory action to the simultaneous inhibition of the two important transcription factors involved in inflammation, namely, NF-KB and AP-1. Both are inhibited by Curcumin, too3.
Anti-oxidant effects: Curcumin is a powerful antioxidant, many times more potent than Vitamin E and Vitamin C. While common antioxidants have been shown to offer no clinical benefit (sometimes even harmful), Curcumin is an exception. While many reasons can be cited for these effects, the most important one is the unique combination of antioxidant and anti-inflammatory property .of this molecule. This unique combination has a lot of therapeutic potential because oxidative stress and inflammation are intimately related, one inducing the other, and both need to be tackled simultaneously to break this vicious circle. It is not just a coincidence that most chronic diseases have oxidative stress and inflammation as pathological factors. Curcumin acts as a free radical scavenger and antioxidant, inhibiting lipid peroxidation and oxidative DNA damage. '
Wound healing: For Wound healing, extensive in vitro and in vivo testing has shown that turmeric inhibits chemically-induced epidermal ornithine decarboxylase activity, epidermal DNA synthesis, and the promotion of skin tumors in mice.4 Further studies suggest that turmeric also reduces arachidonic acid-induced rat paw and mouse skin edema and markedly inhibits epidermal lipoxygenase and cyclooxygenase activity in vitro.5 In humans, ingestion of turmeric has demonstrated a bacteriostatic or bactericidal effect against organisms involved in cholecystitis and has been used to treat biliary infections6. Topical application of a turmeric paste for the treatment of scabies has also shown good results.7
Curcumin has been shown to be the first p300/CBP-specific cell permeable, non-toxic histone acetyltransferases (HAT) inhibitor, and thus control gene expression. Its high antioxidant power

and metal chelating properties further widen its range of activities. Thus, Curcumin is able to act
at multiple targets and at multiple levels, and offer substantial benefits in a number of diseased
conditions.
Curcumin is thus, truly an incredible molecule with multiple bioactivities. This is so because
curcumin is capable of modulating the activities of a whole range of signaling pathways important
in health and diseases. Curcumin has been shown to have a wide variety of clinical effects in a
number of research studies.
Limitations of use due to staining effect
Though shown to have immense potential, one of the major factors limiting widespread use of curcumin for topical applications, is its staining action on skin. Commercially available formulations with turmeric/curcumin contain the same at concentrations of 10-20% turmeric and 1-2% curcumin respectively. However these are staining formulations which stain skin and clothes. Till date, no commercial formulation of turmeric, or extract thereof such as curcumin, curcuminoids is available which has non staining action on skin and is water washable. The present formulation of curcumin offers the unique advantage of being water washable, an advantage which is not offered by any of the known prior art formulations of curcumin. This feature leads to the technical advantage that the formulation neither stains the skin nor the clothes
One example of a topical non staining formulation of curcumin is disclosed in U.S Patent, Pub No 0070048393 Al which describes a combination of curcumin with other natural ingredients which lead to a non staining action. The formulation is a combination of blueberries, citrus juice, and lemon juice with curcumin which is indicated to be applied on the skin which is all natural products, making commercial manufacture practically difficult. In contrast, the present invention does not contain any of the above claimed additional natural ingredients which greatly facilitate standardization and manufacturing operations.
Advantages of the present invention: The present invention offers a number of advantages not offered by any of the existing formulation of turmeric, or extract thereof such as curcumin, curcuminoids in the prior art.

1. Water washable: Formulation can easily be washed with water, irrespective of the form in which it is used e.g. gel, cream, ointment, jelly, topical suspension, paste etc. applied on the skin.
2. Non staining action: The significant advantage of the present invention is that curcumin in the formulation does not leave yellow stain on the skin being water washable.
3. Better absorption: Better absorption through the skin, as the drug (turmeric or its extract thereof) is present in a soluble form (rather than particulate form), the absorption from the topical formulation will be higher and hence pharmacological activity will be enhanced.
4. Easy patient compliance: Still another advantage is its easy compliance for patients of all age, it being a topical application.
5. Smoothing and cooling effect: It may be used in combination with additives which may have analgesic, anti-inflammatory, rubefacient, soothing and/or cooling effect
6. Humectants: it may be formulated making use of humectants to prevent dryness of the skin at the site of application.
7. Easier and simpler formulation process: The process of formulation is simple and can be scale up using the usual semisolid manufacturing technique. ,
8. Pharmaceutical and Cosmetic use: The formulation with turmeric, or extract thereof such as curcumin, curcuminoids alone or in combinations with other additives may be used topically as an anti-inflammatory, antioxidant, protective barrier, beautifying aid or for any other therapeutic purpose e.g. wound healing, burn healing, antiseptic purpose, treatment/ prevention of cancer, scabies, psoriasis etc.
9. Easy choice of different formulation forms: A wide variety of topical semisolid dosage form may be formulated from the above water soluble form of curcumin such as gel, cream, lotion, ointment, jelly, moisturizer, sunscreen cream, beautifying aid, topical paste, topical suspension or any topical disorder. This has been achieved in present invention by use of special ingredient which solubilizes the curcumin in water rendering non staining property for wide use in different semisolid dosage form as mentioned above.

OBJECTS OF THE INVENTION
It is an object of the present invention to disclose a topical formulation of turmeric or extract
thereof such as curcumin, curcuminoids which is water washable.
Yet another object is to disclose a novel topical formulation of turmeric or extract thereof
which does not leave any yellow stain on the skin.
One more object of the invention is to disclose a topical formulation of turmeric or extract
thereof which is not only water washable and non-staining but can easily and conveniently be
formulated into a semi solid dosage form for topical application e.g. gel, cream, ointment,
jelly, emulsion, paste or any other like form.
SUMMARY OF THE INVENTION
The present invention discloses a novel non staining topical formulation of turmeric, or extract thereof such as curcumin, curcuminoids. The same has been achieved by use of a novel combination of hydrophilic excipients which act as specific solubilizer (SS) and a specialized base solution (SBS) alongwith curcumin. The formulation which is in a liquid/ semi solid form is quite stable.
STATEMENT OF INVENTION (NOVELTY OF THE INVENTION)
A topical formulation comprising turmeric or extracts thereof such as curcumin or curcuminoids wherein the composition is non-staining and includes a specialized base solution (SBS) and a specialized solubilizer (SS) alongwith curcumin or curcuminoids in specific concentrations.
DETAILED DESCRIPTION OF THE INVENTION
The present invention discloses a novel topical formulation of turmeric, or extract thereof such as curcumin, curcuminoids having water washable and non-staining property. The same comprises turmeric, or extract thereof such as curcumin, curcuminoids as the active molecule along with specific solubilizer (SS) and a specialized base solution (SBS).
Characteristic yellow colour of curcumin results in staining of skin and is one of the major drawbacks which have restricted its use in topical formulations. This problem has been

overcome in the present invention in which the curcumin formulation shows excellent water washable property and thereby does not leave yellow stain on the skin. Further, the formulation prepared is proposed to have a better pharmacological activity owing to water solubility.
An attempt was made in the present invention to overcome the problem of staining caused by turmeric, or extract thereof such as curcumin, curcuminoids, in formulation by adopting various approaches. The main thrust of overcoming the staining was by adopting a novel approach in which the turmeric, or extract thereof such as curcumin, curcuminoids is added to a specialized base solution (SBS) followed by addition of specific solubilizer (SS). The unique combination of ingredients results in a novel water soluble solution for turmeric, or extract thereof such as curcumin, curcuminoids formulation which is then added to the topical formulation base which may be cream or gel or ointment or liquid preparation or cosmetic preparation or any other semi solid preparation thereof and the resulting formulation has curcumin in water washable form.
Various combinations of specific solubilizer and specialized base solution (SBS) were prepared to solubilize the turmeric, or extract thereof such as curcumin, curcuminoids and duly evaluated. Polyoxyl 40 hydrogenated castor oil as a specific solubilizer (SS) was found to be most effective in the combination with the developed specialized base solution (SBS). The specialized base solution (SBS) was prepared using a combination of Glycerol, Propylene Glycol and Poly ethylene glycol of various grades (400-6000). The resultant solution constituting specific solubilizer (SS) and specialized base solution (SBS) was capable of solubilizing the turmeric, or extract thereof such as curcumin, curcuminoid and was hydrophilic enough to give clear solution when dissolved in water or any other aqueous base.
The final process for making the stable topical formulation comprises addition of the above prepared solution into base of the topical formulation. The topical formulation may or may not contain lipophilic/hydrophilic ingredients such as oadecanoic acid derivative, carboxymethyl cellulose derivative, hydroxypropylcellulose derivative, poly acrylic acid derivative, non ionic surfactant such as Polyoxyethylene alkyl ethers, stabilizing and emulsifying agent, saturated hydrocarbons derivative cetosteryl alcohol, etc, to increase the skin penetration of curcumin;

menthol or camphor added as a skin permeability enhancer. The formulation may include rubefacient agents such as capsaicin, methyl salicylate and oleum lini and a suitable fragrance.
An illustrative composition of the formulation of turmeric, or extract thereof such as curcumin, curcuminoids is given in Table 1 below. While components of the Specialized Base Solution (SBS) and the Specific Solubilizer (SS) remain the same, their concentrations can easily be varied, depending upon the concentration of active ingredient e.g. if active ingredient is less, then obviously less concentrated SBS and SS would be required. However, the moment one wishes to go in for higher concentration formulations, concentration of the SBS and SS components has to be increased correspondingly. The same is illustrated by way of examples 1 and 2 in which two formulations with different concentration of active ingredients are disclosed viz. 1% and 10% respectively. Table 1 Compostion of non-staining water washable topical formulation
(Table Removed)

Method of making the formulation and details of the composition of the formulation are
illustrated by way of example. Examples are given for two formulations having different
concentrations of active ingredient viz. 1% and 10% respectively.
Example 1: Water Washable curcumin (1%) topical formulation.
Composition of the SBS and SS suitable for 1% topical formulations is given in Table 2 and
Table 3 respectively. The process for formulating the same is as follows:
Step 1: Add turmeric, or extract thereof such as curcumin, curcuminoids (1.0%) to a
specialized base solution (SBS) and stir for 20-30 minutes at medium speed at room
temperature.

Step 2: Add specific solubilizer (SS) to the composition of step 1 and again stir for 20-30
minutes at medium speed at room temperature till a distinct viscous solution with reddish
orange appearance is obtained.
Step 3: Topical formulation base may also be formed separately by simple cream preparation
process by taking hydrophilic/lipophilic base, emulsifiers, solubilizing agents, stabilizing
agents, viscosity enhancer etc well known in prior art.
Step 4: The solubilized curcumin may be added to the aqueous portion of the cream.
Step 5: Additionally Fragrances and perfumes or other topically active ingredients such as
rubefacient, analgesic, anti-inflammatory etc. may be added to the formulation.
Table 2: Specialized base solution (SBS) for formulation containing 1% active ingredient

(Table Removed)
Table 3: Specific solubilizer (SS) for formulation containing 1% active ingredient
(Table Removed)

Example 2: Water washable curcumin (10%) topical formulation:
Composition of the SBS and SS suitable for 10% topical formulation is given in Table 4 and Table 5 respectively. The process for formulating the same is as follows:
Table 4: Composition of the specialized base solution (SBS) for formulation containing 10% active ingredient

(Table Removed)

Table 5: Composition of specific solubilizer (SS) containing 10% active ingredient
(Table Removed)

In other embodiments, the concentration of turmeric, or extract thereof such as curcumin,
curcuminoids can be easily increased e.g. from initial 0.1 % upto 10%. Appropriate variations
in the concentration of the components of SBS and SS can easily be carried out by those
skilled in the art, once the components and ingredients responsible for the solubility effect, as
disclosed above are known.
The above detailed description discloses the method and composition of a water washable and
non-staining topical formulation of curcumin. The basic innovation lies in the following
(i) unique specialized base (SBS) to which turmeric, or extract thereof such as curcumin,
curcuminoids is first added and
(ii) Specific solubilizer (SS) which makes the curcumin water soluble.
Depending upon the concentration of turmeric or extract thereof such as curcumin or
curcuminoids, appropriate change in the composition of solubilizer can be made as illustrated
by way of Examples 1 and Example 2.
The formulation according to this method was duly prepared and its non-staining property
verified experimentally. Cloths of various categories were duly taken and the formulation in
form of cream duly applied. Thereafter, cloth was washed and examined visually for stains.
For control, a cream of exact composition but without SBS and SS was taken and applied in
similar manner and subject to identical method of washing and visual examination.
Additionally, the formulation of the present invention was also tested on human volunteers as
follows. 2 g of the cream containing upto 1% curcumin was applied on the dorsal surface of
the hand, allowed to remain for 30 minutes and washed with running water thereafter.
Results are summarized in Table 6 below:

Table 6: Evaluation of non-staining effect of novel formulation on cloth and human skin.
(Table Removed)

Once the concept of using a combination of specialized base and specific solubilizer as disclosed herein is understood, variations to the same using different concentration of turmeric, or extract thereof such as curcumin, curcuminoids can be easily carried out by one skilled in the art. Although the invention has been described with reference to specific embodiments, this description is not meant to be construed in a limiting sense. Various modifications of the disclosed embodiments, as well as alternate embodiments of the invention, will become apparent to persons skilled in the art upon reference to the description of the invention. It is therefore contemplated that such modifications can be made without departing from the spirit or scope of the present invention as defined.
References:
1. www.wikepedia.com-Turmeric.
2. Kurien et.al, volume -5, number 4,2007.
3. Haefner B, Drug discovery today 2002; 7:653-63
4. Conney A H et al., Adv. Enzyme Regul., 31:385-396, 1991; Huang M T et al.,Cancer Res., 48:5941-5945, 1988; Lu Y P et al., Carcinogenesis, 14:293-297, 1993; Azuine M A, Bhide S V, Nutr Cancer, 17:77-83, 1992.
5. Rao T S et al., Indian J. Med. Res., 75:574-578, 1982; Conney A H et al., Adv. Enzyme Regul., 31:385-396, 1991; Huang M T et al., Cancer Res., 48:5941-5945, 1988.

6. Ramprasad C et al., Ind. J. Phys. and Pharm., 1:136-143, 1957; Lutumski J et al., Planta Med., 26:9-19, 1974.
7. Charles V, Charles S X., Trop. Geogr. Med., 44:178-181, 1992.

We claim:
1. A topical formulation comprising turmeric or extracts thereof such as curcumin or
curcuminoids along with excipients wherein the formulation is non-staining and includes
a. a specialized base solution (SBS)
b. a specialized solubilizer (SS)
in specific concentrations.
2. The topical formulation of claim 1 wherein the concentration of turmeric or extracts thereof such as curcumin or curcuminoids in the formulation ranges between 0.1 to 10%.
3. The topical formulation of claim 1 wherein the specialized solubilizer (SS) is a polyoxyl hydrogenated castor oil derivative such as K-140.
4. The topical formulation of claim 1 wherein the concentration of the specialized solubilizer (SS) polyoxyl hydrogenated castor oil derivative in the formulation ranges between 0.1-80
%.
5. The topical formulation of claim 1 wherein the specialized base solution (SBS) comprises propylene glycol, polyethylene glycol and glycerol.
6. The pharmaceutical composition of claim 1 wherein the concentration of SBS in the formulation ranges from 10-100 %.
7. The topical formulation of claim 1 and claim 5 wherein the concentration of propylene glycol in SBS ranges from 10-100%.
8. The topical formulation of claim 1 and claim 5 wherein the concentration of polyethylene glycol in SBS ranges from 5-80%.
9. The topical formulation of claim 1 and claim 5 wherein the concentration of glycerol in SBS ranges from 5-80%.

10. A process for preparation of the topical formulation of claim 1 comprising the steps of:
a. Taking appropriate amount of turmeric or extracts thereof such as curcumin or
curcuminoids corresponding to required concentration in the formulation
b. Adding it to SBS and SS
c. Stirring at room temperature
d. Adding to pharmaceutical cream base with stirring
11. A non-staining topical formulation of turmeric or extracts thereof such as curcumin or
curcuminoids as substantially described herein with reference to the examples.