FORM 2
THE PATENTS ACT 1970
(39 of 1970)
AND
The Patents Rules, 2003
PROVISIONAL SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
"TOPICAL STEROIDAL FORMULATION"

2. APPLICANT
(a) NAME: Lyka Labs Limited.
(b) NATIONALITY: Indian Company incorporated under the
Indian Companies Act, 1956
(c) ADDRESS: 101, Shivshakti Industrial Estate, Andheri-Kurla Road,
Andheri (East), Mumbai - 400059, Maharashtra, India.
3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention:

TECHNICAL FIELD OF THE INVENTION:
The present invention relates to topical formulation comprising corticosteroid along with antifungal drug, more specifically the present invention relates to topical formulation comprising Alclometasone Dipropionate with Miconazole Nitrate in the form of cream, ointment, gel or topical solution.
BACKGROUND AND PRIOR ART OF INVENTION:
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior. The adrenal glands are small, paired structures, one lying in front of each kidney. They produce three different types of steroids:
• Glucocorticosteroids such as Cortisol control carbohydrate, fat and protein metabolism and are anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanisms.
• Sex hormones are second steroid type produced by these adrenal glands is the sex steroids. Examples of these are the female hormones estrogen and progesterone and the male androgens such as testosterone. These same substances are also produced in much greater quantities by the ovaries in the female and the testicles in the male. The androgens are the group that is sometimes referred to as anabolic steroids.
• Mineralocorticoids such as aldosterone control electrolyte and water levels, mainly by promoting sodium retention in the kidney.
Topical glucocorticoids for dermal application were introduced more than 50 years ago and revolutionised the treatment of inflammatory skin diseases. Today these drugs are frequently administered, although systemic and local adverse drug reactions, especially skin atrophy, are feared complications of theiruse.

Alclometasone is synthetic glucocorticoid steroid for topical use in dermatology as anti¬inflammatory, antipruritic, antiallergic, antiproliferative and vasoconstrictive agent.
The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.
Alclometasone cream and ointment are indicated for the relief of corticosteroid-responsive dermatoses, including:
• atopic dermatitis
• eczema
• psoriasis
• allergic dermatitis
• contact dermatitis
• actinic dermatitis
• kiss-type allergy
• skin itch
Alclometasone may be used on sensitive skin sites (face, skinfolds); in pediatric patients 1 year or older and in geriatric patients.
Alclometasone dipropionate is chemically known as (7a-chloro-l lp, 17, 21-trihydroxy-16a-methylpregna-l, 4-diene-3, 20-dione 17, 21-dipropionate) having the following structural formula


Imidazole compounds make up an important class of antifungal compounds used to treat yeast and fungal infections.
Miconazole is an imidazole antifungal agent, developed by Janssen Pharmaceutica, and commonly applied topically (to the skin) or mucus membranes to cure fungal infections. It works by inhibiting the synthesis of ergosterol, a critical component of fungal cell membranes. It can also be used against certain species of Leishmania protozoa (which are a type of unicellular parasite), as these also contain ergosterol in their cell membranes. In addition to its antifungal and antiparasitic actions, it also has some limited antibacterial properties. Miconazole nitrate is 1- (2, 4-Dichloro-beta-[(2, 4-dichlorobenzyl) oxy] phenyl) imidazole nitrate. Miconazole has following structural formula.

Miconazole is mainly used externally for the treatment of Athlete's foot, Ringworm and Jock Itch. Internal application is used for oral or vaginal thrush (yeast infection). In addition the oral gel may also be used for the lip disorder angular cheilitis.

US 2004/0202706 disclosed methods for administering a dermatological agent to a subject are provided. In the subject methods an effective amount of a topical formulation of the dermatological agent is topically applied to a host. The topically applied formulation of dermatological agent is then occluded with a hydrogel patch, where a feature of the hydrogel patch is that it lacks a pharmaceutically active agent. Also provided are methods of treating a subject for a disease condition by administering a dermatological agent to the subject. Also provided are kits for use in practicing the subject methods, were dermatological agent claimed in the invention is steroid administering to a subject and in another claim dermatological is non-steroid along with hydrogel patch composition, this invention do not disclosed combination of steroid and anti-fungal administering to a subject.
US 2007/0196323, teaches a formulation for dermal delivery of a drug comprising a) drug; b) polyvinyl alcohol; and c) a solvent vehicle, wherein drug includes at least one member selected from the group consisting miconazole, oxiconazole, amorolfine, butenafine, naftifine, hydrocortisone valerate, alclometasone dipropionate, flumethasone pivolate, etc. It does not teach the combination of Alclometasone Dipropionate and Miconazole Nitrate in topical formulation.
US 7074392 disclosed about topical sustained release delivery system for delivery of antifungal agents to the finger or toenails achieving high penetration through the nails by combining the antifingal agent with a keratolytic agent and a humectant. The pharmaceutical sustained release topical preparation is provided in a varnish or spray form for treating the nail and surrounding tissues, where the active ingredient is an antifungal agent, a keratolytic agent, or preferably a combination of an antifungal and a keratolytic agent. The composition may further comprise an antibacterial, an antiviral, an antipsoriatic agents, or combinations thereof. However, said invention describe about delivery system for delivery of active ingredients to the finger or toenails rather than topical formulation comprising alclometasone Dipropionate and Miconazole Nitrate.
US 6656928 A composition for topical administration consisting essentially of (a) a corticosteroid, (b) a broad spectrum anti-fungal agent that treats both dermatophytes and

yeast, and (c) a drying agent. Such combination is useful to treat both dermatophytes and yeast. Anti-fungal agent is an imidazole anti-fungal such as clotrimazole is used. This invention not teaches about formulation ih cream or topical solution comprising Alclometasone Dipropionate and Miconazole Nitrate.
WO/2004/058262 relates to topical compositions of an antibacterial benzoquinolizine-2-carboxylic acid, incorporated either as the single therapeutic ingredient, or as an ingredient in novel combination with at least one agent selected from a retinoid, an antifungal agent, another antibacterial compound and/or a steroid/non-steroid anti¬inflammatory agent. It also describe a processes for preparation of the compositions, to use of the compositions in preparation of a medicament, and method of therapeutic or prophylactic use of such a composition for the treatment of dermal, ophthalmic, otic and nasal infections, with or without attendant inflammation.
US 5407663 is to provide a means of treating patients suffering from inflammatory conditions of the oral cavity using compositions containing both anti-inflammatory steroids and antifungal agents in liquid aqueous preparations that can be swished and expectorated as a mouthwash. Such therapy allows direct contact of the medication with the diseased mucous membranes and contacts areas of the oral cavity that usually are not reached with application of creams, gels, or ointments.
None of the above prior arts deals/discloses topical formulation in the form of cream or topical non-aqueous solution comprising Alclometasone Dipropionate and Miconazole Nitrate in order to prevent secondary fungal infection during the use of corticosteroid as use of corticosteroid without anti-fungal drug not only delays therapeutic response but the immunosuppressive action of corticosteroid interferes in the body defense mechanism to manage fungal infection.
However, patients suffering from dermotophyte or Candida infection to begin with get sensitized to fungal invasion and have secondary eczematous reaction. They are diagnosed as suffering from infective eczema. In this situation use of Alclometasone Dipropionate with Moconazole Nitrate is necessary to control eczema and eradicate fungus.

OBJECT OF THE INVENTION:
The principal object of this present invention is to provide the topical formulation in the form of cream, ointment, gel or topical solution comprising topical corticosteroid, Alclometasone Dipropionate with broad-spectrum antifungal agent Miconazole Nitrate.
Another object of this invention is to prevent secondary fungal infection, which occurs during the use of corticosteroid without consisting of anti-fungal drug. Combination of Alcometasone Dipropionate and Miconazole Nitrate prevents said infection.
A further object of this invention is to provide Alclometasone Dipropionate with Miconazole Nitrate in order to control eczema and eradicate fungus, in a patients suffering from dermatophyte or Candida infection.
DETAILED DESCRIPTION OF THE INVENTION:
The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.
The present invention describes a topical corticosteroid along with antifungal drug in the form of cream, ointment, gel or topical solution comprising Alclometasone Dipropionate along with broad-spectrum antifungal agent Miconazole Nitrate.
Alclometasone is synthetic glucocorticoid steroid for topical use in dermatology as anti¬inflammatory, antipruritic, antiallergic, antiproliferative and vasoconstrictive agent.
A combination of Alclometasone Dipropionate with Miconazole Nitrate is a combination of topical corticosteroid with broad spectrum antifungal agent Miconazole Nitrate.
Miconazole Nitrate in combination with Alclometasone Dipropionate, is useful for patients suffering from Eczema, Psoriasis or dermatitis and management of secondary

fungal infection, which occurs due to repeated itching and scratching of the skin leads to damage of the epidermis, a natural protective barrier.
In one embodiment, this invention provides topical combination comprising Alciometasone Dipropionate 0.05% w/w and Miconazole Nitrate 2.0% w/w. 2% overages of Alciometasone Dipropionate and 2% overages of Miconazole nitrate may be added.
In second embodiment, the cream is prepared by mixing oil phase and water phase under continuous stirring at 60-70° C, followed by cooling at room temperature. Preservative is added separately either in oil or water phase or after emulsion formation takes place. Penetration enhancer, antioxidant and other ingredients are added in the emulsion for the formation of stable cream. Alciometasone Dipropionate and Miconazole Nitrate are added before cream formation or during cream formation taking place. If required, pH of the cream is adjusted in the range of 3.0 -5.0 .
According to another preferred embodiment, the ointment of Alciometasone dipropionate and Miconazole nitrate may be prepared using excipients selected from the group consisting of sorbitan sesquioleate, propylene glycol, white soft paraffin and white bees wax.
In yet another embodiment , the gel of Alciometasone dipropionate and Miconazole nitrate may be prepared using Carbopol 980, Disodium EDTA, Propylene Glycol, lsopropyl Alcohol, Triethanol amine and Purified water. Preservatives Methyl Paraben and Propyl Parben may be added.
In another embodiment topical solution is prepared by dissolving Alciometasone Dipropionate in Propylene Glycol (P.G.) and Miconazole Nitrate in Polyethylene Glycol(P.K.G.) 400 with the aid of heat. Antioxidant is dissolved separately in Propylene Glycol followed by mixing all the three solution and making up the volume with Propylene Glycol and Polyethylene Glycol 400.

The following ingredients can be used in different combinations to prepare cream / ointment / gel / Topical solution:

Emulsifiers Cetostearyl alcohol 2-8 %
Cetomacrogol 1000 0.5-4%
Microcrystalline wax 2-5%
Oil bases Light liquid paraffin 2-8%
Soft paraffin 2-8%
Ointment base White soft paraffin up to 100% Bees Wax 2-10%
Gelling agent Carbopol 980 0.5-2%
Surfactant Sorbitan sesquioleate 0.1 - 2%
Preservatives Methyl paraben 0.05-0.25% Propylparaben 0.01-0.1% Chlorocresol 0.05-0.15%
Antioxidants Butylated hydroxy anisole 0.005-0.02%) Butylated hydroxy toluene 0.005-0.02% a-Tocopherol 0.01-0.05%
Penetration enhancer and solubaliser Propylene glycol 6-24% Hexylene Glycol 6-24% Iso propyl alcohol 5-15%
Chelating agent Disodium EDTA 0.005-0.2%
Buffering agents Citric acid 0.01-0.1%
Disodium hydrogen phosphate 0.001 -0.1%
pH adjusting agent Triethanolamine q.s.
Vehicle for Topical solution Polyethylene Glycol 400 40-60% Propylene Glycol 40- 60%
Purified Water Q.S
fhe invention is further illustrated by following non-limiting examples.

EXAMPLES
Example 1 :
Composition for the Preparation of Cream may be as follows:

Ingredients Concentration % (w/w)
Active Ingredients Alclometasone ■ Dipropionate 0.05% w/w

Miconazole Nitrate 2.0% w/w
Rmulsifiers Cetostearyl alcohol 2-8%

Cetomacrogol 1000 0.5-4%

Microcrystalline wax 2-5%
Oil bases Light liquid paraffin 2-8%

White soft paraffin 2-8%
Preservatives Methyl paraben 0.05-0.25%
Propyl paraben 0.01-0.1%
Antioxidant Butylated Hydroxy toluene 0.005 - 0.02%
Penetration enhancer And solubaliser Propylene glycol 6-24%
Chelating agent Disodium EDTA 0.005-0.2%
Buffering agents Citric acid 0.01-0.1%

Disodium hydrogen phosphate 0.001-0.1%
Purified water - -
Example 2:
Composition for the Preparation of ointment may be as follows:

Ingredients Concentration % (w/w)
Active Ingredients Alclometasone Dipropionate 0.05% w/w
Miconazole nitrate 2.0% w/w
Surfactants Sorbitan Sesquioleate 0.1-2.0%
Solubilizer Propylene glycol 5-15%

Ointment base White soft paraffin 80-95%
White bees wax 2-10%
Example 3:
Composition for the Preparation of Gel may be as follows:

Ingredients Concentration % (w/w)
Active Ingredients Alclometasone Dipropionate 0.05% w/w

Miconazole nitrate 2.0% w/w
Gelling Agent Carbopol 980 0.5-2.0%
Solubilizer Propylene glycol Isopropyl Alcohol 5-30 % 5-15%
pH Adjusting agent Triethanolamine q.s.
Preservatives Methyl paraben 0.05-0.25%
Propyl paraben 0.01-0.1%
Chelating agent Disodium EDTA 0.005-0.2%)
Vehicle Purified Water ' q.s.
Example 4:
Composition for the preparation of topical solution may be as follows -

Ingredient Concentration % (w/v)
Active Alclometasone Dipropionate 0.05% w/w
Miconazole nitrate 2.0%) w/w
Antioxidant Butylated hydroxy toluene 0.005 - 0.02%
Co-solvent Propylene Glycol Polyethylene Glycol 400 40 - 60% 40 - 60%