FORM 2
THE PATENTS ACT 1970 (39 of 1970)
AND
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
"HALOMETASONE MICROEMULSION BASED CREAM FORMULATION"
2. APPLICANTS:
(a) NAME: LYKA LABS LIMITED
(b)NATIONALITY: Indian Company incorporated under the 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 and the manner in which it is to be performed:

FIELD OF THE INVENTION:
The present invention relates to topical formulation of corticosteroid for the treatment of inflammatory and pruritic manifestation of non-infected corticosteroid responsive dermatoses like eczema. More particularly, the present invention relates to topical formulation comprising microemulsion of Halometasone for the treatment of inflammatory and pruritic manifestation of non-infected corticosteroid responsive dermatoses like eczema and further it relates to the process for preparation of said formulation.
BACKGROUND OF THE INVENTION:
A microemulsion is a transparent or nearly transparent, quasi-homogeneous; thermodynamically stable mixture of two immiscible liquids stabilized by surfactant (or mixture of surfactants). Microemulsions are clear, stable, isotropic liquid mixtures of oil, water and surfactant, frequently in combination with a cosurfactant. These emulsions form spontaneously and typically consist of an aqueous phase, an organic phase, and a surfactant/co-surfactant component. Microemulsions are conceived to be an ideal vehicle for drug delivery since they provide a long shelf-life due to their thermodynamic nature and infinite physical stability.
Halometasone is a topical corticosteroid with glucocorticoid activity. It has antiinflammatory action with significant and tolerability profile. It exhibits immunosuppressive effects by inhibiting the release of various cytokines. Corticosteroid act by the induction of lipocortins which prevent the formation of prostaglandins and leukotrienes. Both prostaglandins and leukotrienes are mediators which lead to inflammation. Halometasone acts by blocking their production, thus acting as antiinflammatory agent.
Chemically, Halometasone monohydrate is (6a,lip,16a)-2-chloro-6,9-difluoro-ll, 17,21-trihydroxy-16-methylpregna-l,4-diene-3,20-dione monohydrate, It has the following structural formula-


WO2008096351 discloses a transdermal, transmucosal, microemulsion or a nano-sized emulsion suitable for substantially extra-vascular application of at least one biologically active substance to biological membranes of a mammal, comprising: (i) a pharmaceutical or cosmetic composition comprising: a. propylene carbonate; b. at least one oil or source of fatty acid or surfactant; arid c. water; in combination with (ii) the at least one biologically active substance: wherein the propylene carbonate is adapted to enhance the bioavailability of said at least one biologically active substance. The said microemulsion is for treatment of diabetics,
WO 2008070129 discloses a pharmaceutical formulation in oral dosage form comprising a glucocorticoid conjointly with, a lipoxin compound, or an oxylipin compound, or with a combination of aspirin and an omega-3 fatty acid for the treatment of inflammatory disease. The said publication further discloses liquid dosage forms include emulsions, microemulsions, solutions, suspensions, syrups and elixirs.
US Patent No. 4512987 discloses pharmaceutical preparations for topical administration, in the form of creams, ointments, foams, pastes or gels, which contain the anti-inflammatorily active glucocorticoid 2-chloro-6 alpha ,9 alpha -difluoro-16 alpha -methyl-11 beta ,17 alpha ,21-trihydroxy-pregna-l,4-diene-3,20-dione (2-chloroflumethasone, halometasone) and the antimicrobial agent 2,4,4'-trichloro-2'-hydroxy-diphenyl ether (triclosan).
Chinese Patent No. 10147418 discloses a single preparation and compound preparation using halometasone as main constituent. The pharmaceuticals can be made into jellies, supensoid agent, liquor and pulvis, and the like, which are administrated in a percutaneous way. The said patent does not discloses Halometasone microemulsion.

Indian Patent No. 209289 discloses a microemulsion of a pharmaceutical composition containing immunosuppressant agent such as tacrolimus.
The advantages of microemulsion over coarse emulsion include its ease of preparation due to spontaneous formation, high solubility of drug, small droplet size, thermodynamic stability, transparent and elegant appearance, increased drug loading, enhanced penetration through the biological membranes, increased bioavailability, long shelf-life and less inter- and intra-individual variability in drug pharmacokinetics. These advantages make microemulsions attractive drug delivery systems.
Hence in view of the above, the present inventors have come up with efficacious microemulsion based topical formulation for effective delivery of Halometasone monohydrate for the treatment of inflammatory and pruritic manifestation of non-infected corticosteroid responsive dermatoses like eczema.
Thus the object of the present invention is to develop a topical formulation comprising microemulsion of Halometasone monohydrate for the treatment of inflammatory and pruritic manifestation of non-infected corticosteroid responsive dermatoses like eczema.
SUMMARY OF THE INVENTION:
In accordance with the above objective, the present invention provides a stable microemulsion based topical formulation of Halometasone monohydrate for the treatment of inflammatory and pruritic manifestation of non-infected corticosteroid responsive dermatoses like eczema.
The present invention also provides the process for preparation of said topical formulation.

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 term "topical" as employed herein relates to the use of the active ingredient
incorporated in a suitable pharmaceutical carrier, and applied at the site of the disease for
exertion of local action.
In a preferred embodiment, the present invention provides a stable topical formulation comprising microemulsion of Halometasone monohydrate along with pharmaceutically accepted excipients, for the treatment of inflammatory and pruritic manifestation of non-infected corticosteroid responsive dermatoses like eczema.
In another embodiment, the present invention provides topical formulation comprising microemulsion of Halometasone monohydrate in the form of cream.
In another embodiment, the present invention provides topical formulation comprising microemulsion of Halometasone monohydrate, wherein said Halometasone monohydrate is present in an amount ranges from 0.025-0.05%.
In another embodiment of the present invention, the pharmaceutical excipients are selected from the group comprising of emollients, oleaginous vehicles, emulsifying agents, oil bases, preservatives, surfactants, penetration enhancers, solubilizers and combinations thereof.
In another embodiment, the present invention provides a stable microemulsion based topical cream formulation comprising Halometasone monohydrate in the range of 0.025-0.05%, an emollient, an oleaginous vehicle, an emulsifying agent and an oil base as microemulsion forming components alongwith other pharmaceutically acceptable excipients.

According to the embodiment of the present invention, the topical cream of Halometasone monohydrate is prepared by using pharmaceutical excipients selected from the group consisting of Isopropyl palmitate, Cetostearyl alcohol, Cetomacrogol 1000, White soft paraffin, Chlorocresol, Germaben HE, Transcutol - P, Polysorbate 80, Propylene glycol, Butanol and Isopropyl myristate.
In another preferred embodiment, the present invention provides a process for manufacturing the formulation of invention, comprises following steps:-
Part I:
1. Mixing isopropyl myristate, polysorbate 80, butanol and transcutol P on magnetic stirrer;
2. dissolving Halometasone monohydrate in some amount of propylene glycol with aid of heat;
3. mixing solutions of step (2) with step (!) under stirring; and
4. mixing purified water with solution of step (3) under stirring.
Part II:
1. Melting cetostearyl alcohol, cetomacrogol 1000, isopropyl myristate, isopropyl palmitate and white soft paraffin in a S. S vessel;
2. heating water to 60°C - 70°C and mixing it with step 1 under stirring;
3. dissolving Chlorocresol in propylene glycol and mixing with solution of step 2 under stirring;
4. adding germaben HE to step 3 at temperature below 40°C.
Part III:
mixing of 10 parts of Part I with 90 parts of Part II of cream base under stirring and allowing the microemulsion based cream to stand for 24 hrs before filling.
The instant invention is more specifically explained by following examples. However, it should be understood that the scope of the present invention is not limited by the examples in any manner. It will be appreciated by any person skilled in this art that the

present invention includes following examples and further can be modified and altered within the technical scope of the present invention.
Examples: Example 1
Microemulsion based topical cream formulation:

Function Ingredients Concentration w/w
Active ingredient Halometasone monohydrate 0.025-0.05%
Emollient, oleaginous vehicle Isopropyl palmitate 0.05-5.0%
Emulsifying agent, Emollient Cetostearyl alcohol 2-10%

Cetomacrogol 1000 1-5%
Oil base White soft paraffin 2-15%
Preservative Chlorocresol 0.05-0.15%

Germaben HE 0.05-0.1%
Surfactant Transcutol - P 0.5-2%
Polysorbate 80 1-5%
Penetration enhancer, solubilizer Propylene glycol 2-25%

Butanol 0.5-2%
Isopropyl myristate 1-10%
Vehicle Purified water q.s.
Overages of Halometasone monohydrate can be added for the long term stability purpose.
Stability study of the product is carried out as per 1CH guidelines for 6 months under accelerated condition of 40°C / 75% RH and real time condition of 30°C / 65%RH and the product is found to be stable under aforesaid condition. Globule size of the microemulsion is less than 200 nm

We Claim,
1. A stable microemulsion based topical cream formulation comprising Halometasone monohydrate in the range of 0.025-0.05%, an emollient, an oleaginous vehicle, an emulsifying agent and an oil base as microemulsion forming components alongwith other pharmaceutically acceptable excipients.
2. The stable microemulsion based topical cream formulation according to claim 1, wherein the emollient /oleaginous vehicle is isopropyl palmitate in the range of 0.05-5.0%.
3. The stable microemulsion based topical formulation according to claim 1, wherein emulsifying agent is selected from cetostearyl alcohol in the range of 2-10% or cetomacrogol 1000 in the range of 1 -5% or combination thereof.
4. The stable microemulsion based topical formulation according to claim 1, wherein the oil base is white soft paraffin in the range of 2-15%.
5. The stable microemulsion based topical formulation according to claim 1, wherein the pharmaceutically acceptable excipients are selected from the group comprising of preservatives, surfactants, penetration enhancers, solubilizers and combinations thereof.
6. The stable microemulsion based topical formulation according to claim 1 and 5, wherein the preservative is selected from chlorocresol in the range of 0.05-0.15% or germaben HE in the range of 0.05-0.1% or combination thereof.
7. The stable microemulsion based topical formulation according to claim 1 and 5, wherein the surfactant is selected from transcutol - P in the range of 0.5-2.0% or polysorbate 80 in the range of 1-5% or combination thereof.

8. The stable microemulsion based topical formulation according to claim 1 and 5, wherein the solubiliser/ penetration enhancer is selected from propylene glycol in the range of 2-25% or Butanol in the range of 0.5-2% or isopropyl myristate in the range of 1-10% or combinations thereof.
9. A process for manufacture of the formulation according to claim 1-8 comprising

a) mixing isopropyl myristate, polysorbate 80, butanol and transcutol P on magnetic stirrer;
b) dissolving Halometasone monohydrate in 2-25% of propylene glycol with aid of heat;
c) mixing solutions of step (b) with step (a) under stirring;
d) mixing purified water with solution of step (c) under stirring;
e) melting cetostearyl alcohol, cetomacrogol 1000, isopropyl myristate, isopropyl palmitate and white soft paraffin in a S. S vessel;
f) heating water to 60°C - 70°C and mixing it with step (e) under stirring;
g) dissolving Chlorocresol in propylene glycol and mixing with solution of step (f) under stirring;
h) adding germaben 1IE to step (g) at temperature below 40°C; i) mixing of 10 parts of step (d) with 90 parts of step (h) under stirring; and j) allowing the microemulsion based cream of step (i) to stand for 24 hrs before filling.