DESC:
FORM 2

THE PATENTS ACT 1970
(39 of 1970)
&
THE PATENTS RULE 2003

COMPLETE SPECIFICATION
(Section 10 and rule 13)

TOPICAL PHARMACEUTICAL COMPOSITION OF FLUOCINOLONE ACETONIDE

APPLICANT
GLENMARK PHARMACEUTICALS LTD
Glenmark House,
HDO – Corporate Bldg.,
Wing -A, B. D. Sawant Marg, Chakala,
Andheri (East), Mumbai, Maharashtra – 400099, India

THE FOLLOWING SPECIFICATION DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED
RELATED APPLICATION
This application claims the benefit of Indian Provisional Application no. 201721005718 filed on February 17, 2017; which is hereby incorporated by reference in its entirety.
FILED OF INVENTION:
The present invention relates to pharmaceutical composition comprising Fluocinolone acetonide. Particularly, the invention relates to an oil composition for topical administration comprising therapeutically effective amount of Fluocinolone acetonide, a process for preparing the stable pharmaceutical composition and method of treating otic inflammation or skin disorders.

BACKGROUND OF THE INVENTION
Otitis is a general term for inflammation or infection of the ear, in both humans and other animals. Otitis externa, external otitis, or "swimmer's ear" involves the outer ear and ear canal. Otitis media or middle ear infection involves the middle ear. In otitis media, the ear is infected or clogged with fluid behind the ear drum, in the normally air-filled middle-ear space. Otitis interna or labyrinthitis involves the inner ear. The inner ear includes sensory organs for balance and hearing. Over the past 20 years, there are different kinds of otic applications such as topical ointment, spray, and drops, among others, which may be applied as required.
Atopic dermatitis, also known as atopic eczema, is a type of inflammation of the skin (dermatitis). It results in itchy, red, swollen, and cracked skin. There is no known cure for atopic dermatitis, although treatments may reduce the severity and frequency of flares. Topical corticosteroids have proven themselves effective in managing this disease.
Psoriasis is also a skin disorder characterized by patches of abnormal skin. These skin patches are typically red, itchy, and scaly. They may vary in severity from small and localized to complete body coverage. There are five main types of psoriasis: plaque, guttate, inverse, pustular, and erythrodermic. Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery-white scaly skin. These areas are called plaques and are most commonly found on the elbows, knees, scalp, and back. Scalp psoriasis can pop up as a single patch or several, and can even affect the entire scalp. It can also spread to the forehead, the back of neck, or behind the ears. The common treatment is use of medicated shampoos, creams, gels, oils, ointments, and soaps. Over-the-counter products often contain one of two medications – salicylic acid and coal tar.
Fluocinolone acetonide is a corticosteroid primarily used in dermatology to reduce skin inflammation and relieve itching. It is a synthetic hydrocortisone derivative. The chemical name for fluocinolone acetonide is (1S,2S,4R,8S,9S,11S,12R,13S,19S)-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one. It has the following structure

(Fluocinolone acetonide)
Fluocinolone acetonide is available in US in various dosage forms including cream, ointment, solution, oil etc. Hill Dermaceuticals currently markets fluocinolone acetonide topical oil as DERMA-SMOOTHE/FS® and otic drops as DERMOTIC®
GB1013180 relates to steroid pharmaceutical composition with presence of citric acid. However solution, suspension or emulsion based dosage forms are disclosed.
GB 1080699 relates to Topical pharmaceutical compositions containing steroids
WO2014106126 relates to Scalp and/or hair treatment compositions comprising corticosteroid and at least one non-corticosteroid anti-itch or anti-inflammatory agent.
US20140348787 relates to methods and compositions for treating ear infections especially in gel dosage form.
US20150297588 relates to sterile otic formulations of antibacterial and antifungal agent for treating ear infection
There still exists a need for stable topical oil formulation of fluocinolone acetonide which can be used for multiple skin disorders such as atopic dermatitis, scalp psoriasis and otitis.

SUMMARY OF THE INVENTION
The present patent application relates to a stable topical pharmaceutical composition comprising therapeutically effective amount of Fluocoinolone acetonide and organic acid. Current invention is non-aqueous oil based topical composition.
In an embodiment, the present invention relates to a stable topical pharmaceutical composition comprising therapeutically effective amount of Fluocoinolone acetonide and organic acid wherein the formulation is oil based system.
In another embodiment, the present invention relates to a stable topical pharmaceutical composition comprising therapeutically effective amount of Fluocoinolone acetonide and organic acid wherein formulation is administered topically on skin or scalp or can be administered as otic drops.
In further embodiment, the stable topical formulation comprises pharmaceutically acceptable cosolvent and surfactant.
In an embodiment, the cosolvent is isopropyl alcohol whereas surfactant is isopropyl myristate.
In another embodiment, the present invention relates to a stable topical pharmaceutical composition comprising therapeutically effective amount of Fluocoinolone acetonide and organic acid wherein the organic acid is lactic acid, benzoic acid, tartaric acid, maleic acid or citric acid.
In further embodiment, the stable topical composition comprises organic acid in the range of 0.001 to 0.1%w/w as stabilizer.
In another embodiment, the stable topical composition comprises citric acid as stabilizer organic acid.
In yet another embodiment, ratio of citric acid to fluocinolone acetonide ranges from 0.01 to 10.
In an embodiment, the present invention relates to a topical pharmaceutical composition of therapeutically effective amount of Fluocoinolone acetonide comprising isopropyl alcohol, isopropyl myristate, polyethylene glycol ether of Oleyl Alcohol (Oleth®-2), peanut oil, light mineral oil and citric acid which is stable on storage.
In yet another embodiment, the present invention relates to a method of treating, managing or preventing a dermatological condition selected from group consisting of skin condition or scalp condition comprising administering the stable topical Fluocinolone acetonide oil, in a patient in need thereof.
In further embodiment, wherein the dermatological condition is atopic dermatitis or psoriasis.
In yet another embodiment, the present invention relates to a method of treating, managing or preventing otic inflammation comprising administering the stable topical Fluocinolone acetonide oil, in a patient in need thereof.
In further embodiment, the otic inflammation is diffuse external otitis, localized external otitis, chronic eczematous external otitis, traumatic tympanic membrane perforations, herpes zoster oticus, otitis media with effusion, otorrhea through tympanostomy tubes, acute otitis media with tympanostomy tubes, acute otitis media or chronic otitis media

DETAILED DESCRIPTION OF THE INVENTION
The terms used herein are defined as follows. If a definition set forth in the present application and a definition set forth later in a non-provisional application claiming priority from the present provisional application are in conflict, the definition in the non-provisional application shall control the meaning of the terms.
The term singular forms "a," "an" and "the" include plural references unless the context clearly dictates otherwise. Thus, for example, reference to "an excipient" includes a single excipient as well as two or more different excipients, and the like.
The term "Fluocinolone acetonide" refers to fluocinolone acetonide, its hydroxylated forms, hydrates, solvates, polymorphic forms, analogs, derivatives, esters, complex, cocrystals, cogeners and prodrugs thereof.
The term "effective amount" or "therapeutically effective amount" denotes an amount of an active ingredient that, when administered to a subject for treating respiratory disorders, produces an intended therapeutic benefit in a subject. The term “active ingredient” (used interchangeably with “active” or “active substance” or “drug”) as used herein includes fluticasone furoate and tiotropium bromide or pharmaceutically acceptable hydrates thereof.
The term “treating” or “treatment” as used herein also covers the prophylaxis, mitigation, prevention, amelioration, or suppression of a disorder modulated by fluocinolone acetonide in a mammal.
The term "subject" includes mammals like human and other animals, such as domestic animals (e.g., household pets including cats and dogs) and non-domestic animals (such as wildlife). Preferably, the subject is a human.
By “pharmaceutically acceptable excipients”, it is meant any of the components of a pharmaceutical composition other than the actives and which are approved by regulatory authorities or are generally regarded as safe for human or animal use.
The term “non-aqueous" means that the composition contains no, or essentially no (e.g., 0- 20 % w/w, preferably 20, 10, 5, 3, 2, 1, 0.5, 0.2% w/w or less), free or unassociated or absorbed water.
The term “stabilizer or stabilizing agent” refers to the excipient or ingredient which tends to inhibit the reaction between two or more other chemicals or which is added to the formulation for the purpose of long term storage without loss of functional activity preventing the degradation of the product.
The present patent application relates to a stable topical pharmaceutical composition comprising therapeutically effective amount of Fluocoinolone acetonide and organic acid.
The therapeutically effective amount of Fluocinolone acetonide to be administered per day is less than 1 % by weight and more particularly that the compositions comprises Fluocinolone acetonide between 0.005 % and 0.1% by weight.
In an embodiment, the present invention relates to a stable topical pharmaceutical composition comprising therapeutically effective amount of Fluocoinolone acetonide and organic acid wherein the formulation is oil based system.
The topical oil formulation as per present invention may contain blend of oils. Examples of oils include but not limiting to isopropyl alcohol, isopropyl myristate, light mineral oil, refined peanut oil etc.
In another embodiment, the present invention relates to a stable topical pharmaceutical composition comprising therapeutically effective amount of Fluocoinolone acetonide and organic acid wherein formulation is administered topically on skin or scalp or can be administered as otic drops.
The pharmaceutical composition in the above embodiments may optionally comprise one or more pharmaceutically acceptable excipients.
According to present invention the topical oil may comprise excipients such as cosolvent, solubilizers, emulsifiers, surfactants, fragrances, stabilizer, anti-oxidants etc
In further embodiment, the stable topical formulation comprises pharmaceutically acceptable cosolvent and surfactant.
Co-solvent is any solvent which is miscible in the formulation in the amount desired and which, when added, provides a formulation in which the medicament can be dissolved. The function of the cosolvent is to increase the solubility of the medicament and the excipients in the formulation.
According to the present invention the co-solvent may comprise one or more of, C2- C6 aliphatic alcohols, such as but not limited, to ethyl alcohol and isopropyl alcohol; glycols such as but not limited to propylene glycol, polyethylene glycols, polypropylene glycols, glycol ethers, and block copolymers of oxyethylene and oxypropylene; and other substances, such as but not limited to glycerol, polyoxyethylene alcohols, and polyoxyethylene fatty acid esters; hydrocarbons such as, but not limited to, n-propane, n-butane, isobutane, n-pentane, iso-pentane, neo-pentane, and n-hexane; and ethers such as but not limited to diethyl ether. Isopropyl alcohol can be used as co-solvent in the range of 1-5% w/w
According to the present invention the surfactant may comprise one or more ionic and/or non-ionic surfactant, but not limited to, salts of stearic acids such as magnesium stearate or esters such, as ascorbyl palmitate, isopropyl myristate and tocopherol esters oleic acid, sorbitan trioleate, lecithin, isopropylmyristate, tyloxapol, polyvinylpyrrolidone, polysorbates such as polysorbate 80, Polysorbate 20, Polysorbate 40, vitamin E-TPGS, and macrogol hydroxystearates such as macrogol- 15-hydroxystearate, acetylated monoglycerides like Myvacet 9-45 and Myvacet 9-08, Polyoxyethylene ethers, ethyloleate, glyceryl trioleate, glyceryl monolaurate, glyceryl monooleate, glyceryl monosterate, glyceryl monoricinoleate, cetylalcohol, sterylalcohol, cetylpyridinium chloride, block polymers, natural oils, polyvinyl pyrrolidone (PVP), sorbitan fatty acid esters such as sorbitan trioleate, polyethoxylated sorbitan fatty acid esters (for example polyethoxylated sorbitan trioleate), sorbimacrogol oleate, synthetic amphotensides (tritons), ethylene oxide ethers of octylphenolformaldehyde condensation products, phosphatides such as lecithin, polyethoxylated fats, polyethoxylated oleotriglycerides and polyethoxylated fatty alcohols. Isopropyl myristate can be used in the range of 2-6% w/w
The surfactants may also be selected from the vast class known in the art like oils such as, but not limited to peanut oil, corn oil, olive oil, cottonseed oil and sunflower seed oil, mineral oils like liquid paraffin, oleic acid and also phospholipids such as lecithin, or sorbitan fatty acid esters like sorbitan trioleate or Tween 20, Tween 60, Tween 80, PEG - 25 Glyceryl trioleate, PVP, PFDA (per fluoro-n-decanoic acid). Refined peanut oil can be used in the range of 40-60% w/w whereas mineral oil can be used in the range of 30-60% w/w
According to present invention, suitable buffers or pH adjusting agents may be employed comprise one or more of organic or inorganic acids such as, but not limited to, citric acid, tartaric acid, benzoic acid, lactic acid, ascorbic acid, hydrochloric acid, sulfuric acid, nitric acid, or phosphoric acid.
Suitable preservatives may be employed in the topical formulation of the present invention to protect the formulation from contamination with pathogenic bacteria.
In an embodiment, the cosolvent is isopropyl alcohol whereas surfactant is isopropyl myristate.
In another embodiment, the present invention relates to a stable topical pharmaceutical composition comprising therapeutically effective amount of Fluocoinolone acetonide and organic acid wherein the organic acid is lactic acid, benzoic acid, tartaric acid, maleic acid or citric acid.
In further embodiment, the stable topical composition comprises organic acid in the range of 0.001 to 0.1%w/w as stabilizer.
In another embodiment, the stable topical composition comprises citric acid as stabilizer organic acid.
It is also preferred that the compositions comprises less than 1 % by weight of citric acid and more particularly that the compositions comprises citric acid in the range of 0.001 to and 0.1% w/w
In another embodiment, ratio of citric acid to fluocinolone acetonide ranges from 0.01 to 10.
In an embodiment, the present invention relates to a topical pharmaceutical composition of therapeutically effective amount of Fluocoinolone acetonide comprising isopropyl alcohol, isopropyl myristate, Oleth®-2, peanut oil, light mineral oil and citric acid which is stable on storage.
In yet another embodiment, the present invention relates to a method of treating, managing or preventing a dermatological condition selected from group consisting of skin condition or scalp condition comprising administering the stable topical Fluocinolone acetonide oil, in a patient in need thereof.
In further embodiment, wherein the dermatological condition is atopic dermatitis or psoriasis.
In yet another embodiment, the present invention relates to a method of treating, managing or preventing otic inflammation comprising administering the stable topical Fluocinolone acetonide oil, in a patient in need thereof.
In further embodiment, the otic inflammation is diffuse external otitis, localized external otitis, chronic eczematous external otitis, traumatic tympanic membrane perforations, herpes zoster oticus, otitis media with effusion, otorrhea through tympanostomy tubes, acute otitis media with tympanostomy tubes, acute otitis media or chronic otitis media
The pharmaceutical composition of the present invention is administered topically on skin or scalp as oil or can be administered as otic drops.
The process for making the pharmaceutical composition as described, the process comprises the step of charging refined peanut oil, light mineral oil, Isopropyl myristate & Oleth®-2 in main the vessel. The mixture was homogenized for 15-20 min under stirring at 10-50Hz till phase becomes clear, the drug solution (fluocinolone acetonide drug phase was added in isopropyl alcohol under stirring till complete solubilization) was added to oil phase under stirring. The drug phase vessel was rinsed with Isopropyl myristate. After homogenization under continuous stirring for 30min, it was filled and supplied in bottles.
As per table 1, fluocinolone acetonide topical oil formulation was developed comprising isopropyl alcohol, isopropyl myristate, light mineral oil, Oleth®-2, refined peanut oil.
Table 1 Formulation development example1
# Ingredients Qty (%w/w)
1 Fluocinolone acetonide 0.011
2 Isopropyl alcohol 1.43
3 Isopropyl myristate 3
4 Refined peanut oil NF 52
5 Oleth®-2 4.4
6 Light mineral oil 39.059
We have found that the drug substance “Fluocinolone Acetonide “is prone to degradation when incorporated in the topical oil formulation. The commonly found impurities were
1) 21-acid analog (Impurity A or Imp A)
2) 17 ß-acid analog (Impurity B or Imp B)
3) 21-aldheyde analog (Impurity D or Imp D)
It was observed that impurities were generated due to degradation of Fluocinolone acetonide. The challenge was with respect to batch to batch variation in impurity content in the samples after storage. Table 2 discloses various impurities generated in different lots of the formulation when initial stability testing is conducted at room temperature. 7 batches of the formulation prepared according to table 1 were analyzed for impurity content and it was observed that the amount of impurities A, B and D were different in different batches. Moreover total impurity content was also found to be variable.
Table 2 – Batch comparison of impurity content
21 Acid analog 17 B Acid Analog
21 Aldehyde Analog Total Impurity (Imp)
(Imp A) (Imp B) (Imp D)
Batch 1 0.08 0.19 ND 1.04
Batch 2 0.09 0.28 ND 0.54
Batch 3 0.24 1.04 0.23 2.64
Batch 4 0.25 1.51 0.13 2.84
Batch 5 0.48 1.34 0.11 3.28
Batch 6 0.31 0.18 ND 0.66
Batch 7 0.62 0.6 1.05 3.19
On further stability studies were conducted at 600 C for 7 days. Table 3 shows the comparative impurity content of API alone along with combination of other excipients from the formulation tested at 60oC for 7 days. It was observed that out of all the excipients used in the formulation as mentioned in table 1 such as mineral oil, isopropyl alcohol, Oleth®-2, peanut oil and isopropyl myristate; impurities generated by presence of Oleth® -2 are higher in amount.
Table 3 – Comparative impurity data of Fluocinolone acetonide with different excipients
Product Details Stability
condition Time period 21 Acid analog
(Imp A) 17 B Acid Analog (Imp B) 21 Aldehyde Analog (Imp D) Total imp
API 60°C Initial ND ND 0.14 0.37
7 Days ND 0.01 0.15 0.42
API
+ Light Mineral Oil 60°C Initial ND 0.02 0.16 0.37
7 Days ND 0.01 0.16 0.37
API
+ Oleth®-2 [CRODA] 60°C Initial ND 0.15 ND ND
7 Days 3.39 8.46 ND 16.92
40°C/ 75%RH 1M 3.77 6.19 BLQ 17.35
API
+ Isopropyl Alcohol 60°C Initial ND 0.01 0.09 0.39
7 Days ND 0.27 0.13 1.26
API + Isopropyl Myristate 60°C Initial ND 0.03 0.14 0.37
7 Days ND 0.02 0.16 0.4
API + Peanut oil 60°C Initial ND 0.00 0.13 0.35
7 Days ND 0.01 0.01 0.4
In order to prepare the stable topical oil formulation, various stabilizing agents were explored to prevent this oxidation reaction of Fluocinolone acetonide. Anti-oxidants such as Butylated hydroxyl anisole (BHA) and butylated hydroxyl toluene (BHT); or organic acids such as citric acid, maleic acid, benzoic acid nitric acid etc were tested for stability studies.
Table 4 illustrates examples of formulations comprising use of anti-oxidants or organic acids in different quantities.
Table 4 –Examples with use of stabilizing agents
Example 2
%w/v Example 3
%w/v Example 4
%w/v Example 5
%w/v Example 6
%w/v Example 7
%w/v
Fluocinolone Acetonide 0.01 0.01 0.01 0.01 0.01 0.01
Isopropyl alcohol 1.26 1.26 1.26 1.26 1.26 1.26
Isopropyl Myristate 13.5 13.5 13.5 13.5 13.5 13.5
Oleth®-2 3 3 3 3 3 3
Citric acid anhydrous - 0.01 - - - -
Refined Peanut oil 48 44 48 48 48 48
BHT 0.01 - - - - -
Lactic acid - 0.1 - - -
Benzoic Acid 0.1 - -
Tartaric acid 0.1 -
Maleic Acid 0.1
Light mineral oil q.s. to 100 ml q.s. to 100 ml q.s. to 100 ml q.s. to 100 ml q.s. to 100 ml q.s. to 100 ml
All the formulations were tested for stability at 60oC for 7 days for the impurity content.
Use of organic acid decreased the impurity content as compared to formulations without stabilizers. Among all the organic acids tested, comparative stress stability data showed that formulation with citric acid and maleic acid generated lesser impurities as compared to formulations comprising other stabilizing agents.
Table 5 Comparative stability data of all the formulations at 60oC for 7 days
Product Details Stability
condition Time period 21 Acid analog
(Imp A) 17 B Acid Analog (Imp B) 21 Aldehyde Analog (Imp D) Total imp
Example 2 60°C Initial BLQ 0.08 BLQ 0.49
7 Days 0.78 1.2 BLQ 3.26
Example 3 60°C Initial ND 0.06 ND 0.73
7 Days 0.07 0.08 ND 0.35
Example 4 60°C Initial ND ND 0.1 2.17
7 Days 0.26 0.71 ND 3.24
Example 5 60°C Initial 0.06 0.07 0.12 0.48
7 Days 3.13 4.17 ND 12
Example 6 60°C Initial 0.08 0.09 0.05 0.54
7 Days 0.46 0.79 ND 2.21
Example 7 60°C Initial ND ND 0.11 0.16
7 Days ND 0.12 BLQ 0.3

Table 6 Examples of the formulation comprising citric acid
Composition Example 8
(%w/w) Example 9
(%w/w) Example 10
(%w/w) Example 11
(%w/w)
Fluocinolone Acetonide 0.011 0.011 0.011 0.011
Isopropyl alcohol 1.43 1.43 1.43 1.43
Isopropyl Myristate 3 4.5 6 4.5
Oleth-2 2.4 3.4 2.4 3.4
Refined peanut oil 48 48 52 48
Light Mineral oil 45.059 42.649 38.059 42.649
Citric acid 0.001 0.005 0.01 0.025

Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and application of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as described above.
All publications, patents, and patent applications cited in this application are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated herein by reference.

We claim:
1. A stable topical pharmaceutical composition comprising therapeutically effective amount of Fluocoinolone acetonide or salts thereof and a stabilizing agent
2. The pharmaceutical composition according to claim 1, wherein therapeutically effective amount of Fluocoinolone acetonide or salts thereof is present in amount of 0.005 % to 0.1% by weight of the composition
3. The pharmaceutical composition according to claim 1, wherein the stabilizing agent is an organic acid
4. The composition according to claim 3, wherein the organic acid is selected from group consisting of lactic acid, benzoic acid, tartaric acid, maleic acid and citric acid
5. The composition according to claim 4, wherein the organic acid is citric acid
6. The composition according to claim 3, wherein the formulation comprises organic acid in an amount of 0.001 to 0.2% w/w of the composition.
7. The pharmaceutical composition according to claim 3, wherein the ratio of organic acid to fluocinolone acetonide ranges from 0.01 to 10.
8. The pharmaceutical composition according to claim 1, wherein the formulation is an oil based system administered topically on skin or scalp or can be administered as otic drops
9. A topical pharmaceutical composition of therapeutically effective amount of Fluocoinolone acetonide or salts thereof comprising isopropyl alcohol, isopropyl myristate, Polyoxyl 2 oleyl ether, peanut oil, light mineral oil and citric acid wherein the formulation is stable on storage at an accelerated stability condition of 40°C temperature and 75% relative humidity.
10. The composition according to claim 9, wherein the formulation is used for the treatment of dermatological condition comprising atopic dermatitis or psoriasis for the patients in need thereof

Dated this 16th day of February 2018

Signature________________________
Taranpreet S. Lamba
Vice President,
Intellectual Property& Portfolio Management
Glenmark Pharmaceuticals Ltd., Mumbai

ABSTRACT
The present invention relates to pharmaceutical composition comprising Fluocinolone acetonide. Particularly, the invention relates to an oil composition for topical administration comprising therapeutically effective amount of Fluocinolone acetonide, a process for preparing the stable pharmaceutical composition and method of treating otic inflammation or skin disorders.

,CLAIMS:We claim:
1. A stable topical pharmaceutical composition comprising therapeutically effective amount of Fluocoinolone acetonide or salts thereof and a stabilizing agent
2. The pharmaceutical composition according to claim 1, wherein therapeutically effective amount of Fluocoinolone acetonide or salts thereof is present in amount of 0.005 % to 0.1% by weight of the composition
3. The pharmaceutical composition according to claim 1, wherein the stabilizing agent is an organic acid
4. The composition according to claim 3, wherein the organic acid is selected from group consisting of lactic acid, benzoic acid, tartaric acid, maleic acid and citric acid
5. The composition according to claim 4, wherein the organic acid is citric acid
6. The composition according to claim 3, wherein the formulation comprises organic acid in an amount of 0.001 to 0.2% w/w of the composition.
7. The pharmaceutical composition according to claim 3, wherein the ratio of organic acid to fluocinolone acetonide ranges from 0.01 to 10.
8. The pharmaceutical composition according to claim 1, wherein the formulation is an oil based system administered topically on skin or scalp or can be administered as otic drops
9. A topical pharmaceutical composition of therapeutically effective amount of Fluocoinolone acetonide or salts thereof comprising isopropyl alcohol, isopropyl myristate, Polyoxyl 2 oleyl ether, peanut oil, light mineral oil and citric acid wherein the formulation is stable on storage at an accelerated stability condition of 40°C temperature and 75% relative humidity.
10. The composition according to claim 9, wherein the formulation is used for the treatment of dermatological condition comprising atopic dermatitis or psoriasis for the patients in need thereof