FORM 2
THE PATENTS ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION:
"TOPICAL FORMULATION CONTAINING HALOBETASOL PROPIONATE
AND TAZAROTENE'
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-Kuria 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:

TECHNICAL FIELD OF INVENTION:
The present invention relates to a topical pharmaceutical composition comprising combination of therapeutically effective amount of high potency corticosteroid such as Halobetasol propionate and retinoid such as Tazarotene, useful for the treatment of different types of psoriasis such as Plaque Psoriasis, Guttate Psoriasis, Seborrheic Psoriasis, Palmoplantar Psoriasis, Pustular Psoriasis, Palmoplantar Pustulosis or Acropustulosis Erythrodermic Psoriasis, Inverse Psoriasis or Flexural Psoriasis. The invention further relates to process for preparation thereof.
BACKGROUND OF THE INVENTION:
Proliferative skin diseases are widespread throughout the world and afflict millions of humans. The expression "proliferative skin diseases" means benign and malignant proliferative skin diseases which are characterized by accelerated cell division in the epidermis, dermis or appendages thereto, associated with incomplete tissue differentiation. Such diseases includes psoriasis, atopic dermatitis, non-specific dermatitis, primary irritant contact dermatitis, allergic contact dermatitis, basal and squamous cell carcinomas of the skin, lamellar ichthyosis, epidermolytic hyperkeratosis, premalignant sun induced keratosis, non-malignant kertosis. acne and seborrheic dermatitis in humans.
Among other proliferative skin diseases; psoriasis is a chronic skin disorder that affects 2-4% of the population world-wide.
As psoriasis is a nonfatal disease, its profound impact on the overall quantity of life and well-being is often underestimated. It has a significant effect on the physical, social, psychological and financial avenues of life and an early and aggressive treatment is required to prevent disease progression.
Many patients require life-long treatments for repeated relapses. Treatments for psoriasis have thus far included topicals (including anthralin), steroids, vitamin D, analogues and retinoids. Such as tazarotene and other forms of treatment include systemic

immunosuppressant such as methotrexate and cyclosporin, phototherapy such as broad and narrow-band ultraviolet Type B (UVB) and Goeckerman treatment, which is a combination of tar and UVB therapy. Recently a new class of drugs, the biologies, has also been approved for the treatment of psoriasis.
Though monotherapies are effective for the treatment of psoriasis, evidences are accumulating that combining topical retinoid, specifically Tazarotene with other established antipsoriatic therapies result in enhanced efficacy and reduced adverse events. In particular, concomitant use of topical Tazarotene with a mid-potency or high-potency corticosteroid in the treatment of psoriatic plaques enhances efficacy and reduces the risk of corticosteroid skin atrophy. The results of completed Phase III clinical trials of this agent indicate a beneficial effect in moderate to severe plaque psoriasis.
Retinol have been defined narrowly as comprising vitamin A (retinol) and its derivatives, such as vitamin A aldehyde (retinal) and vitamin A acid (retinoic acid), which are metabolites of natural vitamin A. However, subsequent research has resulted in a larger class of chemical compounds that are termed retinoids because they have biological actions similar to the parent vitamin A, even though there may be great structural dissimilarities. Thus, Retinol (Vitamin A) is an organic molecule that is not synthesized in the body; therefore, it must be obtained from the diet, as either preformed retinol or its precursor beta carotene, which is then converted in vivo into retinol.
Further, Retinol binds to several retinoic acid receptors in the nucleus, including a, β and Y with receptor y being the predominant in human epidermis. Tazarotene is a vitamin A derivative that is converted in vivo into its active agent, Tazarotene acid, which binds to all three retinoic acid receptors with particularly increased selectivity for receptors β and y. It has little affinity for the retinoic X receptors.
Tazarotene is mainly used for the treatment of psoriasis, acne vulgaris and sun damaged skin (photodamage). Tazarotene induces the expression of tazarotene-induced gene 3 (TIG3), a tumor suppressor gene. In psoriasis, Tazarotene acid normalizes abnormal keratinocyte differentiation, decreases expression of inflammatory markers and reduces keratinocyte hyperproliferation. Thus, it is very useful as an anti-psoriatic agent.

Chemically, Tazarotene is ethyl 6-[2-(4,4-dirnethyl-3,4-dihydro-2H-l-benzothiopyran-6-yl)ethynyl]pyridine-3-carboxylate It has the following structural formula:

Further, like other topical corticosteroids, Halobetasol propionate has anti-inflammatory, antipruritic and vasoconstrictive actions. The mechanism of the anti-inflammatory activity of the topical corticosteroids, 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.

Chemically, Halobetasol propionate is 21-chloro-6α, 9-difluoro-llβ, 17-dihydroxy-l6β-. methylpregna-1, 4-diene-3-20-dione, 17-propionate. C25H31CIF2O5. It has the following structural formula:
Moreover, methods for the treatment of inflammatory
dermatoses by administering topical compositions comprising a corticosteroid such as clobetasol propionate, triamcinolone acetonide and hydrocortisone along with a retinoid such as tretinoin in amounts which are effective for treating the dermatoses is disclosed in US5998395.

US2004192662 provides a method for treating proliferative skin diseases comprising the administration of an effective amount of Tazarotene and an effective amount of a corticosteroid (mometasone furoate and fluocinolone acetonide) useful for treating psoriasis.
Indian Patent Application No.I74I/MUM/2007 (corresponding PCT Publication no WO2009063491) relates to process for preparation of topical compositions comprising arbutin, corticosteroid (triamcinolone or desonide), retinoid (tretinoin) and optionally a sun protection factor (SPF) for the treatment of skin diseases includes melasma, ephelides, post inflammatory hyperpigmentation, dermal blemishes, non-congenital hyperpigmentation, and solar lentigo.
An article titled "In vitro compatibility of tazarotene with other topical treatments of psoriasis" by Hecker D, Worsley J, Yueh G, Lebwohl M., discloses the compatibility of tazarotene gel with 15 other topical steroids of different potencies, used in the treatment of psoriasis.
An article titled "Tazarotene 0.1% gel plus corticosteroid cream in the treatment of plaque psoriasis" by Lebwohl et al discloses a combination of 0.1% tazarotene gel with either placebo, low potency steroid (0.01%) fluocinolone acetonide cream), mid-potency steroid (0.1%) mometasone furoate cream) or high-potency steroid (0.05% fluocinonide cream). The said article illustrated that 0.1% Tazarotene gel once-daily in combination with once-daily application of mid- or high-potency topical steroid achieved a significantly greater reduction in scaling, erythema and overall lesion severity than tazarotene once-daily with placebo. Similar studies by Tanghetti et al. and Gollnick et al. confirmed that the use of mid- and high-potency steroids can enhance the efficacy of tazarotene in significantly improving psoriasis.
An article titled "The efficacy of topical tazarotene monotherapy and combination therapies in psoriasis" by John Koo et al discloses tazarotene in combination with 0.05% diflorasone diacetate which gives reduction of 28% in the epidermal thickness. Further, tazarotene significantly reduced epidermal atrophy induced by 0.05% diflorasone diacetate.

An article titled "Evaluating the potential clinical benefits of switching patients with plaque psoriasis from caicipotriene to tazarotene treatment" by Coynik D compare the effects of 0-1% tazarotene gel combined with a topical corticosteroid to caicipotriene combined with a topical corticosteroid. The authors concluded that switching patients from caicipotriene to tazarotene could increase efficacy and patient satisfaction.
Thus, in light of above; though there are prior arts describing corticosteroids and retinoids in combination, none of them has specifically evaluated the benefits and effect of the combination comprising Halobetasol propionate and Tazarotene simultaneously.
Accordingly, the present invention discloses an effective combination comprising Halobetasol propionate and Tazarotene useful for treating different types of psoriasis such as Plaque Psoriasis, Guttate Psoriasis, Seborrheic Psoriasis, Palmoplantar .Psoriasis, Pustular Psoriasis, Palmoplantar Pustulosis or Acropustulosis Erythroderma Psoriasis. Inverse Psoriasis or Flexural Psoriasis. Though these two drugs have entirely different modes of action and when combined in a single formulation, have synergistic effects which lead to more rapid clearing and are notably effective for types of psoriasis which have not responded to either corticosteroids or retinoids alone.
OBJECT OF THE INVENTION:
The main object of the current invention is to provide the topical composition comprising Halobetasol propionate and Tazarotene. useful for the treatment of different types of psoriasis such as Plaque Psoriasis, Guttate Psoriasis, Seborrheic Psoriasis, Palmoplantar Psoriasis, Pustular Psoriasis, Palmoplantar Pustulosis or Acropustulosis Erythrodermic Psoriasis, Inverse Psoriasis or F/exuraf Psoriasis and process for preparation thereof.
SUMMARY OF THE INVENTION:
In accordance with the above objective, the present invention discloses topical composition comprising of high potency corticosteroid such as Halobetasol propionate and retinoid such as Tazarotene having synergistic effect against different types of

psoriasis such as Plaque Psoriasis, Guttate Psoriasis. Seborrheic Psoriasis, Palmoplantar Psoriasis, Pustular Psoriasis, Palmoplantar Pustulosis or Acropustulosis Erythrodermic Psoriasis, Inverse Psoriasis or Flexural Psoriasis.
In further aspect, the present invention provides a process for preparation of said composition.
In yet another aspect, the present invention provides the said combination in different dosage forms such as cream, ointment, gel or lotion.
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 composition for the treatment of different types of psoriasis such as Plaque Psoriasis, Guttate Psoriasis, Seborrheic Psoriasis, Palmoplantar Psoriasis, Pustular Psoriasis, Palmoplantar Pustulosis or Acropustulosis Erythrodermic Psoriasis, Inverse Psoriasis or Flexural Psoriasis which comprises of Halobetasol propionate a synthetic corticosteroid and Tazarotene a retinoid in the form of cream, ointment, gel or lotion.
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.
More particularly, the present invention provides the topical composition comprising therapeutically effective amount of Halobetasol propionate and Tazarotene along with pharmaceutically acceptable excipients.
In one of the embodiment, the topical cream/ointment formulation comprises Halobetasol propionate (0.025 to 0.05% w/w) and Tazarotene (0.05 to 0.1% w/w) along with the

pharmaceutical excipients selected from the group comprising of ointment/cream base like waxes, preservatives, antioxidants, buffering agent, chelating agent penetration enhancer, surfactant, solubilizer, emulsifier and combinations thereof.
According to the embodiment, the topical cream of Halobetasol propionate and Tazarotene, is prepared using excipients selected from the group consisting of Cetostearyl alcohol, Cetomacrogol 1000, Light liquid paraffin, White soft paraffin, Chlorocresol, Butylated hydroxy toluene, Propylene glycol, Hexylene glycol, Disodium EDTA and Citric acid.
According to another embodiment, the ointment of Halobetasol propionate and Tazarotene is prepared using excipients selected from the group consisting of Butylated hydroxy toluene, Sorbitan sesquioleate. Propylene glycol, Hexylene glycol, White soft paraffin, White bees wax. Cetyl alcohol, Lanolin anhydrous and Liquid paraffin.
According to the invention, the topical composition of Halobetasol propionate and Tazarotene is in the form of cream that can be prepared by melting oil base excipients, emulsifier and optionally antioxidant; followed by dissolving chelating agent in sufficient quantity of purified water; mixing oil phase and water phase under stirring for the emulsion formation at 60-70°C; this is followed by adding preservatives dissolved in solubilizer, penetration enhancer, etc.; followed by cooling and stirring, till stable cream formation takes place. Active ingredient dissolved in Solubilizer can be added before cream formation or while the cream formation is taking place.
According to the invention, the topical composition of Halobetasol propionate and Tazarotene . is in the form of ointment that can be prepared by melting ointment base excipients and mixing surfactant to ointment base; adding active ingredient either by dissolving or suspending in solubilizer under constant stirring; cooling and stirring the till ointment formation takes place.
In further embodiment, the topical gel/lotion formulation comprises Halobetasol propionate (0.025 to 0.05% w/w) and Tazarotene (0.05 to 0.1% w/w) along with pharmaceutical excipients selected from the group comprising oil base, preservatives,

antioxidants, buffering agent, chelating agent, penetration enhancer, co-solvent, Carbopol, pH adjuster along with vehicle, surfactant, solubilizer, emulsifier and combinations thereof.
Further, the gel of Halobetasol propionate and Tazarotene is prepared using excipients selected from the group consisting of Carbopol 980, Carbopol 940; Hydroxy Propyl Cellulose, Disodium EDTA, Banzyl Alcohol ,Chlorocresol, Butylated Hydroxytoluenen, Ascorbic Acid, Sodium Sulphide, Sodium Metabisulphite, Propylene glycol. Citric acid, Sodium Citrate, Triethanolamine, Sodium Hydroxide, Diethanolamine, Purified Water and Isopropyl alcohol.
According to the present invention, the topical composition of Halobetasol and Tazarotene is in the form of gel that can be prepared by soaking carbopol 980 slurry in sufficient quantity of purified water; dissolving chelating agent in sufficient quantity of purified water and adding Co carbopol slurry; adding active ingredients and preservative dissolving or dispersing in solubilizer; this is followed by adding Isopropyl alcohol under stirring; checking the pH and adjusting the pH around 4.0 to 6.0 with 20% triethanolamine (TEA) or Diethanolamine or sodium hydroxide solution, till gel formation takes place.
According to another preferred embodiment, the lotion of Halobetasol propionate and Tazarotene is prepared using excipients selected from the group consisting of Cetyl alcohol, Sodium Lauryl Sulphate, Propylene glycol, Polyethylene Glycol 400, White soft paraffin, Butylated Hydroxytoluene, Methyl paraben, Propyl paraben and Chlorocresoi.
Further, the topical composition of Halobetasol and Tazarotene in the form of lotion is prepared by melting emulsifier, oil base and preservatives and optionally antioxidant by heating at 70-80°C; mixing oil phase and water phase under stirring for the emulsion formation at 60-70°C; followed by adding surfactant etc, for the stable lotion formation. Active ingredient dissolved in solubilizer can be added before emulsion formation or while the emulsion formation is taking place.

Alternately, lotion can be prepared by dissolving Halobetasol in hot Propylene Glycol and dissolving Tazarotene in Propylene glycol in separate beakers. Simultaneously, dissolving Butylated Hydroxy Toluene in PEG 400; and then adding all the solutions into one vessel followed by mixing, till clear solution is obtained and making up the volume with propylene glycol or PEG 400.
The invention is further illustrated by following non-limiting examples of this combination product:
EXAMPLES:
Example 1:
Composition for the Preparation of Cream:

Ingredients Concentration % w/w
Active Ingredients Halobetasol propionate 0.025 - 0.05%

Tazarotene 0.05-0.1%
Emulsifiers Cetostearyl alcohol 4.2 - 7.8%

Cetomacrogol 1000 1.05- 1.95%
Oil Base Light Liquid Paraffin 2.8-5.2%

White soft Paraffin 2.8-5.2%
Penetration enhancers/ solubilizer Propylene glycol 6.3-10.2%

Hexylene glycol 7-13%
Antioxidant Butylated Hydroxy Toluene 0.01 -0.025%
Chelating agent Disodium EDTA 0.007-0.013%
Preservative Chlorocresol 0.07-0.13%
Vehicle Water q.s
Process for preparing Cream formulation is as follows:
1) Melting oil base excipients, emulsifier and optionally antioxidant;
2) dissolving chelating agent in sufficient quantity of purified water;
3) mixing oil phase and water phase under stirring for the emulsion formation at 60°-70°C;

4) dissolving or dispersing active ingredients in solubilizer and adding to bulk of step 3;
5) dissolving preservative in Solubilizer and adding it to bulk of step 4 under stirring;
6) cooling and stirring of the bulk till cream formation takes place; and
7) adjusting the weight with purified water.
Example 2:
Composition for the Preparation of Ointment:

Ingredients Concentration % w/w
Active Ingredients Halobetasol propionate 0.025 - 0.05%

Tazarotene 0.05-0.1%
Solubilizers Hexylene glycol 7-13%

Propylene glycol 7-13%
Ointment base White Soft Paraffin 54.95 - 90%

White Beeswax 21 -39%
Surfactant Sorbitan Sesquioleate 0.105-0.195%
Process for preparing Ointment formulation is as follows:
1) Melting ointment base excipients and mixing surfactant to ointment base;
2) adding active ingredients to bulk (melted ointment base) either by dissolving or dispersing in solubilizer under constant stirring; and
3) cooling and stirring the bulk till ointment formation takes place.
Example 3:
Composition for the Preparation of Lotion:

Ingredients Concentration % w/v
Active Ingredients Halobetasol propionate 0.025 - 0.05%

Tazarotene 0.05-0.1%
Oil base White Soft Paraffin 0.525 - 0.975%
Emulsifier Cetyl Alcohol 1.33 -2.47%
Solubilizer Propylene Glycol 5.25-9.75%
Antioxidant Butylated Hydroxy Toluene 0.01 -0.025%
Preservatives Methyl Paraben 0.245-0.455%

Propyl Paraben 0.035-0.065%
Surfactant Sodium Lauryl Sulphate 0.21 -0.39%
Vehicle Water q.s
Process for preparing Lotion formulation is as follows:
1) Melting emulsifier, oil base, and preservatives and optionally antioxidant by heating at 70-80°C;
2) mixing oil phase and sufficient water phase under stirring for the emulsion formation at 60°-70°C;
3) dissolving or dispersing active ingredients in solubilizer;
4) adding active drug either before emulsion formation or during emulsion formation;
5) dissolving surfactant in sufficient purified water and then adding to bulk;
6) cooling and stirring the bulk till lotion formation takes place and then making up the volume.
Alternate composition for the Preparation of Lotion:

Ingredients Concentration % w/v
Active Ingredients Halobetasol propionate 0.025 - 0.05%
Tazarotene 0.05-0.1%
Solubilizer PEG 400 40.25 - 74.75%
Antioxidant Butylated Hydroxy Toluene 0.014-0.026%
Solubilizer Propylene Glycol q.s
Alternate process for preparing Lotion formulation is as follows:
1) Dissolving Halobetasol in hot Propylene Glycol;
2) In a separate beaker dissolving Tazarotene in Propylene glycol;
3) dissolving Butylated hydroxy toluene in PEG 400:
4) adding all the solutions into one vessel, mixing well till clear solution is obtained and making up the volume with propylene glycol or PEG 400

Example 4:
Composition for the Preparation of Gel:

Ingredients Concentration % w/w
Active Ingredients Halobetasol propionate 0.025 - 0.05%
Tazarotene 0.05-0.1%
Gelling agent Carbopol 980 0.595- 1.105%
Chelating agent Disodium EDTA 0.035 -0.065%
Penetration Enhancer/Solubilizer Propylene Glycol 21 - 39%
Preservative Benzyl Alcohol 0.3-1.3%
Vehicle Isopropyl Alcohol 7- 13%
Vehicle Water q.s
pH adjusting agent TEA 20% solution q.s
Process for preparing Gel formulation is as follows:
1) Preparing carbopol 980 slurry in sufficient quantity of purified water;
2) dissolving chelating agent in sufficient quantity 0f purified water and adding to carbopol slurry of step 1;
3) dissolving Halobetasol propionate in solubilizer and adding to bulk of step 2;
4) dissolving Tazarotene in Benzyl alcohol and adding to bulk of step 3:
5) adding Isopropyl alcohol to the bulk of step 4 under stirring:
6) checking the pH and adjusting pH with 20% pH adjusting agent about 4.0 to 6.0 till gel formation takes place;
7) adjusting the final weight with purified water and mixing well.
Overages of Halobetasol propionate and Tazarotene can be added for the long term stability purpose.

STABILITY DATA:
Stability study of the product is carried out as per ICH guideline for 6 months at accelerated condition of 40°C / 75% RH and real time condition of 30°C / 65%RH. Product is stable.

We Claim,
1. A topical pharmaceutical composition comprising Halobetasol propionate and Tazarotene in therapeutically effective amounts along with pharmaceutically acceptable excipients; useful for the treatment of different types of psoriasis such as Plaque Psoriasis, Guttate Psoriasis, Seborrheic Psoriasis, Palmoplantar Psoriasis, Pustular Psoriasis, Palmoplantar Pustulosis or Acropustulosis Erythroderma Psoriasis, Inverse Psoriasis or Flexural Psoriasis.
2. The topical pharmaceutical composition as claimed in claim 1, wherein the Halobetasol propionate is present in an amount of 0.025 to 0.05%.
3. The topical pharmaceutical composition as claimed in claim 1, wherein the Tazaroten is present in an amount of 0.05 to 0.1%.
4. The topical pharmaceutical composition as claimed in claim 1, wherein the composition is in the form of cream, ointment, gel or lotion.
5. The topical pharmaceutical composition as claimed in claim 4, wherein the cream formulation contains pharmaceutically acceptable excipients selected from the group consisting of Cetostearyl alcohol, Cetomacrogol 1000, Light liquid paraffin White soft paraffin, Chlorocresol, Butylated hydroxy toluene. Propylene glycol, Hexylene glycol, Disodium EDTA and Citric acid.
6. The topical pharmaceutical composition as claimed in claim 4, wherein the ointment contains pharmaceutically acceptable excipients selected from the group consisting of Butylated hydroxy toluene, Sorbitan sesquioleate, Propylene glycol, Hexylene glycol, White soft paraffin, White bees wax, Cetyl alcohol, Lanolin anhydrous and Liquid paraffin.
7. The topical pharmaceutical composition as claimed in claim 4, wherein the gel formulation contains pharmaceutically acceptable excipients selected from the group consisting of Carbopol 980, Carbopol 940; Hydroxy propyl cellulose,

Disodium EDTA. Banzyl Alcohol, Chlorocresol, Butylated Hydroxytoluenen. Ascorbic acid, Sodium sulphide, Sodium metabisulphite, Propylene glycol, Citric acid, Sodium citrate, Triethanolamine, Sodium hydroxide, Diethanolamine, Purified water and Isopropyl alcohol.
8. The topical pharmaceutical composition as claimed in claim 4, wherein the lotion contains pharmaceutically acceptable excipients selected from the group consisting of Cetyl alcohol, Sodium lauryl sulphate, Propylene glycol, Polyethylene Glycol 400, White soft paraffin, Butylated Hydroxy toluene, Methyl paraben, Propyl paraben and Chlorocresol.
9. The topical pharmaceutical composition as claimed in any one of the claims 1 to 4, wherein the cream formulation is prepared by,

a) Melting oil base excipients, emulsifier and optionally antioxidant;
b) dissolving chelating agent in sufficient quantity of purified water;
c) mixing oil phase and water phase under stirring for the emulsion formation at 60°-70°C;
d) dissolving or dispersing active ingredients in solubilizer and adding to bulk of step
(c);
e) dissolving preservative in Solubilizer and adding it to bulk of step (d) under stirring;
f) cooling and stirring of the bulk till cream formation takes place; and
g) adjusting the weight with purified water.
10. The topical pharmaceutical composition as claimed in any one of the claims 1 to
4, wherein the ointment is prepared by,
a) Melting ointment base excipients and mixing surfactant to ointment base;
b) adding active ingredients to bulk (melted ointment base) either by dissolving or dispersing in solubilizer under constant stirring; and
c) cooling and stirring the bulk till ointment formation takes place.

11. The topical pharmaceutical composition as claimed in any one of the claims I to
4, wherein the gel formulation is prepared by,
a) Preparing carbopol 980 slurry in sufficient quantity of purified water;
b) dissolving chelating agent in sufficient quantity of purified water and adding to carbopol slurry of step (a);
c) dissolving Halobetasol propionate in solubilizer and adding to bulk of step (b);
d) dissolving Tazarotene in Benzyl alcohol and adding to bulk of step (c):
e) adding IPA to the bulk of step (d) under stirring;
f) checking the pH and adjusting pH with 20% pH adjusting agent about 4.0 to 6.0 till gel formation takes place;
g) adjusting the final weight with purified water and mixing well.
12. The topical pharmaceutical composition as claimed in any one of the claims 1 to
4, wherein the lotion is prepared by,
a) Melting emulsifier, oil base, preservatives and optionally antioxidant by heating at 70-80°C;
b) mixing oil phase and sufficient water phase under stirring for the emulsion formation at 60°-70°C;
c) dissolving or dispersing active ingredients in soiubilizer;
d) adding active drug either before emulsion formation or during emulsion formation;
e) dissolving surfactant in sufficient purified water and then adding to bulk:
f) cooling and stirring the bulk till lotion formation takes place and then making up the volume.

13. The topical pharmaceutical composition as claimed in any one of the claims 1 to 4, wherein the lotion is alternately prepared by,
a) Dissolving Halobetasol in hot Propylene glycol;
b) In a separate beaker dissolving Tazarotene in Propylene glycol;
c) dissolving Butylated hydroxy toluene in PEG 400;
d) adding all the solutions into one vessel and mix well till clear solution is obtained and making up the volume with propylene glycol or PEG 400