Title of Invention	METHOTREXATE TOPICAL SEMISOLID DOSAGE FORM (GEL)
Abstract	Method and composition are provided for effective treatment of skin cancer and disease like psoriasis by topical application. The composition comprises a semisolid preparation of Methotrexate and the method of preparing the same is disclosed. The semisolid preparation may be preferably gel that comprise of hydrophilic gel base consisting of the gelling agent.

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FORM - 2 THE PATENTS ACT, 1970 (39 of 1970) & THE PATENTS RULES, 2003 COMPLETE (See section 10 and rule 13) METHOTREXATE TOPICAL SEMISOLID DOSAGE FORM (GEL) SANJEEV KHANDELWAL an Indian National of Prem Nivas, 13, Altamount Road, Mumbai 400 026, Maharashtra, India / u^o/^, »tf£^* ***' / * ^ THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED. 14 OCT 2005 FIELD OF INVENTION The present invention relates to formulation of Methotrexate. In particular, this invention relates to the production of a topical gel. INTRODUCTION Methotrexate is an antimetabolite used in the treatment of certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. Chemically Methotrexate is N- [4-[[(2,4-diamino-6-pteridinyl) methyl] methylamino] benzoyl]-L-glutamic acid. Molecular weight: 454.45 C20H22N8O5 and the structural formula is: Methotrexate is an antimetabolite and an analogue of folic acid. It enters the cells via an active transport system for reduced folates and, due to a relatively irreversible binding, exerts its cytotoxic effect by competitively inhibiting the enzyme dihydrofolate reductase which catalyses the conversion of folic acid to tetrahydrofolate. This interferes with the synthesis of thymidylic acid and purines, which in turn inhibits DNA synthesis and cell reproduction, and to a lesser extent protein and RNA synthesis. The affinity of dihydrofolate reductase for Methotrexate is far greater than its affinity for folic or dihydrofolic acid and, therefore, even very large 2 amounts of folic acid given simultaneously will not reverse the effects of Methotrexate. Methotrexate seems also to cause an increase in intracellular deoxyadenosine triphosphate, which is thought to inhibit ribonucleotide reduction and polynucleotide ligase, an enzyme concerned in DNA synthesis and repair. Methotrexate acts specifically on the S-phase of the cell cycle. Tissues with a high cellular proliferation rate such as neoplastic tissue, bone marrow, epithelial cells or foetal cells seem to be the most susceptible. Methotrexate is used for this reason in the treatment of psoriasis, where the rate of production of epithelial cells of the skin is much higher than that of normal cells. Methotrexate may be of value in the symptomatic control of severe, recalcitrant, disabling psoriasis, which is not adequately responsive to other forms of treatment. However, due to the high risk associated with its use, Methotrexate should be used after the diagnosis has been definitely established, as by biopsy and/or after dermatologic consultation. The patient should be fully informed of the risks involved and should be under constant supervision of the physician. Assessment of renal function, liver function and blood elements should be made by history, physical examination and laboratory tests (such as haemogram, urinalysis, serum creatinine, liver function studies and liver biopsy if indicated) before beginning Methotrexate, periodically during Methotrexate therapy and before reinstituting Methotrexate therapy after a rest period. Appropriate steps should be taken to avoid conception for at least 12 weeks following Methotrexate therapy. All schedules should be continually tailored to the individual patient. A single test dose of 5 to 10 mg parenterally one week prior to initiation of therapy is recommended to detect any idiosyncratic reaction. Contraindications: Known hypersensitivity to Methotrexate and severe renal impairment are contraindications. 3 In the treatment of psoriasis, Methotrexate is contraindicated in pregnant women and in patients with poor nutritional status, severe hepatic disorders or in those with pre-existing blood dyscrasias (such as bone marrow hypoplasia, leucopenia, thrombocytopenia or anaemia). The presence of liver impairment, alcoholism, serious infections, peptic ulcer disease or ulcerative colitis warrant extreme caution in using Methotrexate for antineoplastic therapy while they represent contraindications for its use in patients with psoriasis. Methotrexate is also contraindicated in patients with recent exposure to, recent or existing chicken pox or Herpes Zoster, and in patients with immunodeficiency. Radiotherapy to the central nervous system should not be given concurrently with intrathecal Methotrexate. SIDE EFFECTS WITH METHOTREXATE The most frequently reported adverse reactions include ulcerative stomatitis, leukopenia, nausea, and abdominal distress. Other frequently reported adverse effects are malaise, undue fatigue, chills and fever, dizziness and decreased resistance to infection. Other adverse reactions that have been reported with Methotrexate are listed below by organ system. In the oncology setting, concomitant treatment and the underlying disease make specific attribution of a reaction to Methotrexate difficult. BACKGROUND OF THE INVENTION Methotrexate based medicaments have been known in the art for years, and have been shown to possess anti-neoplastic, anti-angiogenic, anti-fibroblastic, and/or immunosuppressive activities. While administering methotrexate based medicaments have been identified as a promising remedy to treat many of the above-identified irregularities, delivering methotrexate based medicaments to an affected area of a living subject has remained heretofore largely problematic. Indeed, known prior art methods of administering methotrexate based medicaments, identified hereinbelow, 4 are replete with substantial drawbacks and/or life threatening complications. For example, delivering methotrexate based medicaments to an affected, local area of a living subject using a systemic delivery method is problematic because of the many severe, sometimes life threatening, side effects associated with systemic delivery of methotrexate based medicaments, such as, for examples, hepatitis, liver fibrosis, cirrhosis, leukopenia (bone marrow suppression), mucositis, ulcerative stomatitis, skin rash, nausea, abdominal distress, malaise, fatigue, chills and fever, diarrhea, gastrointestinal ulceration or perforation, pancreatitis, pericarditis, hypotension, deep venous thrombosis, thrombophlebitis, interstitial pneumonitis, headaches, drowsiness, cognitive dysfunction, reduced immunity, rash, photosensitivity, nephropathy, hematuria, alopecia, defective oogenesis, oligospermia, infertility, miscarriage, and birth defects. US Application 20050208137 provides compositions comprising an anti-angiogenic factor, and a polymeric carrier. Representative examples of anti-angiogenic factors include Anti-Invasive Factor, Methotrexate, Retinoic acids and derivatives thereof, and taxol. Also provided are methods for embolizing blood vessels, and eliminating biliary, urethral, esophageal, and tracheal/bronchial obstructions. This formulation is not suitable for topical applications. United States Application 20050153969 shows a method for treating neoplastic, angiogenic, fibroblastic, and/or immunosuppressive ocular irregularities of a living subject, comprising the steps of: providing a living subject, wherein the living subject includes an affected ocular area having a neoplastic, angiogenic, fibroblastic, and/or immunosuppressive irregularity; providing a methotrexate based medicament, wherein the methotrexate based medicament is capable of inhibiting DNA synthesis; associating a therapeutically effective concentration of the methotrexate based medicament with the affected ocular area of the living subject; and decreasing the neoplastic, angiogenic, fibroblastic, and/or 5 immunosuppressive ocular irregularity of the living subject. This formulation does not suggest Methotrexate topical application. United States Patent 6485740 discloses a methotrexate-containing transdermal preparation effective for rheumatoid arthritis comprises an organic amine. The organic amine may preferably be an alkonolamine such as monoethanolamine, diethanolamine, triethanolamine or diisopropanolamine, or an alkylamine such as ethylamine, diethylamine or triethylamine. The transdermal preparation is, for example, a plaster, a cataplasm, an ointment, a cream or a lotion. The base of this product is non aqueous but an oil based formulation containing an organic amine. OBJECT OF THE INVENTION The object of the invention is to provide an aqueous formulation composition of Methotrexate for topical application. Another object of the invention is to provide a formulation composition containing an aqueous based Methotrexate in a topical gel form for external use particularly for the treatment of skin cancer and psoriasis vulgaris. Yet another object of the invention is to provide a process for the preparation of a formulation composition containing Methotrexate in a topical gel form. SUMMARY OF THE INVENTION According to this invention, therefore there is provided a Methotrexate topical semisolid dosage form (gel) comprising a) therapeutically effective amounts of Methotrexate; b) at least one gel forming agent (polymer) having mass of about 0.5 % to 25 % of the total mass of the gel; c) at least one penetration enhancing agent having mass of about 25 % to about 60 % of the total mass of the gel; 6 d) at least one preservative and/or antioxidant having mass of about 0.001 % to about 2.0 % of the total mass of the gel; e) at least one fragrance (optional) having mass of about 0.01 % to about 1.0 % of the total mass of the gel; f) at least one surfactant having mass of about 0.1 % to about 3.0 % of the total mass of the gel; other pharmaceutical acceptable inert excipients such as solvents and pH adjusting agents to adjust the pH between 6.8 and 7.4. Typically, the quantity of Methotrexate ranges from about 0.1 %w/w to 1.5 %w/w. Typically, the mass of the gel forming agent (polymers) ranges from about 0.5 % to about 25 %of the total mass of the gel and preferably from about 1 % to about 11 % of the total mass of the gel. Typically, the mass of the penetration enhancing agents ranges from about 25 % to about 60 % of the total mass of the gel and preferably, from about 35 % to about 50 % of the total mass of the gel. Typically, the mass of the preservatives and/or antioxidants ranges from about 0.001 % to about 2.0 % of the total mass of the gel and preferably, from about 0.05 % to about 1 % of the total mass of the gel. In accordance with one embodiment of the invention, the preservative is of at least one compound selected from a group of compounds consisting of chlorocresol, methyl paraben, propyl paraben, thiomarsal, sorbic acid, and potassium sorbate and benzyl alcohol. Typically, the preservative is in the range of 0.001 % to 2.0 % of the total mass of the gel. In accordance with yet another embodiment of the invention, the antioxidants is of at least one compound selected from a group of compounds consisting of Butylated hydroxy anisole (BHA), Butylated 7 hydroxy toluene (BHT), sodium metabisulfite, sodium sulfite, sodium bisulfite and propyl gallate. Typically, the antioxidant is in the range of 0.001 % to 2.0 % of the total mass of the gel. In accordance with yet another embodiment of the invention, the surfactant is of at least one compound selected from a group of compounds consisting of polysorbate 80, polysorbate 20, sorbitan groups (spans). Typically, the surfactant is in the range of 0. 1 % to 3.0 % of the total mass of the gel. In accordance with yet another embodiment of the invention, the pH adjusting agents is of at least one compound selected from a group of compounds consisting of diethanolamine, triethanolamine, sodium hydroxide, hydrochloric acid, citric acid and mono basic sodium phosphate. In accordance with yet another embodiment of the invention, the solvent is of at least one compound selected from a group of compounds consisting of isopropyl alcohol and purified water. In accordance with yet another embodiment of the invention, the penetration enhancing agent is of at least one compound selected from a group of compounds consisting of Propylene glycol, polyethylene glycols [PEG-300, PEG-400, etc], and other substituted glycols such as different grade of cremaphors, to increase the drug penetration in the skin. Typically, the penetration enhancing agent is in the range of 25 % to 60 % of the total mass of the gel. In accordance with yet another embodiment of the invention, the viscosity increasing (gel forming) agents is of at least one compound selected from a group of compounds consisting of carbomors [cross linked polymers of acrylic acid], cellulosic polymers such as hydroxypropyl methylcellulose, methylcellulose, sodium carboxy methylcellulose, hydroxypropyl cellulose, carbopol 910, carbopol 934P, carbopol 940, carbopol 941, and carbopol 1342. 8 Typically, the viscosity increasing (gel forming) agents is in the range of 0.5 % to 25 % of the total mass of the gel. In accordance with another aspect of the invention, there is provided a process for preparing the topical semisolid dosage form (gel) comprising the steps of a) Preparing a mixture of penetration enhancing agent solvent and a purified water in a container to obtain a solvent mixture; b) Dispersing a viscosity increasing (gel forming) agent in the solvent mixture in a container to obtain a concentrated dispersion; c) Dissolving sodium hydroxide in purified water to obtain a solution of sodium hydroxide; d) Dissolving dispenced quantity of Methotrexate in the solution of sodium hydroxide to obtain a Methotrexate solution; e) Adding the Methotrexate solution, solvent mixture, surfactant, solvent to a mixing tank with stirring; f) Adding the dispersion obtained in step b to the mixing tank and stirring slowly to homogenize the dispersion to obtain a homogenized dispersion; g) Adjusting the pH of the homogenized dispersion between 6.8 and 7.4 and the volume with purified water to obtain the gel. DETAILED DESCRIPTION OF THE INVENTION The main feature of this invention is the preparation of the topical semisolid dosage form (gel) of the formulation comprising Methotrexate. The method for treating a patient comprises topically applying the pharmaceutical formulation comprising a combination of (a)0.1 %w/w to 1.5 %w/w of Methotrexate. (b)0.5 %w/w to 25 %w/w of gel forming agent (polymers) (c) 25 %w/w to 60 %w/w of penetration enhancing agents. (d)0.001 %w/w to 2.0 %w/w of preservatives and/or antioxidants. (e)0.01 %w/w to 1.0 % w/w of fragrance (Optional) 9 (f) other pharmaceutical acceptable inert excipients such as solvents and pH adjusting agents The said formulation may contain one or more pharmaceutical acceptable inert excipients comprising of preservatives, antioxidants, surfactants and pH adjusting agents. The preservative in the formulation is essential as the viscosity enhancer polymer it self act as a suitable medium for the microbial growth. However the use of the glycol solvents in high concentration in the formulation reduce the occurrence of such microbial growth. Additional support to prevent this microbial growth may be achieved by the use of other preservatives such as chlorocresol, methyl paraben, propyl paraben, thiomarsal, sorbic acid, and potassium sorbate and benzyl alcohol. The preferable concentration of these preservatives may be 0.001 %w/w to 2 %w/w. The antioxidants are optionally used in the formulation may includes Butylated hydroxy anisole (BHA), Butylated hydroxy toluene (BHT), sodium metabisulfite, sodium sulfite, sodium bisulfite and propyl gallate. The surfactants used in the formulation mainly to improve the penetration of the active ingredients to the skin by increasing the solublization of the active in the lipophilic membrane. These may include polysorbate 80, polysorbate 20, sorbitan groups (spans). The concentration of surfactant in the formulation may include 0.1 %w/w to 3.0 % w/w. The pH adjusting agents used in the formulation may includes diethanolamine, triethanolamine, sodium hydroxide, hydrochloric acid, citric acid and mono basic sodium phosphate. Semisolid base in the formulation mainly comprising of the adjuvant solvents, viscosity enhancer (jelling) agents and solvent such as isopropyl alcohol and purified water. The adjuvant solvent in the formulation includes glycols that may be selected from the Propylene glycol, polyethylene glycols [PEG-300, PEG- 10 400, etc], and other substituted glycols such as different grade of cremaphors. The viscosity increasing agents may include the synthetic polymers such as carbomors [cross linked polymers of acrylic acid], cellulosic polymers such as hydroxypropyl methylcellulose, methylcellulose, sodium carboxy methylcellulose, and hydroxypropyl cellulose. The different grades of the cabomers available for the topical gel formulation, those are carbopol 910, carbopol 934P, carbopol 940, carbopol 941, and carbopol 1342. These are used in concentration of 0.5 %w/w to 2.0 %w/w for the purpose. When cellulosic polymers used in the formulation high concentrations is preferred [3 %w/w to 15 %w/w for the same purpose. The brief method of manufacturing the said formulation includes the following steps. a) Preparing a mixture of penetration enhancing agent solvent and a purified water in a container to obtain a solvent mixture; b) Dispersing a viscosity increasing (gel forming) agent in the solvent mixture in a container to obtain a concentrated dispersion; c) Dissolving sodium hydroxide in purified water to obtain a solution of sodium hydroxide; d) Dissolving dispenced quantity of Methotrexate in the solution of sodium hydroxide to obtain a Methotrexate solution; e) Adding the Methotrexate solution, solvent mixture, surfactant, solvent to a mixing tank with stirring; f) Adding the dispersion obtained in step b to the mixing tank and stirring slowly to homogenize the dispersion to obtain a homogenized dispersion; g) Adjusting the pH of the homogenized dispersion between 6.8 and 7.4 and the volume with purified water to obtain the gel. 11 EXAMPLES Following are few examples sited in accordance to the said formulation. But it is not intended that the scope of this invention is limited to these. EXAMPLE - 1: Each gram of the gel contains Methotrexate 0.25 %w/w Gel base q.s. MANUFACTURING PROCESS [Batch size: 100 kg] Step-I Transfer 35 kgs Propylene Glycol and 18 lits. distilled water to the steam jacketed planetary mixer. Add 1.5 kgs Carbopol slowly under fast stirring. Dissolve Carbopol completely. Step-II Take 5.0 lits of distilled water in a separate glass beaker and then add 250 Gms of Methotrexate with slow mixing. Add sufficient quantity of sodium hydroxide 10 % solution to the beaker so as to form a clear solution. Then add 5.0 kg of the propylene glycol, 1 kg of benzyl alcohol, 0.5 kg of polysorbate 80 to this solution one after another with constant stirring. Step-III Transfer the solution obtained in step II to step I solution slowly under fast stirring. Step-IV Add the remaining 10 kg of propylene glycol to the mixer. Adjust the final weight preparation up to 100 kgs with distilled water. 12 StepV In Process 1. Appearance: Clear, yellow color transparent gel. 2. pH : 6.45 EXAMPLE- 2: Each gram of the gel contains Methotrexate 0.25 % w/w Gel Base q.s. MANUFACTURING PROCESS [Batch size: 100 kg] Step-I Transfer 30 kgs Propylene Glycol and 18 lits. distilled water to the steam jacketed Planetary mixer. Add 1.2 kgs Carbopol slowly under fast stirring. Dissolve Carbopol completely. Step-II Take 5.0 lits of distilled water in a separate glass beaker and then add 250 Gms of Methotrexate with slow mixing. Add sufficient quantity of sodium hydroxide 10 % solution to the beaker so as to form a clear solution. Then add 5.0 kg of the propylene glycol, 1 kg of benzyl alcohol, 0.5 kg of cremaphor RS-40 to this solution one after another with constant stirring. Step-III Transfer the solution obtained in step II to step I solution slowly under fast stirring. 13 Step-IV Add the 10 kg of polyethylene glycol 400 to the mixer. Adjust the final weight preparation up to 100 kgs with distilled water. StepV In Process 1. Appearance: Clear, yellow color transparent gel. 2. pH : 6.50 EXAMPLE- 3: Each gram of the gel contains Methotrexate 0.25 % w/w Gel Base q.s. MANUFACTURING PROCESS [Batch size: 100 kg] Step-I Transfer 25 kgs Propylene Glycol and 25 lits. distilled water to 100 lits. capacity steam jacketed Planetary mixer. Add 10 kgs hydroxypropyl methylcellulose slowly under fast stirring. Dissolve the polymer completely. Step-II Take 5.0 lits of distilled water in a separate glass beaker and then add 250 Gms of Methotrexate with slow mixing. Add sufficient quantity of sodium hydroxide 10 % solution to the beaker so as to form a clear solution. Then add 5.0 kg of the propylene glycol, 1 kg of benzyl alcohol, 0.5 kg of polysorbate 80 to this solution one after another with constant stirring. 14 Step-Ill Transfer the solution obtained in step II to step I solution slowly under fast stirring. Step-IV Add the remaining 10 kg of propylene glycol to the mixer. Adjust the final weight preparation up to 100 kgs with distilled water. Step V In Process 1. Appearance: Clear, yellow color transparent gel. 2. pH : 6.8 EXAMPLE - 4: Each gram of the gel contains Methotrexate 0.25 % w/w Gel Base q.s. MANUFACTURING PROCESS [Batch size: 100 kg] Step-I Transfer 30 kgs Propylene Glycol and 25 lits. distilled water to 100 lits. capacity steam jacketed Planetary mixer. Add 8 kgs hydroxypropyl methylcellulose and 4.0 kg of sodium carboxy methylcellulose slowly under fast stirring. Dissolve the polymer completely. Step-II Take 5.0 lits of distilled water in a separate glass beaker and then add 250 Gms of Methotrexate with slow mixing. Add sufficient quantity of sodium 15 hydroxide 10 % solution to the beaker so as to form a clear solution. Then add 5.0 kg of the propylene glycol, 1 kg of benzyl alcohol, 0.5 kg of polysorbate 40 to this solution one after another with constant stirring. Step-Ill Transfer the solution obtained in step II to step I solution slowly under fast stirring. Step-IV Add the remaining 10 kg of polyethylene glycol 400 to the mixer. Adjust the final weight preparation up to 100 kgs with distilled water. Step V In Process 1. Appearance: Clear, yellow color transparent gel. 2. pH : 7.2 EXAMPLE - 5 (STABILITY STUDY) The three batches of each formulations of above examples are placed in the stability chamber for stability study. The result promise that these formulations are stable in room temperature (bellow 25 °C) for at least 18 months with a maximum decrease of the potency up to 8 % than the initial concentration. On exposure to the higher temperature (more than 40 °C) the product gets degraded. It has also studied that the product is sensitive to light to some extent. EXAMPLE - 6 (MEDICAL TRIAL) For medical trial a group of total 20 numbers of adult patients diagnosed clinically as plaque type of palmoplantar psoriasis (>20% of the palm 16 and/or sole areas involved) were included in the study. The age groups of these patients are in between 21 to 74 years. Topical Methotrexate 0.25% gel was applied twice daily to the lesions for twelve weeks. The drug was well tolerated by all patients. Methotrexate 0.25% gel effectively controls psoriasis in the 75 % cases; remaining patients show improvement in the infection after thrice daily applications for 8 week of treatment. These study suggested that the topical gel of this present invention formulation is an effective alternative to the oral or perenteral therapy for skin cancers and psoriasis. Secondly there is a need for this as it was studied that in the systemic therapy of Methotrexate shows many severe side effects which otherwise avoided by direct applications. _ _ _ / / / / / / / / / / / / 17 I Claim: 1. The.present invention-relates to Methotrexate topical semisolid dosage form(gel) comprising a) therapeutically effective amounts of Methotrexate; b) at least one gel forming agent (polymer) having mass of about 0.5 % to 25 % of the total mass of the gel; c) at least one penetration enhancing agent having mass of about 25 % \p about 60 % of the total mass of the gel; d) at least one\ preservative and/or antioxidant having mass of about\0.001 % to about 2.0 % of the total mass of the gel; e) at least one frabrance (optional) having mass of about 0.01 % to about a.O % of the total mass of the gel; f) at least one surfactant having mass of about 0.1 % to about 3.0 % of the\total mass of the gel; g) other pharmaceutical acceptable inert excipients such as solvents and pH adjusting agents to adjust the pH between 6.8 and 7.4. 2. A topical semisolid dosage form (gel) as claimed in claim 1, wherein the quantity of Methotrexate ranges from about 0.1 %w/w to 1.5 %w/w. 3. A topical semisolid dosage form (gel) as claimed in claim 1 or claim 2, wherein the mass of the gel forming (viscosity increasing) agent ranges from about 0.5 % to about 25 % of the total Vnass of the gel. 4. A topical semisolid dosage form (gel) as Claimed in claim 1 or claim 2, wherein the mass of the penetration enhancing agent ranges from about 25 % to about 60 % of the total mass of the gel. 5. A topical semisolid dosage form (gel) as claimed in claim 1 or claim 2, wherein the mass of the preservative ranges from about 3 % to about 6 % of the total mass of the gel. \ / 18 I Claim: 1. A Methotrexate topical semisolid dosage form (gel) comprising a) therapeutically effective amounts of Methotrexate; b) at least one gel forming agent (polymer) having mass of about 0.5 % to 25 % of the total mass of the gel; c) at least one penetration enhancing agent having mass of about 25 % to about 60 % of the total mass of the gel; d) at least one preservative and/or antioxidant having mass of about 0.001 % to about 2.0 % of the total mass of the gel; e) at least one fragrance (optional) having mass of about 0.01 % to about 1.0 % of the total mass of the gel; f) at least one surfactant having mass of about 0.1 % to about 3.0 % of the total mass of the gel; g) other pharmaceutical acceptable inert excipients such as solvents and pH adjusting agents to adjust the pH between 6.8 and 7.4. 2. A topical semisolid dosage form (gel) as claimed in claim 1, wherein the quantity of Methotrexate ranges from about 0.1 %w/w to 1.5 %w/w. 3. A topical semisolid dosage form (gel) as claimed in claim 1 or claim 2, wherein the mass of the gel forming (viscosity increasing) agent ranges from about 0.5 % to about 25 % of the total mass of the gel. 4. A topical semisolid dosage form (gel) as claimed in claim 1 or claim 2, wherein the mass of the penetration enhancing agent ranges from about 25 % to about 60 % of the total mass of the gel. 5. A topical semisolid dosage form (gel) as claimed in claim 1 or claim 2, wherein the mass of the preservative ranges from about 3 % to about 6 % of the total mass of the gel. 18 6. A topical semisolid dosage form (gel) as claimed in claim 1 or claim 2, wherein the mass of the antioxidant ranges from about 0.001 % to about 2.0 % of the total mass of the gel. 7. A topical semisolid dosage form (gel) as claimed in claim 1 or claim 2, wherein the mass of the surfactant ranges from about 0.1 % to about 3.0 % of the total mass of the gel. 8. A topical semisolid dosage form (gel) as claimed in claim 1 or claim 2, wherein the mass of the solvent ranges from about 5.0 % to about 65 % of the total mass of the gel. 9. A topical semisolid dosage form (gel) as claimed in any one of the preceding claims, wherein the preservative is of at least one compound selected from a group of compounds consisting of chlorocresol, methyl paraben, propyl paraben, thiomarsal, sorbic acid, and potassium sorbate and benzyl alcohol. 10. A topical semisolid dosage form (gel) as claimed in any one of the preceding claims, wherein the antioxidant is of at least one compound selected from a group of compounds consisting of Butylated hydroxy anisole (BHA), Butylated hydroxy toluene (BHT), sodium metabisulfite, sodium sulfite, sodium bisulfite and propyl gallate. 11. A topical semisolid dosage form (gel) as claimed in any one of the preceding claims, wherein the surfactant is of at least one compound selected from a group of compounds consisting of polysorbate 80, polysorbate 20, sorbitan groups (spans). 12. A topical semisolid dosage form (gel) as claimed in any one of the preceding claims, the pH adjusting agent is of at least one compound selected from a group of compounds consisting of diethanolamine, triethanolamine, sodium hydroxide, hydrochloric acid, citric acid and mono basic sodium phosphate. 13. A topical semisolid dosage form (gel) as claimed in any one of the preceding claims, wherein the solvent is of at least one compound selected 19 from a group of compounds consisting of isopropyl alcohol and purified water. 14. A topical semisolid dosage form (gel) as claimed any one of the preceding claims, wherein the penetration enhancing agent is of at least one compound selected from a group of compounds consisting of Propylene glycol, polyethylene glycols [PEG-300, PEG-400, etc], and other substituted glycols such as different grade of cremaphors. 15. A topical semisolid dosage form (gel) as claimed any one of the preceding claims, wherein the viscosity increasing (gel forming) agent is of at least one compound selected from a group of compounds consisting of carbomors [cross linked polymers of acrylic acid], cellulosic polymers such as hydroxypropyl methylcellulose, methylcellulose, sodium carboxy methylcellulose, hydroxypropyl cellulose, carbopol 910, carbopol 934P, carbopol 940, carbopol 941, and carbopol 1342. 16. A process for preparing a topical semisolid dosage form (gel) as claimed in any one of the preceding claims comprising the steps of a) Preparing a mixture of penetration enhancing agent solvent and a purified water in a container to obtain a solvent mixture; b) Dispersing a viscosity increasing (gel forming) agent in the solvent mixture in a container to obtain a concentrated dispersion; c) Dissolving sodium hydroxide in purified water to obtain a solution of sodium hydroxide; d) Dissolving dispenced quantity of Methotrexate in the solution of sodium hydroxide to obtain a Methotrexate solution; e) Adding the Methotrexate solution, solvent mixture, surfactant, solvent to a mixing tank with stirring; f) Adding the dispersion obtained in step b to the mixing tank and stirring slowly to homogenize the dispersion to obtain a homogenized dispersion; g) Adjusting the pH of the homogenized dispersion between 6.8 and 7.4 and the volume with purified water to obtain the gel. 20

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