Title of Invention

A DISPERSIBLE TABLET SKELETAL MUSCLE RELAXANT AND NSAID AND METHOD OFMAKING THE SAME

Abstract

A synergistic antispasmodic, analgesic formulation comprising a dispersible tablet consisting of (a) 500 mg to 1000 mg of methocarbamol; (b) 50 to 200 mg of nimesulide; and (c) pharmaceutically acceptable inert excipients consisting of at least one diluent from 5 % to 45 % of the total mass of the formulation, at least one binder from 0.1% to 4% of the total mass of the formulation, at least one glidant from 0.01% to 3% of the total mass of the formulation , at least one lubricant from 0.6% to 5% of the total mass of the formulation, at least one sweetening agent from 0.5% to 5% of the total mass of the formulation, at least one flavoring agent from 0.5% to 5% of the total mass of the formulation and at least one disintegrant from 0.6% to 8% of the total mass of the formulation, and optionally at least one surfactant from 0.01 to 5% of the total mass of the formulation.

Full Text

FORM - 2 THE PATENTS ACT, 1970 (39 of 1970) THE PATENTS RULES, 2003 COMPLETE (See section 10 and rule 13) A SYNERGISTIC ANTISPASMODIC, ANALGESIC FORMULATION AND A METHOD OF MAKING THE SAME SANJEEV KHANDELWAL, an Indian National of Prem Nivas, 13, Altamount Road, Mumbai 400 026, Maharashtra, India 4 APR 2006 GRANTED THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED:- 11-9-2006 FIELD OF INVENTION This invention relates to a synergistic formulation comprising in combination a skeletal muscle relaxant and an analgesic and to a method of making the same. WHAT THE INVENTION ENVISAGES This invention envisages a synergistic formulation composition containing methocarbamol and nimesulide in a dispersible tablet form. The fixed dose combination of methocarbamol and nimesulide produces a synergistic response in the effective relief of pain. In particular this invention envisages a dispersible tablet formulation for oral administration of methocarbamol and nimesulide. Methocarbamol is centrally acting skeletal muscle relaxant useful in painful musculoskeletal conditions associated with spasm. Nimesulide is a selective COX - II inhibitor with analgesic, antipyretic and anti-inflammatory actions. It has less G.I side effects and is safe option in asthmatic patients too... The said formulation is particularly indicated for prolapsed intervertebratral disc, low back pain, cervical spondylitis and accidental traumas. The said formulation has no side effects such as drowsiness, allergies, dyspepsia, and rash. Therapeutic effective amount of methocarbamol used in the formulation is preferably as pure methocarbamol or any pharmaceutical^ acceptable form such as methocarbamol (micronised) or any other stereochemical pure form of it. Therapeutic effective amount of nimesulide used in the formulation is preferably nimesulide in its pure form or any pharmaceutically acceptable form. The two active materials in the formulation can be formulated within a dosage form wherein the two active materials are mixed along with excipients to form a uniform blend and thereafter bound with suitable binder to form granules of the mixed active blend which when compressed in a tablet form has a disintegration time of not more than three minutes. DETAILED DESCRIPTION OF THE INVENTION The main feature of this invention is the use of both active ingredients for making the oral dosage form of the formulation methocarbamol and nimesulide in a single dispersible tablet dosage form. The method for treating a patient comprises orally administering a pharmaceutical formulation comprising a combination of (a) 500 mg to 1000 mg of methocarbamol which is called the first active ingredient (b) 50 mg to 200 mg of nimesulide which is called the second active ingredient, (c) pharmaceutically acceptable inert excipients (d) a pharmaceutically acceptable carrier. According to this invention, a synergistic antispasmodic, analgesic formulation comprising a dispersible tablet consisting of (a) 500 mg to 1000 mg of methocarbamol;(b) 50 to 200 mg of nimesulide; and (c) pharmaceutically acceptable inert excipients consisting of at least one diluent from 5 % to 45 % of the total mass of the formulation, at least one binder from 0.1% to 4% of the total mass of the formulation, at least one glidant from 0.01 % to 3% of the total mass of the formulation, at least one lubricant from 0.6% to 5% of the total mass of the formulation, at least one sweetening agent from 0.5% to 5% of the total mass of the formulation, at least one flavoring agent from 0.5% to 5% of the total mass of the formulation and at least one disintegrant from 0.6% to 8% of the total mass of the formulation is provided . In accordance with a preferred aspect of the invention, the formulation includes a surfactant being from 0.01% to 5% of the total mass of the formulation. The diluent may be any pharmaceutically acceptable inert material selected from the group consisting of micorcrystalline cellulose, starches, lactose, mannitol, calcium phosphate, dibasic calcium phosphate and mixtures of these. The disintegrating agent in the formulation which will accelerate the dispersion of the active particles is at least one compound selected from a group of compounds consisting of Ac-di-sol, sodium lauryl sulphate,cross-linked polyvinylpyrrolidone, carboxymethyl starch, natural starch, microcrystalline cellulose, cellulose gum and mixtures of these. The binders in the formulation increases the bulk density of the active particles and make it easier to formulate in a compressed form. It is at least one compound selected from a group of compounds consisting of pregelatinized starch, starches, gelatin, vinyl chloride, povidone, hydroxypropyl cellulose, ethyl cellulose, cellulose acetate phthalate, hydroxypropylmethyl cellulose and mixture of these. The formulation may also contain preservatives so as to prevent the growth of microorganisms. The preservative mainly includes the benzoic acid esters such as methyl paraben, propyl paraben, sodium benzoate, benzyl alcohol. The formulation may optionally includes one surfactant selected from the group consisting of: sodium lauryl sulfate, sodium carboxy methyl cellulose, calcium carboxy methyl cellulose, hydrogenated or non-hydrogenated glycerolipids, ethoxylated or non-ethoxylated, linear or branched, saturated or mono- or polyunsaturated C6 to C3o fatty acids in the form of the acid or an alkali metal or its salt, cyclodextrin, sodium lauryl sulfate, alkaline earth metal or amine salt, ethoxylated or non-ethoxylated esters of sucrose, sorbitol, sorbitan monooleate, mannitol, glycerol or polyglycerol containing from 2 to 20 glycerol units, or glycol with said fattyacids, mono-, di- or triglycerides or mixtures of glycerides of said fatty acids, ethoxylated or non-ethoxlylated, linear or branched, saturated or mono- or polyunsaturated (C6 to C30 fatty alcohols, cholesterol and derivatives thereof, other derivatives with a sterol skeleton, ethoxylated or non-ethoxylated ethers of sucrose, sorbitol, mannitol, glycerol or polyglycerol containing from 2 to 20 glycerol units, or glycol with said fatty alcohols, hydrogenated or non-hydrogenated, polyethoxylated vegetable oils, polyoxyethylene/ polyoxypropylene block polymers (poloxamers), polyethylene glycol hydroxystearate, sphingolipids and sphingosine derivatives, polyalkyl glucosides, ceramides, polyethylene glycol/alkyl glycol copolymers, and polyethylene glycol/polyalkylene glycol ether di-block or tri-block copolymers, diacetylated monoglycerides, diethylene glycol monostearate, ethylene glycol monostearate, glyceryl monooleate, glyceryl monostearate, propylene glycol monostearate, macrogol esters, macrogol stearate 400, macrogol stearate 2000, polyoxyethylene 50 stearate, macrogol ethers, cetomacrogol 1000, lauromacrogols, nonoxinols, octoxinols, tyloxapol, poloxamers, polyvinyl alcohols, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80, polysorbate 85, sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, sorbitan tristearate and sucrose esters. The glidants in the formulation accelerate the flow of the granules at the time of tabletting or filling is at least one compound selected from a group of compounds consisting of corn starch, talcum, colloidal silicon dioxide, silicon dioxide and mixtures of these. The formulation includes a lubricant, which reduces adhesion and ease release of the product, is at least one compound selected from a group of compounds includes magnesium stearate, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, surfactants, talc, waxes and zinc stearate. The formulation may also include at least one sweetener such as aspartame, sucrose, xylitol, mannitol, maltodextrine, betacyclodextrine, stevia and as like and at least one flavor that may be approved synthetic flavors such as strawberry, vanilla, mixed fruit flavor etc or it may also contain natural flavors to mask the bitter taste of the active ingredients. According to one aspect of this invention there is provided a process for making a synergistic Skeletal Muscle Relaxant and NSAID formulation comprising the steps of [a] dissolving a dispensed quantity of preservatives and binder in a solvent one after one in a S.S. Container to form a binder solution; [b] transferring dispensed quantities of milled and/or sifted methocarbamol and nimesulide either in combined or separately with diluents in a planetary mixer with variable speed ranges from 12 to 40 rpm and mixing the active ingredients and diluents for 15 to 30 minutes at an ambient temperature below 25 degrees Celsius and relative humidity below 60% to obtain a first uniform mass; [c] transferring the binder solution slowly to the contents of planetary mixer and rotating the planetary mixer at slow speed for 10 to 20 minutes till a first uniform dough is formed; [d] passing the first dough to a multimill fitted with sieves of diameter ranging from 10 mm to 14 mm at medium speed to produce wet granules; [e] transferring the wet granules to a drier for drying at 50° C to 55° C; [f] passing the dried granules to 16-mesh sieve through vibrosifter and pass retained granules through multimill using 1.5mm screen at a speed of 10 to 20 rpm to obtain dried uniformly sized granules; [g] lubricating the granules by passing the uniformly sized dried granules of the active ingredients to a double cone blender together with dispensed quantities of sifted lubricants, flavors, sweeteners, glidants, and disintegrating agents and mixing for 10 to 20 minutes to obtain lubricated granules; and [hj compressing the lubricated granules at a compression pressure of 3 to 10 kg/sq cm . at temperatures between 20°C to 30°C and relative Humidity: Below 60% to form cores. EXAMPLE -1 Each tablet contains: Methocarbamol 500 mg Nimesulide 100 mg MANUFACTURING PROCESS (Batch Size 1 Lakh Tablet) Step -1: Manufacturing of the granules 50 kg of Methocarbamol, 10 kg of Nimesulide, 5.0 kg of microcrystalline cellulose, 3.4 kg of starch were passed through a 40-mesh sieve and placed in a planetary mixer. The ambient temperature was maintained below 25 degrees Celsius and the relative humidity below 60%. The mixer was run for 25 minutes at 30 r.p.m. so that a homogenous mixture of the particles of active ingredients and the above said inert excipients resulted. 0.60 kg of starch mixed with 5 Kg of purified water in a stainless steel [s.s.] tank under continuous stirring to obtain slurry. Simultaneously heat 10 kgs of purified water in a jacketed steam vessel till boiling. Add 4gms of methyl paraben and dissolve it with stirring. Add the above said slurry to this boiling purified water until the binder was completely dissolved in the solvent. The solution was then added to the planetary mixer containing the homogenous mixture of the particles of active molecules with the excipients. Wet mixing was then commenced for 20 minutes at 15 r.p.m. to obtain a wet homogenous mixture mass. The wet homogenous mixture mass was milled, in a multimill fitted with 12 mm perforated sieve to obtain granules of mesh size 8 to 12 mm. The wet granules were subjected to drying: The granules were subjected to heated drying at a temperature of 50 to 60 degrees Celsius in a tray drier for 6 hrs. The drying mass was raked during the process. The Loss on drying was 1.2%. The dry granules were sifted in an 18-mesh vibrosifter to obtain uniform sized granules. Step - 2: Lubrication Through a vibrosifter of mesh size 40 meshes the following materials were passed individually and separately: 2.5 kg cross carmellose sodium, 0.8 kg of colloidal silicon dioxide, 0.3 kg of microcrystalline cellulose ,1.2 kg of talcum, and 1.2 kg of magnesium stearate. This sifted mass (except magnesium stearate) along with 0.5kg aspartame , 0.5 kg mixed fruit flavor and the dried granules were transferred to a double cone blender at temperature of 22 degrees Celsius and the mass was blended at speed of 30 r.p.m. for 25 minutes. 1.2 kg of magnesium stearate; was then added to the blender and further blending was done for 5 minutes resulting in the lubricated dispersible tabletmass. Step - 3 : Compression This dispersible tabletmass was fed to hopper of a single rotary compression machine and the compression pressure was set at 7 kg/sq cm. 1,00,000 Cores were obtained: Dimension: capsule shape, Standard curvature, with dimension 19.0 x 8.0 mm +/- 0.1 mm Avg weight of dispersible tablet760 mg ± 3 %. EXAMPLE - 2 Each tablet contains: Methocarbamol 500 mg Nimesulide 100 mg MANUFACTURING PROCESS (Batch Size 1 Lakh Tablet) Step -1: Manufacturing of the granules 50 Kg of methocarbamol, 10 kg of nimesulide, 5.0 kg of microcrystalline cellulose, 3.7 kg of starch were passed through a 40-mesh sieve and placed in a planetary mixer. The ambient temperature was maintained below 25 degrees Celsius and the relative humidity below 60%. The mixer was run for 25 minutes at 26 r.p.m. so that a homogenous mixture of the particles of active ingredients and the above said inert excipients resulted. Add 4gms of methyl paraben and 0.3 kg of polyvinyl pyrrolidone to 10 kg of purified water and stir until the binder was completely dissolved in the solvent. The solution was then added to the planetary mixer containing the homogenous mixture of the particles of active molecules with the excipients. Wet mixing was then commenced for 20 minutes at 15 r.p.m. to obtain a wet homogenous mixture mass. The wet homogenous mixture mass was milled, in a multimill fitted with 12 mm perforated sieve to obtain granules of mesh size 8 to 12 mm. The wet granules were subjected to drying: The granules were subjected to heated drying at a temperature of 50 to 60 degrees Celsius in a Fluidized bed drier for 2 hrs. The drying mass was raked during the process. The Loss on drying was 1.4%. The dry granules were sifted in an 18-mesh vibrosifter to obtain uniform sized granules. Step - 2: Lubrication Through a vibrosifter of mesh size 40 the following materials were passed individually and separately: 0.8 kg of colloidal silicon dioxide, 2.5 kg of cross carmellose sodium, 1.2 kg of talcum, and 1.2 kg of magnesium stearate. This sifted mass (except magnesium stearate) along with 0.5kg aspartame , 0.5kg mixed fruit flavor and the dried granules were transferred to a double cone blender at temperature of 22 degrees Celsius and the mass was blended at speed of 30 r.p.m. for 25 minutes. 1.2 kg of magnesium stearate; was then added to the blender and further blending was done for 5 minutes resulting in the lubricated dispersible tabletmass. Step - 3 : Compression This dispersible tabletmass was fed to hopper of a single rotary compression machine and the compression pressure was set at 7 kg/sq cm. 1,00,000 Cores were obtained: Dimension: capsule shape, Standard curvature, with dimension 19.0 x 8.0 mm +/- 0.1 mm Avg weight of dispersible tablet760 mg ± 3 %. EXAMPLE - 3 Each tablet contains: Methocarbamol 750 mg Nimesulide 100 mg MANUFACTURING PROCESS (Batch Size 1 Lakh Tablet) Step - 1: Manufacturing of the granules 75 Kg of methocarbamol, 10 kg of nimesulide, 6.0 kg of microcrystalline cellulose, and 3.5 kg of starch were passed through a 40-mesh sieve and placed in a planetary mixer. The ambient temperature was maintained below 25 degrees Celsius and the relative humidity below 60%. The mixer was run for 25 minutes at 26 r.p.m. so that a homogenous mixture of the particles of active ingredients and the above said inert excipients resulted. 0.5 kg of polyvinylpyrrolidone mixed with 5 Kg of purified water in a stainless steel [s.s.] tank under continuous stirring to obtain slurry. Simultaneously heat 10 kgs of purified water in a jacketed steam vessel till boiling. Add 5gms of methyl paraben and dissolve it with stirring. Add the above said slurry to this boiling purified water until the binder was completely dissolved in the solvent. The solution was then added to the planetary mixer containing the homogenous mixture of the particles of active molecules with the excipients. The wet homogenous mixture mass was milled, in a multimill fitted with 12 mm perforated sieve to obtain granules of mesh size 8 to 12 mm. The wet granules were subjected to drying: The granules were subjected to heated drying at a temperature of 50 to 60 degrees Celsius in a Fluidized bed drier for 2 hrs. The drying mass was raked during the process. The Loss on drying was 1.4%. The dry granules were sifted in an 18-mesh vibrosifter to obtain uniform sized granules. Step - 2: Lubrication Through a vibrosifter of mesh size 40 meshes the following materials were passed separately and individually,, 0.3 kg of microcrystalline cellulose, 4.0 kg of crosscarmellose sodium , 1.0 kg of colloidal silicon dioxide, 1.5 kg of talcum, and 1.2 kg of magnesium stearate. This sifted mass (except magnesium stearate) along with 0.5kg aspartame, 0.5kg mixed fruit flavor and the dried granules were transferred to a double cone blender at temperature of 22 degrees Celsius and the mass was blended at speed of 30 r.p.m. for 25 minutes. 1.2 kg of magnesium stearate; was then added to the blender and further blending was done for 5 minutes resulting in the lubricated dispersible tabletmass. Step - 3 : Compression This dispersible tabletmass was fed to hopper of a single rotary compression machine and the compression pressure was set at 6 kg/sq cm. 1,00,000 Cores were obtained: Dimension: capsule shape, Standard curvature, with dimension 21.0 x 9.0 mm +/- 0.1 mm Avg weight of dispersible tablet1040 mg ± 3 %. EXAMPLE - 4 Each tablet contains: Methocarbamol 750 mg Nimesulide 100 mg MANUFACTURING PROCESS (Batch Size 1 Lakh Tablet) Step -1: Manufacturing of the granules 75 Kg of methocarbamol, 10 kg of nimesulide, 6.0 kg of microcrystalline cellulose and 4.0 kg of starch were passed through a 40-mesh sieve and placed in a planetary mixer. The ambient temperature was maintained below 25 degrees Celsius and the relative humidity below 60%. The mixer was run for 25 minutes at 30 r.p.m. so that a homogenous mixture of the particles of active ingredients and the above said inert excipients resulted. 4.0 kg of starch mixed with 5 Kg of purified water in a stainless steel [s.s.] tank under continuous stirring to obtain slurry. Simultaneously heat 10 kgs of purified water in a jacketed steam vessel till boiling. Add 5gms of methyl paraben and dissolve it with stirring. Add the above said slurry to this boiling purified water until the binder was completely dissolved in the solvent. The solution was then added to the planetary mixer containing the homogenous mixture of the particles of active molecules with the excipients. Wet mixing was then commenced for 20 minutes at 15 r.p.m. to obtain a wet homogenous mixture mass. The wet homogenous mixture mass was milled, in a multimill fitted with 12 mm perforated sieve to obtain granules of mesh size 8 to 12 mm. The wet granules were subjected to drying: The granules were subjected to heated drying at a temperature of 50 to 60 degrees Celsius in a tray drier for 6 hrs. The drying mass was raked during the process. The Loss on drying was 1.3%. The dry granules were sifted in an 18-mesh vibrosifter to obtain uniform sized granules. Step - 2: Lubrication Through a vibrosifter of mesh size 40 meshes the following materials were passed individually and separately: 0.3 kg of microcrystalline cellulose ,4.0 kg of cross carmellose sodium, 1.0 kg of colloidal silicon dioxide, 1.5 kg of talcum, and 1.2 kg of magnesium - stearate. This sifted mass (except magnesium stearate) along with 0.5kg aspartame , 0.5kg mixed fruit flavor and the dried granules were transferred to a double cone blender at temperature of 22 degrees Celsius and the mass was blended at speed of 30 r.p.m. for 25 minutes. 1.2 kg of magnesium stearate; was then added to the blender and further blending was done for 5 minutes resulting in the lubricated dispersible tabletmass. Step -3: Compression This dispersible tabletmass was fed to hopper of a single rotary compression machine and the compression pressure was set at 5 kg/sq cm. 1,00,000 Cores were obtained: Dimension: capsule shape, Standard curvature, with dimension 21.0 x 9.0 mm +/- 0.1 mm Avg weight of dispersible tablet1040 mg ± 3 %. Trials were conducted by administering the tablets of the above examples to patients suffering from spasmodic pain. Patients were also administered nimesulide alone and separate tablets of nimesulide and methocarbamol. Significant results were obtained for the formulation of this invention over both nimesulide alone and the active ingredients administered separately. Unexpectedly, the relief was obtained significantly earlier [perceived to be at least 15 to 30 minutes earlier] but was more satisfactory [perceived to be at least 16.2% better]. In addition the single dosage form of the two active ingredients improved patient compliance as well as the cost of manufacture. I Claim: [1] A synergistic antispasmodic, analgesic formulation comprising a dispersible tablet consisting of (a) 500 mg to 1000 mg of methocarbamol; (b) 50 to 200 mg of nimesulide; and (c) pharmaceutically acceptable inert excipients consisting of at least one diluent from 5 % to 45 % of the total mass of the formulation, at least one binder from 0.1% to 4% of the total mass of the formulation, at least one glidant from 0.01% to 3% of the total mass of the formulation , at least one lubricant from 0.6% to 5% of the total mass of the formulation, at least one sweetening agent from 0.5% to 5% of the total mass of the formulation, at least one flavoring agent from 0.5% to 5% of the total mass of the formulation and at least one disintegrant from 0.6% to 8% of the total mass of the formulation, and optionally at least one surfactant from 0.01 to 5% of the total mass of the formulation. [2] A synergistic antispasmodic, analgesic formulation as claimed in claim 1, wherein the diluent is any pharmaceutically acceptable inert material selected from a group consisting of micorcrystalline cellulose, starches, lactose, mannitol, calcium phosphate, dibasic calcium phosphate and mixtures of these. [3] A synergistic antispasmodic, analgesic formulation as claimed in claim 1, wherein the disintegrating agent is at least one compound selected from a group of compounds consisting of Ac-di-sol, sodium lauryl sulphate,cross-linked polyvinylpyrrolidone, carboxymethyl starch, natural starch, microcrystalline cellulose, cellulose gum and mixtures of these. [4] A synergistic antispasmodic, analgesic formulation as claimed in claim 1, wherein the binders is at least one compound selected from a group of compounds consisting of pregelatinized starch, starches, gelatin, vinyl chloride, povidone, hydroxypropyl cellulose, ethyl cellulose, cellulose acetate phthalate, hydroxypropylmethyl cellulose and mixture of these. [5] A synergistic antispasmodic, analgesic formulation as claimed in claim 1, wherein the glidants is at least one compound selected from a group of compounds consisting of corn starch, talcum, colloidal silicon dioxide, silicon dioxide and mixtures of these. [6] A synergistic antispasmodic, analgesic formulation as claimed in claim 1, wherein the lubricant, is at least one compound selected from a group of compounds which includes magnesium stearate, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc, waxes and zinc stearate. [7] A synergistic antispasmodic, analgesic formulation as claimed in claim 1, wherein the sweetening agent is at least one compound selected from a group of compounds consisting of aspartame, sucrose, xylitol, mannitol, maltodextrine, betacyclodextrine, stevia together with at least one flavor that is approved synthetic or natural flavor such as strawberry, vanilla, mixed fruit flavor. [8] A synergistic antispasmodic, analgesic formulation as claimed in claim 1, wherein the surfactant is at least one compound selected from a group consisting of: sodium lauryl sulfate, sodium carboxy methyl cellulose, calcium carboxy methyl cellulose, hydrogenated or non-hydrogenated glycerolipids, ethoxylated or non-ethoxylated, linear or branched, saturated or mono- or polyunsaturated C6 to C30 fatty acids in the form of the acid or an alkali metal or its salt, cyclodextrin, sodium lauryl sulfate, alkaline earth metal or amine salt, ethoxylated or non-ethoxylated esters of sucrose, sorbitol, sorbitan monooleate, mannitol, glycerol or polyglycerol containing from 2 to 20 glycerol units, or glycol with said fattyacids, mono-, di- or triglycerides or mixtures of glycerides of said fatty acids, ethoxylated or non-ethoxlylated, linear or branched, saturated or mono- or polyunsaturated (C6 to C30 fatty alcohols, cholesterol and derivatives thereof, other derivatives with a sterol skeleton, ethoxylated or non-ethoxylated ethers of sucrose, sorbitol, mannitol, glycerol or poiyglycerol containing from 2 to 20 glycerol units, or glycol with said fatty alcohols, hydrogenated or non-hydrogenated, polyethoxylated vegetable oils, polyoxyethylene/ polyoxypropylene block polymers (poloxamers), polyethylene glycol hydroxystearate, sphingolipids and sphingosine derivatives, polyalkyl glucosides, ceramides, polyethylene glycol/alkyl glycol copolymers, and polyethylene glycol/polyalkylene glycol ether di-block or tri-block copolymers, diacetylated monoglycerides, diethylene glycol monostearate, ethylene glycol monostearate, glyceryl monooleate, glyceryl monostearate, propylene glycol monostearate, macrogol esters, macrogol stearate 400, macrogol stearate 2000, polyoxyethylene 50 stearate, macrogol ethers, cetomacrogol 1000, lauromacrogols, nonoxinols, octoxinols, tyloxapol, poloxamers, polyvinyl alcohols, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80, polysorbate 85, sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, sorbitan tristearate and sucrose esters. [9] A synergistic antispasmodic, analgesic formulation as claimed in claim 1, wherein the preservative is at least one compound selected from a group consisting of benzoic acid esters such as methyl paraben, propyl paraben, sodium benzoate, benzyl alcohol. [10] A process for making a synergistic antispasmodic, analgesic formulation as claimed in any one of the preceding claims, comprising the steps of [a] dissolving a dispensed quantity of preservatives and binder in a solvent one after one in a S.S. Container to form a binder solution; [b] transferring dispensed quantities of milled and/or sifted methocarbamol and nimesulide either in combined or separately with diluents in a planetary mixer with variable speed ranges from 12 to 40 rpm and mixing the active ingredients and diluents for 15 to 30 minutes at an ambient temperature below 25 degrees Celsius and relative humidity below 60% to obtain a first uniform mass; [c] transferring the binder solution slowly to the contents of planetary mixer and rotating the planetary mixer at slow speed for 10 to 20 minutes till a first uniform dough is formed; [d] passing the dough to a multimill fitted with sieves of diameter ranging from 10 mm to 14 mm at medium speed to produce wet granules; [e] transferring the wet granules to a drier for drying at 50° C to 55° C' [f] passing the dried granules to 16-mesh sieve through vibrosifter and passing retained granules through multimill using 1.5mm screen at a speed of 10 to 20 rpm to obtain dried uniformly sized granules; [g] lubricating the granules by passing the uniformly sized dried granules of the active ingredients to a double cone blender together with dispensed quantities of sifted lubricants, flavors, sweeteners, glidants, and disintegrating agents and mixing for 10 to 20 minutes to obtain lubricated granules; and [h] compressing the lubricated granules at a compression pressure of 3 to 10 kg/sq cm at temperatures between 20°C to 30°C and relative humidity;, below 60% to form dispersible tablets. Dated this 4th day of April, 2005. MOHAN DEWAN OF R.K.DEWAN & COMPANY APPLICANT'S PATENT ATTORNEY

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