Title of Invention

A MUSCLE RELAXANT CUM ANALGESIC FORMULATION AND TO A METHOD OF MAKING THE SAME

Abstract

[1] An antispasmodic, analgesic formulation comprising a core consisting of (a) 250 mg to 1000 mg of methocarbamol (b) 125 to 500 mg of paracetamol (c) pharmaceutical acceptable inert excipients consisting of at least one diluent 5 % to 45 % of the total mass of the formulation, at least one binder being 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 being from 0.6% to 5% of the total mass of the formulation, and at least one disintegrant being 0.6% to 8% of the total mass of the formulation and optionally one film coat on the core consisting of at least one film forming polymer and a plasticizer that forms a layer of 2 to 4 wt % based on the weight of the core composition and optionally a preservative and a surfactant.

Full Text

FORM - 2 THE PATENTS ACT, 1970 (39 of 1970) & THE PATENTS RULES, 2003 COMPLETE (See section 10 and rule 13) A MUSCLE RELAXANT CUM ANALGESIC FORMULATION AND TO A METHOD OF MAKING THE SAME SANJEEV KHANDELWAL an Indian National of Prem Nivas, 13, Altamount Road, Mumbai 400 026 Maharashtra, India, GRANTED 22-11-2005 THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED. ORIGINAL 22 NOV 2005 FIELD OF INVENTION This invention relates to a synergistic muscle relaxant cum analgesic formulation and to a method of making the same. WHAT THE INVENTION ENVISAGES Particularly, this invention envisages a synergistic formulation composition containing methocarbamol and paracetamol. The fixed dose combination of methocarbamol and paracetamol produce a synergistic response in the effective relief of pain. In particular this invention envisages a tablet formulation for oral administration of methocarbamol and paracetamol. PHARMACOLOGY OF METHOCARBAMOL Skeletal Muscle Relaxants primarily act in the central nervous system to produce muscle relaxant effects. Methocarbamol is one of the most trusted drugs, approved by U.S. F.D.A, for treating Skeletal Muscle Spasm. The mechanism of action of Methocarbamol is obscure. However it acts by producing CNS depression although no action was found on the contractile mechanism of striated muscle and the motor ended plate or the nerve fibre. Methocarbamol is generally a fast acting drug with onset of action within 30 minutes after oral administration, while the peak serum level is achieved in 2 hours. Oral Methocarbamol is mainly indicated for painful skeletal muscle spasm of the dorsal region and also for spasm due to sports injuries. PHARMACOLOGY OF PARACETAMOL Paracetamol is one of the most widely used analgesics and is regarded to offer highest degree of safety and tolerabiliry in the recommended dose. Although its mode of action is not fully understood, Paracetamol is believed to inhibit cyclo- oxygenase (COX) in the central nervous system, besides exerting action on the peripheral pain chemoreceptors (Bradykinin). Like Methocarbamol, Paracetamol is immediately acting, thus has a matching pharmacokinetic profile. The said formulation combines the time tested Skeletal Muscle Relaxant, Methocarbamol and the safe analgesic, Paracetamol. The said formulation is quite useful for various Skeletal Muscle Spasms that are mild to moderate in nature. Therapeutic effective amount of methocarbamol used in the formulation is preferably as pure methocarbamol or any pharmaceutically acceptable form such as methocarbamol (micronised) or any other steriochemical pure form of it. Therapeutic effective amount of paracetamol used in the formulation is preferably paracetamol 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 may be coated with suitable film forming agents to obtain a layer of coat that mainly improve the product appearance. 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 paracetamol in a single dosage form. The method for treating a patient comprises orally administering a pharmaceutical formulation comprising a combination of (a) 250 mg to 1000 mg of methocarbamol the first active ingredient (b) 125 mg to 500 mg of paracetamol the second active ingredient (c) pharmaceutical acceptable inert excipients (d) a pharmaceutical acceptable carrier. According to this invention therefore there is provided a synergistic antispasmodic, analgesic formulation comprising a core consisting of (a) 250 mg to 1000 mg of methocarbamol (b) 125 to 500 mg of paracetamol (c) pharmaceutical acceptable inert excipients consisting of at least one diluent 5 % to 45 % of the total mass of the formulation, at least one binder being 0.1% to 4% of the total mass of the formulation, at least one glidant from 0.01% to i 3% of the total mass of the formulation, at least one lubricant being from 0.6% to 5% of the total mass of the formulation, and at least one disintegrant being 0.6% to 8% of the total mass of the formulation and optionally one film coat on the core consisting of at least one film forming polymer and a plasticizer that forms a layer of 2 to 4 wt % based on the weight of the core composition and optionally a preservative and a surfactant. 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 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, hydroxypropylmethuyl cellulose and mixture of these. 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 disintegrant is the disintegrant is at least one compound selected from a group of compounds which include starches, clays, cellulose derivatives including croscarmellose, gums, aligns including alginic acid,, combinations of hydrocarbonates with weak acids, crospovidone, sodium starch glycolate, agar, cation exchange resins, citrus pulp, veegum HV, natural sponge, and bentonite.cross-linked polyvinylpyrrolidone, carboxymethyl starch, natural starch, microcrystalline cellulose, cellulose gum and mixtures of these, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, croscarmellose sodium, guar gum, magnesium aluminum silicate, methyl cellulose, polacrihn potassium, powdered cellulose, pregelatinized starch, sodium alginate, and sodium starch glycolate. The coating layer of the formulation is preferably used to form a layer that which includes film forming cellulose polymers such as Ethyl Cellulose and/ or hydroxypropylmethylcellulose, hydroxy propyl cellulose, plasticizers such as propylene glycol, surfactants, coloring agents that may comprises at least one of the approved food and drug colors such as yellow iron oxides, tetrazine, brillant blue etc, solvents such as purified water, isopropyl alcohol, acetone, methylene chloride and opacifier includes titanium dioxide. The weight of the film coating layer preferably 2 to 4 wt % based on the weight of the core composition may be employed. 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 etc. The formulation 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 Ce 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 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. 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 Stainless Steel Container to form a binder solution; [b] transferring dispensed quantities of milled and/or sifted methocarbamol, paracetamol, 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 camylofln dihydrochloride 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, glidants, and disintegrating agents and mixing for 10 to 20 minutes to obtain lubricated granules; [h] compressing the lubricated granules at a compression pressure of 3 to 10 kg/sq cm . at Temperature between 20°C to 30°C and relative Humidity: Below 60% to form cores; [i] film coating the cores with at least one film coat comprising dispensed quantities of film forming polymer and plasticizer. The process of making the composition in accordance with this invention is as follows. The process involve the making core by 1. GRANULATION The granulation procedure is preferably followed to make the tableting process easier by increasing the bulk density of the active materials as well as the inert materials used. The granulation procedure performed by making the granules in a single entity using a single binder system so as to prepare uniform sized spherical shaped granules. Using machines such as planetary mixer, rapid granulation mixer or any other suitable mixers, usually perform this granulation method. 2. DRYING: The drying method is preferably followed to reduce the moisture content of the granules and thus to reduce the occurrences of any microbial growth which otherwise possible in excess moisture environment. Simultaneously the care is taken so that the moisture content should not fall below the critical limit. The very less amount of moisture may create the problem in compression process. Dry the wet granules in FBD/Tray Drier, Rake the granules while drying in a tray drier. Drying temperature 55 °C to 60 °C. 3. MILLING/ SIFTING: Pass dried granules through vibrosifter using 12 to 20 mesh and pass retained granules through multimill using 2.0 to 2.5 mm screen at medium speed. 4. LUBRICATION: The granules are mixed in double cone blender. And the sifted lubricants, glidants, surfactants, disintegrating agents and mix for 10 to 20 minutes. Lubricated granules obtained are ready for compression. 5. COMPRESSION: Environmental conditions: Temperature : Between 22°C to 25°C Relative Humidity : Below 60% A rotary compression machine is set up with suitable punches and dies and compression is started after complying with necessary parameters. 6. FILM-COATING PROCESS (OPTIONAL): The film coating can comprise of either two layers or one layers of coating. Environmental Conditions: Temperature : Between 20°C to 30°C Relative Humidity : Below 60% Preparation of the film coating solution: The film coating solution is prepared by the dispersing the film forming polymers, colors, and plasticizer in either organic solvents or aqueous solvents. The coating material composition contains coating polymer such as ethyl cellulose, hydroxypropylmethylcellulose, plasticizer such as propylene glycol, diethyl phthalate and at least coloring agent such as titanium dioxide, iron oxide black, quinoline yellow and other approved colors. 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 tablet contains: Methocarbamol 350 mg Paracetamol 250 mg MANUFACTURING PROCESS (Batch Size 1 Lakhs Tablet) Step - 1: Manufacturing of the granules 35 Kg of methocarbamol, 25 kg of paracetamol, 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. 0.7 kg of polyvinyl' pyrrolidone is mixed with 5 Kg of purified water in a stainless steel [s.s.] tank under continuous stirring to obtain a clear solution. Add 0.7 kg of sodium lauryl sulfate and dissolve it with stirring. Add the above said binder solution 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: 2.5 kg sodium starch glycollate, 0.4 kg of colloidal silicon dioxide, and 0.7 kg of magnesium stearate. This sifted mass (except magnesium stearate) along with 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. 0.7 kg of magnesium stearate; was then added to the blender and further blending was done for 5 minutes resulting in the lubricated core mass. Step - 3 : Compression This core mass was fed to hopper of a single rotary compression machine and the compression pressure was set at 4 kg/sq cm. 1,00,000 Cores were obtained: Dimension: round shape, Standard curvature, with dimension 12.7 mm +/- 0.1 mm Avg weight of core 650 mg ± 3 %. EXAMPLE - 2 Each tablet contains: Methocarbamol 3 5 0 mg Paracetamol 250 mg MANUFACTURING PROCESS (Batch Size 1 Lakhs Tablet) Step - 1: Manufacturing of the granules 35 Kg of methocarbamol, 25 kg of paracetamol, 3.0 kg of microcrystalline cellulose, 2.0 kg of cross carmellose sodium and 3.0 kg of microcrystalline cellulose 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 0.7 kg of polyvinyl pyrrolidone to 7 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 meshes the following materials were passed: 0.6 kg sodium lauryl sulfate, 2.0 kg of sodium starch glycollate, and 0.7 kg of magnesium stearate. This sifted mass (except magnesium stearate) along with 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. 0.7 kg of magnesium stearate; was then added to the blender and further blending was done for 5 minutes resulting in the lubricated core mass. Step - 3 : Compression This core mass was fed to hopper of a single rotary compression machine and the compression pressure was set at 4 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 core 690 mg ± 3 %. EXAMPLE - 3 Each tablet contains: Methocarbamol 500 mg Paracetamol 325 mg MANUFACTURING PROCESS (Batch Size 1 Lakhs Tablet) Step - 1: Manufacturing of the granules 50 Kg of methocarbamol, 32.5 kg of paracetamol, 5.0 kg of microcrystalline cellulose, and 1.0 kg of sodium lauryl sulfate 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 0.800 kg of polyvinyl pyrrolidone to 8 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 18 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 1.8%. 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: 0.4 kg of colloidal silicon dioxide, 2.0 kg of sodium starch glycollate and 1.0 kg of magnesium stearate. This sifted mass (except magnesium stearate) along with 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. 1.0 kg of magnesium stearate; was then added to the blender and further blending was done for 5 minutes resulting in the lubricated core mass. Step - 3 : Compression This core mass 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 core 932 mg ± 3 %. EXAMPLE - 4 Each tablet contains: Methocarbamol 250 mg Paracetamol 125 mg MANUFACTURING PROCESS (Batch Size 1 Lakhs Tablet) Step - 1: Manufacturing of the granules 25 Kg of methocarbamol, 12.5 kg of paracetamol, 4.0 kg of microcrystalline cellulose, 3.0 kg of microcrystalline cellulose and 1.0 kg of cross carmellose sodium 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. 1.50 kg of starch mixed with 2 Kg of purified water in a stainless steel [s.s.] tank under continuous stirring to obtain slurry. Simultaneously heat 5 kgs of purified water in a jacketed steam vessel till boiling. Add the above said slurry to this boiling purified water until the binder was completely dispersed in the solvent to form a translucent paste. The paste 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: 1.5 kg sodium starch glycollate, 0.500 kg of sodium lauryl sulfate and 0.6 kg of magnesium stearate. This sifted mass (except magnesium stearate) along with 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. 0.6 kg of magnesium stearate; was then added to the blender and further blending was done for 5 minutes resulting in the lubricated core mass. Step - 3 : Compression This core mass was fed to hopper of a single rotary compression machine and the compression pressure was set at 3 kg/sq cm. 1,00,000 Cores were obtained: Dimension: capsule shape, Standard curvature, Avg weight of core 456 mg ± 3 %. Step - 5: film - coating The cores were coated with a film coating. A coating suspension was prepared by mixing 0.2 kg of ethyl cellulose; and 0.4 kg of hydroxypropyl cellulose and mixed together with 6 kg of isopropyl alcohol and 11 kg of Methylene chloride; 0.01 kg of diethyl phthalate, 0.05 kg of titanium dioxide in a s.s. container, and stirred for five minutes using overhead stirrer until a smooth slurry was obtained. The coating solution was sieved through 80-mesh sieve. The de-dusted cores were transferred into a coating pan and the tablet bed was heated by inching process using hot air blower. The initial temperature was set at 40°C. Once the tablet bed attains 45°C it was ready for spray coating with the coating suspension. The cores were coated with the coating suspension. The relative humidity was maintained below 60 % throughout. The coated tablets were polished with talc. Final dimensions of the tablets were as follows: Dimension: capsule shape, Standard curvature, Avg weight of film coated tablet 462 mg ± 3 %. Trials were conducted by administering the tablets of the above examples to patients suffering from spasmodic pain. Patients were also administered paracetamol alone and separate tablets of paracetamol and methocarbamol. Significant results were obtained for the formulation of this invention over both paracetamol 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] An antispasmodic, analgesic formulation comprising a core consisting of (a) 250 mg to 1000 mg of methocarbamol (b) 125 to 500 mg of paracetamol (c) pharmaceutical acceptable inert excipients consisting of at least one diluent 5 % to 45 % of the total mass of the formulation, at least one binder being 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 being from 0.6% to 5% of the total mass of the formulation, and at least one disintegrant being 0.6% to 8% of the total mass of the formulation and optionally one film coat on the core consisting of at least one film forming polymer and a plasticizer that forms a layer of 2 to 4 wt % based on the weight of the core composition and optionally a preservative and a surfactant. [2] An antispasmodic, analgesic formulation as claimed in claim 1, in which the diluent is at least one diluent selected from a group of diluents comprising micorcrystalline cellulose, starches, lactose, mannitol, calcium phosphate, dibasic calcium phosphate and mixtures of these. [3] An antispasmodic, analgesic formulation as claimed in claim 1, in which the binder is at least one binder selected from a group of binders comprising pregelatinized starch, starches, gelatin, vinyl chloride, povidone, hydroxypropyl cellulose, ethyl cellulose, cellulose acetate phthalate, hydroxypropylmethuyl cellulose and mixture of these. [4] An antispasmodic, analgesic formulation as claimed in claim 1, in which the glidant is at least one glidant selected from a group of glidants comprising corn starch, talcum, colloidal silicon dioxide, silicon dioxide and mixtures of these. [5] An antispasmodic, analgesic formulation as claimed in claim 1, in which the lubricant is at least one lubricant selected from a group of lubricants comprising 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 fiimarate, stearic acid, surfactants, talc, waxes and zinc stearate. [6] An antispasmodic, analgesic formulation as claimed in claim 1, in which the disintegrant is the disintegrant is at least one compound selected from a group of compounds which include starches, clays, cellulose derivatives including croscarmellose, gums, aligns including alginic acid,, combinations of hydrocarbonates with weak acids, crospovidone, sodium starch glycolate, agar, cation exchange resins, citrus pulp, veegum HV, natural sponge, and bentonite.cross-linked polyvinylpyrrolidone, carboxymethyl starch, natural starch, microcrystalline cellulose, cellulose gum and mixtures of these, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, croscarmellose sodium, guar gum, magnesium aluminum silicate, methyl cellulose, polacrilin potassium, powdered cellulose, pregelatinized starch, sodium alginate, and sodium starch glycolate. [7] An antispasmodic, analgesic formulation as claimed in claim 1, in which the preservative is at least one preservative selected from a group of preservatives comprising the benzoic acid esters such as methyl paraben, propyl paraben, sodium benzoate and the like . [8] An antispasmodic, analgesic formulation as claimed in claim 1, in which the preservative is at least one surfactant selected from a group of surfactants comprising 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 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. [9] An antispasmodic, analgesic formulation as claimed in claim 1, in which the film forming polymer is at least one polymer selected from a group of polymers comprising cellulose polymers such as Ethyl Cellulose and/ or hydroxypropylmethylcellulose, hydroxy propyl cellulose along with plasticizers such as propylene glycol and solvents such as purified water, isopropyl alcohol, acetone, methylene chloride, [10] A process for making a synergistic antispasmodic, analgesic formulation as claimed in claim 1, consisting of the following steps [a] dissolving a dispensed quantity of preservatives and binder in a solvent one after one in a Stainless Steel Container to form a binder solution; [b] transferring dispensed quantities of milled and/or sifted methocarbamol, paracetamol, and diluent in a planetary mixer with variable speed ranges from 12 to 40 rpm and mixing the active ingredients and diluent 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 uniform dough is formed; I i [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 a 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 to a double cone blender together with dispensed quantities of sifted lubricants, glidants, and disintegrating agents and mixing for 10 to 20 minutes to obtain lubricated granules; [h] compressing the lubricated granules at a compression pressure of 3 to 10 kg/sq cm . at Temperature between 20°C to 30°C and relative Humidity : Below 60% to form cores; [i] film coating the cores with at least one film coat comprising dispensed quantities of film forming polymer and plasticizer. Dated this 7th day of March 2005. Mohan Dewan of R K Dewan & Co Applicant's Patent Attorney

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206-mum-2004-claims(granted)-(22-11-2005).doc

206-mum-2004-claims(granted)-(22-11-2005).pdf

206-mum-2004-correspondence(17-3-2008).pdf

206-mum-2004-correspondence(ipo)-(27-6-2008).pdf

206-mum-2004-form 1(23-2-2004).pdf

206-mum-2004-form 18(2-6-2005).pdf

206-mum-2004-form 2(granted)-(22-11-2005).doc

206-mum-2004-form 2(granted)-(22-11-2005).pdf

206-mum-2004-form 26(23-2-2004).pdf

206-mum-2004-form 3(18-4-2005).pdf

206-mum-2004-form 3(23-2-2004).pdf

206-mum-2004-form 4(29-3-2006).pdf

206-mum-2004-form 4(30-12-2004).pdf

206-mum-2004-form 5(9-3-2005).pdf

206-mum-2004-form 9(10-3-2005).pdf

206-mum-2004-pettition under rule 137(19-4-2005).pdf