An oral liquid formulation of methocarbamol

Abstract

The invention relates to an oral liquid suspension of methocarbamol (25-200 mg / mL) with one or more pharmaceutically acceptable excipients, and at least one vehicle and a flavoring agent. The preferre

Description

RELATED APPLICATION This application claims priority to IN Patent Application Nos. 202321067771 filed on October 10, 2023, and 202421034276 filed on April 30, 2024, the subject matter of which is incorporated by reference in its entirety. FIELD OF THE INVENTION The present invention discloses an oral liquid formulation of methocarbamol. More particularly, the present invention is related to an oral liquid formulation of methocarbamol in the form of suspension. The invention also provides a process for the preparation of said oral liquid formulation of methocarbamol, and use of said oral liquid formulation of methocarbamol for the treatment of acute musculoskeletal pain. BACKGROUND OF THE INVENTION A muscle spasm also known as a charley horse, muscle cramp or twitch is a sudden, involuntary movement in one or more muscles. Most commonly it occurs in the thighs, calves, feet, hands, and arms. They can also occur in the abdomen or along the rib cage. Muscle spasms are typically harmless, but they may result in an inability to use the affected muscle for a short period of time. Muscle spasms can occur due to several causes, including a lack of nutrients, muscular tension or stress, dehydration, overuse of the muscle, increased demand of blood flow, or various underlying medical conditions. Skeletal muscle relaxants are class of drugs that are used to relax and reduce tension in the muscles. They are more simply referred to as muscle relaxants. Skeletal muscle relaxants are used for a variety of conditions, including musculoskeletal conditions such as low back pain, and spastic conditions such as multiple sclerosis, spinal cord injuries, and cerebral palsy. Some muscle relaxants work in brain or spinal cord to block or dampen down excessively stimulated nerve pathway. The skeletal muscle relaxants are generally classified into two categories: centrallyacting skeletal muscle relaxants, which work by depressing neuron activity in the CNS, and direct-acting skeletal muscle relaxants, which prevent the release of calcium ions from muscle cells. Centrally-acting muscle relaxants include cyclobenzaprine, methocarbamol, metaxalone, and chlorzoxazone, whereas among direct-acting skeletal muscle relaxants, dantrolene. Methocarbamol is a centrally-acting skeletal muscle relaxant approved for the treatment of acute musculoskeletal pain. Methocarbamol is used with rest, physical therapy, and other measures to relax muscles, and relieve pain and discomfort caused by strains, sprains, and other muscle injuries. Methocarbamol treats muscle pain, and stiffness. It works by calming overactive nerves in your body, which helps your muscles relax. Methocarbamol is commercially available, in particular as an oral tablet, and parenteral, under the trade names ROBAXIN, and ROBAXIN-750. The most common way people take medications is orally. Oral medications come in the form of solid tablets, capsules, chewable tablets or lozenges to be swallowed whole or sucked on, or as drinkable liquids such as drops, syrups, suspensions or solutions. The oral medications can be swallowed, chewed, or placed under the tongue to dissolve. Various oral formulations are available in the market. Oral medication is the common form of drug administration because of its advantages such as convenience of drug administration via the oral route, patient preference, cost-effectiveness, and ease of large-scale manufacturing of oral dosage forms. However, an oral liquid dosage formulation providing many advantages over solid dosage form like better patient compliance especially to pediatric, geriatric, or to patients having difficulty in swallowing, they are available in different flavors which masks the taste of drug, they are more quickly absorbed on administration and hence give quicker onset of action. Bioavailability refers to the extent a substance or drug becomes completely available to its intended biological destinations. More accurately, bioavailability is a measure of the rate and fraction of the initial dose of a drug that successfully reaches either, the site of action or the bodily fluid domain from which the drug's intended targets have unimpeded access. There are the various factors which affects bioavailability. For any oral dosage form, the ultimate goal is the release of the drug into the GI tract for absorption and subsequent delivery to the target organ via the bloodstream. The oral tablet formulation involves disintegration followed by dissolution then absorption of drug in the solution form. However, in liquid dosage forms faster absorption as there is no need of disintegration step and hence quicker onset of action. Hence, liquid formulations have a higher bioavailability than solid oral dosage forms. Moreover, the liquid dosage forms are useful for the people who find it difficult to swallow the solid forms of medication. Currently, there is no oral liquid formulation of methocarbamol is present in the market. Hence, there is need to develop an oral liquid formulation of methocarbamol which will overcome the above stated disadvantages of solid dosage form. Thus, the inventors in the present invention have arrived to an oral liquid formulation of methocarbamol with aims to overcome problems cited above by preparing an oral liquid formulation of methocarbamol as described herein. OBJECTIVES OF THE INVENTION The main objective of the present invention is to develop an oral liquid formulation of methocarbamol. Another objective of this invention is to provide an oral liquid formulation of methocarbamol for treatment of acute musculoskeletal pain. Yet another objective of this invention is to provide an oral liquid formulation of methocarbamol which is having dose accuracy, flexibility, and uniformity of dosage. Yet another objective of this invention is to provide an oral liquid formulation of methocarbamol which is stable, and provides better patient compliance. Yet another objective of this invention is to provide an oral liquid formulation of methocarbamol which gives faster absorption, and quicker onset of action. SUMMARY OF THE INVENTION The present invention is all about to provide an oral liquid formulation of methocarbamol. The main aspect of the present invention is to provide an oral liquid formulation of methocarbamol comprises methocarbamol; an antimicrobial agent; a suspending agent; a viscosity modifying agent; one or more pH modifying agent, and one or more pharmaceutically acceptable excipients. Another aspect of the present invention provides a process for the preparation of an oral liquid formulation of methocarbamol. One more aspect of the present invention is to provide an oral liquid formulation of methocarbamol for treatment of acute musculoskeletal disorders associated with painful muscle spasms. DETAILED DESCRIPTION OF THE INVENTION The main embodiment of the present invention is an oral liquid formulation of methocarbamol. Before elaborating on the present invention in detail, it is to be understood that this invention is not limited to particularly exemplified examples or process parameters that may, of course, vary. It is also to be understood that the terminology used herein is to describe particular embodiments of the invention only, and is not intended to limit the scope of the invention in any manner. The detailed description set forth below is intended as a description of exemplary embodiments and is not intended to represent the only forms in which the exemplary embodiments may be constructed and / or utilized. The description sets forth the functions and the sequence of steps for constructing and / or operating the exemplary embodiments. However, it is to be understood that the same or equivalent functions and sequences which may be accomplished by different exemplary methods are also intended to be encompassed within the spirit and scope of the invention. As defined herein, all scientific and technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Although any process and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are now described. As stated in the present invention herein, the singular forms “a,” “an” and “the” specifically also encompass the plural forms of the terms to which they refer, unless the content clearly dictates otherwise. The term “about” is used herein to means approximately, in the region of, roughly, or around. As stated herein, that it follows in a transitional phrase or in the body of a claim, the terms “comprise(s)” and “comprising” are to be interpreted as having an open-ended meaning. That is, the terms are to be interpreted synonymously with the phrases “having at least” or “including at least”. When used in the context of a process, the term “comprising” means that the process includes at least the recited steps, but may include additional steps. When used in the context of a formulation, the term “comprising” means that the formulation includes at least the recited features or components, but may also include additional features or components. As stated herein, that follows in a transitional phrase or in the body of a claim, the term “consisting of’ excludes any element, step, or ingredient not specified in the claim or description. “Consisting of’ is defined as “closing the claim or description to the inclusion of materials other than those recited except for impurities ordinarily associated therewith”. As stated herein, that it follows in a transitional phrase or in the body of a claim, the term “consisting essentially of’ limits the scope of a claim to the specified materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the claimed invention. As used herein, the term “active agent” can be understood to include any substance or formulation or combination of substances or composition of matter when administered to a human or animal subject, induces a desired pharmacologic and / or physiologic effect by local and / or systemic action. The terms are used interchangeably herein: "active", "drug", “therapeutic agent”, “active pharmaceutical agent”, and "active ingredient". A “therapeutically effective amount” or “effective amount” is that amount of a pharmaceutical agent to achieve a pharmacological effect. The term “therapeutically effective amount” includes, for example, a prophylactically effective amount. As used herein, the term “therapeutically effective amount” can be understood to include an amount of methocarbamol that is effective in preventing or ameliorating a condition requiring an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions. As used herein the word “liquid formulation” refers to liquid oral formulation like solution, suspension or emulsion, more preferably in the form of suspension. As used herein, the terms “dose” and “dosage” can be understood to mean a specific amount of active or therapeutic agents for administration. The term “about” is used synonymously with the term “approximately.” As one of ordinary skill in the art would understand, the exact boundary of “about” will depend on the component of the formulation. Illustratively, the use of the term “about” indicates that values slightly outside the cited values, i.e., plus or minus 0.1 % to 10 %, which are also effective and safe. Thus, formulations slightly outside the cited ranges are also encompassed by the scope of the present claims. However, when the term “about” is used in connection with pH, it should be considered as plus or minus 2 unit of the pH value. By the term "pH", as used herein, is meant "apparent pH" wherein the pH measurement is carried out on the methocarbamol containing formulation in final form, for example, by measuring the pH of the formulation. The term “pH modifying agent” used herein refers to agents which provide stability and pH control to the pharmaceutical formulations. Herein the words “pH modifying agent” and “buffering agent” are used interchangeably. The term “antimicrobial agent” used herein refers to a chemical substance that is used to preserve pharmaceuticals from decomposition or fermentation by preventing the growth of microorganisms. Herein the words “antimicrobial agent” and “preservatives” are used interchangeably. As used herein, the term “viscosifying agent” can be interchangeably used with the term “viscosity modifying agent” and “thickening agent” as all are the same. As per one preferred embodiment, the term “ready-to-use” used herein is defined as the suspension that can administered directly to a patient for a treatment without the steps such as reconstitution or dilution. As stated herein the term “RTU” refers to ready-to-use and can interchangeably use for the “ready-to-use” phrase. The main embodiment of the present invention is to provide an oral liquid formulation of methocarbamol comprises methocarbamol; an antimicrobial agent; a suspending agent; a viscosity modifying agent; one or more pH modifying agent to provide a pH of about 3 to about 5; at least one vehicle, and one or more pharmaceutically acceptable excipients. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol having a particle size distribution of: D(0.10) not more than 25 pm, more preferably not more than 20 pm, and most preferably not more than 10 pm, D(0.50) not more than 50 pm, more preferably not more than 40 pm, and most preferably not more than 25 pm, and D(0.90) not more than 150 pm, more preferably not more than 100 pm, and most preferably not more than 70 pm, wherein the particle size determinations performed using suitable instrumentation, e.g., By Malvern method. As per preferred embodiment of the present invention, methocarbamol having a particle size distribution of: D(0.10) - 6.166 pm, D(0.50) - 17.985 pm, and D(0.90) - 47.679 pm. As per one embodiment of the present invention, methocarbamol can be present in the formulation of the present invention in an amount from about 1 mg / mL to about 500 mg / mL, preferably in the range from about 1 mg / mL to about 400 mg / mL, preferably in the range from about 1 mg / mL to about 300 mg / mL, more preferably in the range from about 1 mg / mL to 200 mg / mL, about 10 mg / mL to 500 mg / mL, preferably in the range from about 10 mg / mL to about 400 mg / mL, preferably in the range from about 10 mg / mL to about 300 mg / mL, more preferably in the range from about 10 mg / mL to 200 mg / mL, about 25 mg / mL to about 500 mg / mL, preferably in the range from about 25 mg / mL to about 400 mg / mL, preferably in the range from about 25 mg / mL to about 300 mg / mL, more preferably in the range from about 25 mg / mL to 200 mg / mL, or any other value in between thereof. As per one embodiment of the present invention, an antimicrobial agent can be selected from but not limited to benzoic acid, potassium sorbate, sodium benzoate, chlorobutanol, ethanol, butyl paraben, propyl paraben, methyl paraben, ethyl paraben, benzalkonium chloride, benzethonium chloride, benzyl alcohol, chlorobutanol, mcresol, myristyl gamma picolinium chloride, phenol, 2-phen oxy ethanol, phenyl mercuric nitrate, phenyl ethyl alcohol, and EDTA, or any combination thereof. As per preferred embodiment of the present invention, an antimicrobial agent used in the present invention is sodium benzoate. As per one embodiment of the present invention, an antimicrobial agent or sodium benzoate can be used in the range from about 0.01 mg / mL to about 20 mg / mL, preferably in the range from about 0.01 mg / mL to about 15 mg / mL, more preferably in the range from about 0.05 mg / mL to about 15 mg / mL, and most preferably in the range from about 0.05 mg / mL to about 10 mg / mL, or any other value in between thereof As per one embodiment of the present invention, suspending agent can be selected from but not limited to xanthan gum, guar gum, locust bean gum, gum tragacanth, a combination of microcrystalline cellulose, and sodium carboxymethylcellulose, microcrystalline cellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, hydroxypropyl cellulose, and magnesium aluminium silicate, or any combination thereof. As per preferred embodiment of the present invention, suspending agent used in the present invention is magnesium aluminium silicate. As per one embodiment of the present invention, suspending agent or magnesium aluminium silicate can be used in the range from about 1 mg / mL to about 25 mg / mL, preferably in the range from about 1 mg / mL to about 20 mg / mL, more preferably in the range from about 1 mg / mL to about 15 mg / mL, and most preferably in the range from about 1 mg / mL to about 10 mg / mL, or any other value in between thereof. As per one embodiment of the present invention, viscosity modifying agent can be selected from methyl cellulose, hydroxyethyl cellulose, bentonite, hectorite, magnesium aluminium silicate, microcrystalline cellulose, sodium carboxymethyl cellulose, hydroxy propyl methyl cellulose (HPMC), xanthan gum, acacia, tragacanth, alginates, guar gum, and colloidal silicon dioxide, or any combination thereof As per preferred embodiment of the present invention, viscosity modifying agent used in the present invention is sodium carboxymethylcellulose. As per one embodiment of the present invention, viscosity modifying agent or sodium carboxymethylcellulose can be used in the range from about 1 mg / mL to about 25 mg / mL, preferably in the range from about 1 mg / mL to about 20 mg / mL, more preferably in the range from about 1 mg / mL to about 15 mg / mL, and most preferably in the range from about 1 mg / mL to about 10 mg / mL, or any other value in between thereof. As per one embodiment of the present invention, one or more pH modifying agent can be selected from sodium citrate, sodium acetate trihydrate, phosphate, citric acid monohydrate, tris, succinate, histidine, glycine, arginine, malic, tartaric, acetic, benzoic, gluconic, glyceric, lactic, adipic, ascorbic, carbonic, glutamic, ammonium chloride, trisodium citrate dihydrate, triethanolamine, and salts or acids thereof, or any combination thereof. As per one embodiment of the present invention, one or more pH modifying agent can be preferably combination of two pH modifying agents. As per preferred embodiment of the present invention, combination of trisodium citrate dihydrate, and citric acid monohydrate is used as pH modifying agent. As per one embodiment of the present invention, trisodium citrate dihydrate or one or more pH modifying agent can be used in the range from about 0.5 mg / mL to about 30 mg / mL, preferably in the range from about 0.5 mg / mL to about 20 mg / mL, more preferably in the range from about 1 mg / mL to about 20 mg / mL, and most preferably in the range from about 1 mg / mL to about 15 mg / mL, or any other value in between thereof. As per one embodiment of the present invention, citric acid monohydrate or one or more pH modifying agent can be used in the range from about 0.5 mg / mL to about 30 mg / mL, preferably in the range from about 1 mg / mL to about 30 mg / mL, more preferably in the range from about 1 mg / mL to about 25 mg / mL, and most preferably in the range from about 1 mg / mL to about 20 mg / mL, or any other value in between thereof. As per one embodiment of the present invention, one or more pH modifying agent present in the suspension are citric acid monohydrate and trisodium citrate dihydrate, ratio of citric acid monohydrate:trisodium citrate dihydrate is between about 4:3 to 4:2, preferably 4:3 to 1:1 more preferably in the range of 3:1.5 to 2.5:1. As per another embodiment of the present invention, one or more pharmaceutically acceptable excipients can be selected from a humectant, a sweetening agent, a flavouring agent, or any combination thereof. As per another embodiment of the present invention, one or more pharmaceutically acceptable excipients can be used in the range from about 0.01 mg / ml to about 500 mg / ml, more preferably in the range from about 0.1 mg / ml to about 400 mg / ml, and most preferably in the range from about 0.5 mg / ml to about 400 mg / ml, or any other value in between thereof. As per one embodiment of the present invention, humectant can be selected from glycerol, hyaluronic acid, salicylic acid, alpha hydroxy acids (AHAs), such as glycolic acid, and lactic acid, propylene glycol, honey, and sorbitol, or any combination thereof. As per preferred embodiment of the present invention, glycerol is used as humectant. As per one embodiment of the present invention, humectant or glycerol can be used in the range from about 1 mg / mL to about 700 mg / mL, preferably in the range from about 1 mg / mL to about 500 mg / mL, more preferably in the range from about 100 mg / mL to about 500 mg / mL, and most preferably in the range from about 100 mg / mL to about 400 mg / mL, or any other value in between thereof. As per one embodiment of the present invention, sweetening agent can be selected from but not limited to glucose, sucralose, trehalose, fructose, xylose, dextrose, galactose, tagatose, maltose, sucrose, glycerol, dulcitol, mannitol, lactitol, sorbitol, xylitol, saccharine or the corresponding sodium, potassium or calcium salt, cyclamate or the corresponding sodium or calcium salt, aspartame, or acesulfame or the potassium salt thereof, ammonium glycyrrhizinate, alitame, inulin, isomalt, neohesperidin dihydrochalcone, neotame, thaumatin, and the like, or any combination thereof. As per preferred embodiment of the present invention, sucralose is used as sweetening agent. As per one embodiment of the present invention, sweetening agent or sucralose can be used in the range from about 1 mg / mL to about 50 mg / mL, preferably in the range from about 1 mg / mL to about 30 mg / mL, more preferably in the range from about 1 mg / mL to about 25 mg / mL, and most preferably in the range from about 10 mg / mL to about 25 mg / mL, or any other value in between thereof. As per one embodiment of the present invention, flavoring agent can be selected from but not limited to vanilla, citrus oil, including lemon, orange, grape, lime, and grapefruit, and fruit essences, including apple, banana, pear, peach, strawberry, raspberry, cherry, plums pineapple, apricot, peppermint, tutti frutti flavor, and so forth, and the like, or any combination thereof. As per preferred embodiment of the present invention, tutti frutti flavor is used as flavoring agent. As per one embodiment of the present invention, flavoring agent or tutti frutti flavor can be used in the range from about 0.01 mg / mL to about 5 mg / mL, preferably in the range from about 0.05 mg / mL to about 5 mg / mL, more preferably in the range from about 0.5 mg / mL to about 5 mg / mL, and most preferably in the range from about 0.5 mg / mL to about 3 mg / mL, or any other value in between thereof. Vehicle can be considered as any inert substance, or mixture of substances, added to increase the volume of the liquid formulation of present invention in order to make the liquid formulation of the present invention in a suitable form. As per one embodiment of the present invention, at least one vehicle can be selected from purified water, glycerol, phosphate buffer, propylene glycol, glycerin containing buffers, or any combination thereof. As per preferred embodiment of the present invention, purified water is used as vehicle. As per one embodiment of the present invention, vehicle or purified water can be used to adjust the final volume of the formulation. As per one embodiment of the present invention, the pH of the liquid oral formulation of methocarbamol is in the range from about 2 to about 7, more preferably in the range from about 3 to about 6, and most preferably in the range from about 3 to about 5. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol comprises about 25 mg / mL to about 200 mg / mL methocarbamol; an antimicrobial agent; a suspending agent; a viscosity modifying agent; one or more pH modifying agent; a humectant; a sweetening agent; a flavoring agent, and at least one vehicle. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol comprises therapeutically effective amount of methocarbamol; a suspending agent; a viscosity modifying agent; one or more pH modifying agent; a humectant; one or more pharmaceutically acceptable excipients, and at least one vehicle. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol consisting of therapeutically effective amount of methocarbamol; an antimicrobial agent; a suspending agent; a viscosity modifying agent; one or more pH modifying agent; a humectant; a sweetening agent; a flavoring agent, and at least one vehicle. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol consisting essentially of therapeutically effective amount of methocarbamol; an antimicrobial agent; a suspending agent; a viscosity modifying agent; one or more pH modifying agent; a humectant; one or more pharmaceutically acceptable excipients, and at least one vehicle. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol comprises about 25 mg / mL to about 200 mg / mL methocarbamol; one or more pharmaceutically acceptable excipients, and at least one vehicle; wherein one or more pharmaceutically acceptable excipient is selected from group consisting of an antimicrobial agent; a suspending agent; a viscosity modifying agent; one or more pH modifying agent; a humectant; a sweetening agent, and a flavoring agent. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol comprises about 2.5 % w / w to about 20 % w / w methocarbamol; one or more pharmaceutically acceptable excipients in an amount from about 0.01 % w / w to about 99 % w / w, and at least one vehicle; wherein one or more pharmaceutically acceptable excipient is selected from group consisting of an antimicrobial agent; a suspending agent; a viscosity modifying agent, one or more pH modifying agent; a humectant; a sweetening agent, and a flavoring agent. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol comprises about 25 mg / mL to about 200 mg / mL methocarbamol; magnesium aluminium silicate as a suspending agent; sodium carboxymethylcellulose as a viscosity modifying agent; one or more pH modifying agent; glycerol as a humectant, and water as a vehicle. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol comprises about 25 mg / mL to about 200 mg / mL methocarbamol; about 1 mg / mL to about 10 mg / mL magnesium aluminium silicate as a suspending agent; about 1 mg / mL to about 10 mg / mL sodium carboxymethylcellulose as a viscosity modifying agent; one or more pH modifying agent; about 100 mg / mL to about 400 mg / mL glycerol as a humectant, and water as a vehicle; wherein an oral liquid formulation has a pH from about 3 to about 6. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol comprises about 1 mg / mL to about 500 mg / mL methocarbamol; about 0.01 mg / mL to about 20 mg / mL sodium benzoate as an antimicrobial agent; about 1 mg / mL to about 25 mg / mL magnesium aluminium silicate as a suspending agent; about 1 mg / mL to about 25 mg / mL sodium carboxymethylcellulose as a viscosity modifying agent; about 0.5 mg / mL to about 30 mg / mL trisodium citrate dihydrate as a pH modifying agent; about 0.5 mg / mL to about 30 mg / mL citric acid monohydrate as a pH modifying agent; about 1 mg / mL to about 700 mg / mL glycerol as a humectant; about 1 mg / mL to about 50 mg / mL sucralose as a sweetening agent; about 0.01 mg / mL to about 5 mg / mL tutti frutti flavor as a flavoring agent, and water as a vehicle. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol comprises about 25 mg / mL to about 200 mg / mL methocarbamol; about 0.05 mg / mL to about 10 mg / mL sodium benzoate as an antimicrobial agent; about 1 mg / mL to about 10 mg / mL magnesium aluminium silicate as a suspending agent; about 1 mg / mL to about 10 mg / mL sodium carboxymethylcellulose as viscosity modifying agent; about 1 mg / mL to about 15 mg / mL trisodium citrate dihydrate as a pH modifying agent; about 1 mg / mL to about 20 mg / mL citric acid monohydrate as a pH modifying agent; about 100 mg / mL to about 400 mg / mL glycerol as humectant; about 10 mg / mL to about 25 mg / mL sucralose as sweetening agent; about 0.5 mg / mL to about 3 mg / mL tutti frutti flavor as a flavoring agent, and water as a vehicle. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol comprises about 150 mg / mL methocarbamol; about 5 mg / mL sodium benzoate as an antimicrobial agent; about 4 mg / mL magnesium aluminium silicate as a suspending agent; about 5.4 mg / mL sodium carboxymethylcellulose as a viscosity modifying agent; about 5.37 mg / mL trisodium citrate dihydrate as a pH modifying agent; about 14.80 mg / mL citric acid monohydrate as a pH modifying agent; about 300 mg / mL glycerol as a humectant; about 19 mg / mL sucralose as a sweetening agent; about 2 mg / mL tutti frutti flavor as a flavoring agent, and water as a vehicle. As per one embodiment of the present invention, the method of preparation of an oral liquid formulation of methocarbamol comprises steps of: mixing together methocarbamol; a suspending agent; a viscosity modifying agent; one or more pH modifying agent; a humectant, and water as a vehicle. Preferably the method includes adding of purified water in a stainless-steel vessel with stirring. Preferably the method includes adding of suspending agent, and viscosity modifying agent to form a uniform dispersion. Preferably the method includes adding of one or more pH modifying agent, and sweetening agent. Preferably the method includes adding of humectant. Preferably the method includes adding of antimicrobial agent, and flavoring agent. Preferably the method includes adding of methocarbamol API. Preferably the method includes homogenizing, and observing the pH of the dispersion. Preferably the method includes the step of adjusting the volume with purified water, and stirring. Preferably the method includes filling the suspension in the suitable container i.e. bottle. Preferably the method includes sealing and packing the bottle. As per another main embodiment of the present invention, the process of preparation of an oral liquid formulation of methocarbamol comprises steps: a. Adding purified water in a stainless-steel vessel with stirring; b. Adding suspending agent, and viscosity modifying agent in the solution of step (a) to form a uniform dispersion; c. Decreasing the speed of the stirring; d. Adding one or more pH modifying agent, and sweetening agent in the solution of step (c), and mixing with stirring for 30 minutes; e. Adding humectant in the solution of step (d), and homogenizing it for 15 minutes; f. Adding the antimicrobial agent, and flavoring agent sequentially in step (e), and homogenizing for 15 minutes; g. Adding methocarbamol API in step (f), and mixing till get a dispersion medium; h. Homogenizing the solution of step (g) for 60 minutes; i. Observing the pH of the dispersion of step (h); j. Adjusting the volume of the solution of step (i) with purified water, and stirring continuously for 20 minutes; k. The final formulation of step (j) was stored in amber glass bottle, and CRC capping of bottle. As per one embodiment of the present invention, the oral liquid formulation of methocarbamol has a viscosity in the range from about 50 cps to about 700 cps, preferably in the range from about 50 cps to about 500 cps, more preferably in the range from about 100 cps to about 400 cps, and most preferably in the range from about 100 cps to about 200 cps. As per one embodiment of the present invention, the oral liquid formulation can be selected from solution or suspension, more preferably suspension. According to one embodiment, an oral liquid formulation of methocarbamol is stable for 1 month, 3 months, and 6 months at 40 °C ± 2 °C / 75 % RH or 25 °C ± 2 °C / 60 % RH± 5 % RH or 30 °C ± 2 °C / 65 % RH. According to one embodiment, an oral liquid formulation of methocarbamol is stable for 1 month, 3 months, 6 months, 12 months, 18 months, 24 months or longer time at 40 °C ± 2 °C / 75 % RH or 25 °C ± 2 °C / 60 % RH ± 5 % RH or 30 °C ± 2 °C / 65 % RH. According to one embodiment, an oral liquid formulation of methocarbamol is stable 40 °C ± 2 °C / 75 % RH or 25 °C ± 2 °C / 60 % RH ± 5 % RH or 30 °C ± 2 °C / 65 % RH for at least 6 months. According to one embodiment, an oral liquid formulation methocarbamol has a total impurities are less than 1.0 % and any single unspecified impurities are less than 0.2 % after 1 month, 3 months, and 6 months of storage at 40 °C ± 2 °C / 75 % RH or 25 °C ± 2 °C / 60 % RH ± 5 % RH or 30 °C ± 2 °C / 65 % RH. As per one embodiment of the present invention, the said oral liquid formulation of methocarbamol when administered as a single dose to a subject under fasted condition which provides a geometric least square ranges of pharmacokinetic profiles like maximum plasma concentration (Cmax) from about 10000 ng / mL to about 20000 ng / ml; area under the plasma concentration versus time curve from time 0 to the last measurable concentration time (AUCo-t) from about 25000 hr*ng / mL to about 40000 hr*ng / mL, and area under the plasma concentration versus time curve from time 0 to infinity (AUCo-«) from about 25000 hr*ng / mL to about 40000 hr*ng / mL. As per one embodiment of the present invention, the said oral liquid formulation of methocarbamol when administered as a single dose to a subject under fasted condition which provides a geometric least square ranges of pharmacokinetic profiles like maximum plasma concentration (Cmax) 15024.64 ng / ml; area under the plasma concentration versus time curve from time 0 to the last measurable concentration time (AUCo-t) 32827.15 hr*ng / mL, and area under the plasma concentration versus time curve from time 0 to infinity (AUCo «>) 33224.25 hr*ng / mL. As per one embodiment of the present invention, the said oral liquid formulation of methocarbamol, when administered as a single dose to a subject has a T / R ratio from 80 % to 125 %. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol is stable and provides better patient compliance. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol useful for treatment of an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions. As per one embodiment of the present invention, an oral liquid formulation of methocarbamol comprises a therapeutically effective amount of methocarbamol for use as a medicament for the treatment of an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions. As per one embodiment of the present invention, a package comprising an oral liquid formulation of methocarbamol any one of the preceding aspects contained in a sealed bottle and packaging material comprising written instructions for use. The invention is further illustrated by the following examples which are provided to be exemplary of the invention and do not limit the scope of the invention. While the present invention has been described in terms of its specific embodiments, certain modifications, and equivalents will be apparent to those skilled in the art, and are intended to be included within the scope of the present invention. EXAMPLES EXAMPLE 1: SOLUBILITY OF METHOCARBAMOL Solubility of Methocarbamol was carried out in different vehicles at various pH conditions, and the results are tabulated below: Result: Sr. No. Medium Solubility (mg / ml) Vol. req. to dissolve 1500 mg API (ml) 1 0.1NHC1 15.47 100.00 2 pH 4.5 acetate buffer 16.86 88.96 3 pH 6.8 phosphate buffer 14.10 106.38 4 pH 7.2 phosphate buffer 13.64 109.96 5 Purified water 15.30 98.02 Table 1: Solubility of methocarbamol Based on above data it can be concluded that Methocarbamol is having high solubility in all pH media. Therefore, purified water is finalized to be used as a vehicle. EXAMPLE 2: DRUG - EXCIPIENTS COMPATIBILITY STUDY Primary selection of excipients was based on the excipients listed by the reference product (ROBAXIN Tablet) and on excipients commonly used for oral suspension dosage form. Compatibility study was conducted to investigate, and predict physico-chemical interactions between drug substance and excipients and to select the excipients during formulation development. Method: Accurately weighed quantity of methocarbamol, and individual excipients were mixed as per ratio mentioned in the drug - excipient compatibility table. Mixtures were filled in glass vials, plugged using LDPE plugs which were manually punctured. Filled glass vials were exposed to temperature and humidity conditions i.e. 60 °C ± 2 °C, and 40 °C ± 2 °C / 75 ± 5 % RH for 4 weeks. Result: Sr. No. Description Ratio Initial 60° C (4 weeks) 40° C / 75 % RH (4 weeks) 1. Methocaibamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate 750mg:0mg Off White dispersion No Significant Change No Significant Change 2. Methocaibamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: glycerol 750mg:1000mg Off White dispersion No Significant Change No Significant Change 3. Methocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: sucralose 750mg:150mg Off White dispersion No Significant Change No Significant Change 4. Methocaibamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydratc &sodium citrate: maltitol liquid 750mg:5000mg Off White dispersion No Significant Change No Significant Change 5. Methocaibamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: sucrose 750mg:1500mg Off White dispersion No Significant Change No Significant Change 6. Methocaibamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: carmellose sodium 750mg:20mg Off White dispersion No Significant Change No Significant Change 7. Methocaibamol API dispersed in purified water at Ph 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: VEEGUM K 750mg:400mg Off White dispersion No Significant Change No Significant Change 8. Methocaibamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydratc &sodium citrate: sodium benzoate 750mg:25mg Off White dispersion No Significant Change No Significant Change 9. Methocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: sodium lauryl sulphate 750mg:10mg Off White dispersion No Significant Change No Significant Change 10. Methocaibamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid 750mg:10mg Off White dispersion No Significant Change No Significant Change monohydrate &sodium citrate: methyl parahydroxy benzoate 11. Methocaibamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: lemon flavour 750mg:20mg Off White dispersion No Significant Change No Significant Change 12. Methocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: peppermint flavour 750mg: 20mg Off White dispersion No Significant Change No Significant Change 13. Methocaibamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: aspartame 750mg:20mg Off White dispersion No Significant Change No Significant Change 14. Methocaibamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: stearic acid 750mg:1125mg Off White dispersion No Significant Change No Significant Change Table 2: Results of physical appearance for drug-excipient compatibility study Sr. No. Sample Condition Guaifenesin Guaifenesin B isomer Methocarbamol Isomer Methocarbamol Dioxolone Highest Unknown Impurity Total Impurity Source of Impurity Process / Degradation Process Process / Degradation Process / Degradation Specifications NMT 0.15 % NMT 0.15 % NMT 0.15 % NMT 0.15 % NMT 0.10 % NMT 1.0 % 1 Methocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate Initial 0.11 % 0.00 % 0.01 % 0.00 % 0.00 % 0.12% 60°C for 1 month 1.27% 0.00 % 0.73 % 1.37% 0.03 % 3.40% 40°C / 75% RH for 1 month 0.14% 0.00 % 0.02 % 0.04 % 0.00 % 0.20 % 2 Methocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: glycerol Initial 0.11 % 0.00 % 0.00 % 0.00 % 0.00 % 0.12% 60 C for 1 month 1.14% 0.00 % 1.07% 0.95 % 0.00 % 3.16% 40“C / 75% RH for 1 month 0.15% 0.00 % 0.03 % 0.04 % 0.00 % 0.22 % 3 Methocarbamol API dispersed in purified water at Initial 0.11 % 0.00 % 0.01 % 0.00 % 0.00 % 0.12% 60 C for 1 month 0.12% 0.00 % 0.02 % 0.01 % 0.00 % 0.15% pH 4 (3-5) adjusted with citric acid monohydrate & sodium citrate: sucralose 40“C / 75% RH for 1 month 0.14% 0.00 % 0.02 % 0.03 % 0.00 % 0.19% 4 Methocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: maltitol liquid Initial 0.11% 0.00 % 0.01 % 0.00 % 0.00 % 0.12% 60°C for 1 month 0.27 % 0.00 % 0.82 % 0.17% 0.01 % 1.27% 40°C / 75% RH for 1 month 0.11 % 0.00 % 0.03 % 0.01 % 0.00 % 0.15% 5 Methocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: sucrose Initial 0.12% 0.00 % 0.01 % 0.00 % 0.00 % 0.13 % 60°C for 1 month 0.75 % 0.02 % 0.68 % 0.92 % 0.12% 2.67 % 40°C / 75% RH for 1 month 0.13 % 0.00 % 0.02 % 0.03 % 0.00 % 0.19% 6 Methocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: carmellose sodium Initial 0.11% 0.00 % 0.01 % 0.00 % 0.04 % 0.16% 60‘C for 1 month 1.37% 0.01 % 0.84 % 1.38% 0.00 % 3.61 % 40°C / 75% RHfor 1 month 0.15% 0.00 % 0.02 % 0.04 % 0.00 % 0.21 % 7 Methocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: VEEGUM K (Magnesium Aluminium Silicate) Initial 0.11 % 0.00 % 0.02 % 0.00 % 0.09 % 0.23 % 60°C for 1 month 1.52% 0.02 % 3.22% 1.51 % 0.02 % 6.29 % 40“C / 75% RH for 1 month 0.14% 0.01 % 0.06 % 0.08 % 0.09 % 0.39 % 8 Methocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: sodium benzoate Initial 0.11 % 0.00 % 0.01 % 0.00 % 0.01 % 0.14% 60°C for 1 month 1.46% 0.01 % 0.77 % 1.51 % 0.00 % 3.76% 40“C / 75% RH for 1 month 0.16% 0.00 % 0.02 % 0.05 % 0.01 % 0.24 % 9 Methocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: sodium lauryl sulphate Initial 0.11 % 0.00 % 0.01 % 0.01 % 0.03 % 0.16% 60°C for 1 month 1.03 % 0.00 % 0.66 % 1.27% 0.00 % 2.97 % 40°C / 75% RHfor 1 month 0.15% 0.00 % 0.02 % 0.05 % 0.00 % 0.22 % 10 Methocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: methyl parahydroxy benzoate Initial 0.11 % 0.00 % 0.01 % 0.01 % 0.00 % 0.13 % 60°C for 1 month 0.88 % 0.00 % 0.53 % 1.11% 0.00 % 2.52 % 4O‘C / 75% RHfor 1 month 0.15% 0.00 % 0.02 % 0.04 % 0.00 % 0.22 % 11 Medrocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: lemon flavour Initial 0.11 % 0.00 % 0.01 % 0.00 % 0.00 % 0.13 % 60°C for 1 month 0.78 % 0.00 % 0.53 % 0.95 % 0.00 % 2.26 % 40°C / 75% RHfor 1 month 0.15% 0.00 % 0.02 % 0.04 % 0.00 % 0.20 % 12 Methocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: peppermint flavour Initial 0.11 % 0.00 % 0.01 % 0.00 % 0.00 % 0.12% 60°C for 1 month 1.20% 0.00 % 0.76 % 1.29% 0.01 % 3.27% 40 C / 75% RHfor 1 month 0.15% 0.00 % 0.02 % 0.04 % 0.00 % 0.21 % 13 Methocarbamol API dispersed in purified water at pH 4 (3-5) adjusted with citric acid monohydrate &sodium citrate: aspartame Initial 0.11 % 0.00 % 0.01 % 0.01 % 0.00 % 0.13 % 60°C for 1 month 0.92 % 0.00 % 0.53 % 1.11 % 0.01 % 2.58 % 40"C / 75% RHfor 1 month 0.14% 0.00 % 0.02 % 0.04 % 0.02 % 0.23 % 14 Methocarbamol API dispersed in Purified Water at pH 4 (3-5) adjusted with Citric Acid Initial 0.03 % 0.00 % 0.00 % 0.00 % 0.00 % 0.03 % 60°C for 1 month 0.43 % 0.00 % 0.11 % 0.82% 0.00 % 1.36% 40°C / 75% RH for 1 month 0.03 % 0.00 % 0.01 % 0.01 % 0.00 % 0.05 % Monohydrate &Sodium Citrate: Stearic Acid NMT: Not More Than: RH: Relative Humidity Table 3: Results of related substance for drug excipient compatibility study Based on above data, it was observed that in presence of aqueous media guaifenesin impurity was observed to be increased up to 0.11 % level at initial itself, which further crossed 0.15 % level when stored at 60 °C temperature condition. At 60 °C temperature condition all impurity levels (except unknown impurity) were observed to be higher in almost all drug:excipient combinations. This indicates probable instability of methocarbamol in aqueous phase at higher temperature conditions. After 1 month storage at 40 °C / 75 %RH condition, slight increase in guaifenesin impurity from initial level was observed for all API / excipient combinations. API / aluminium magnesium silicate combination also showed rise in levels of methocarbamol isomer &Methocarbamol di oxoIone impurities (above 0.05 %) after 1 month storage at 40°C / 75 %RH condition. EXAMPLE 3: FORMULATION OF ORAL LIQUID SUSPENSION OF METHOCARBAMOL (CRL-007-039) Sr. Name of Material Qty / Unit Qty / Unit No. mg / inl mg / 5 ml 1 Methocarbamol 150.00 750.00 2 Sodium benzoate 5.00 25.00 3 Glycerol 300.00 1500.00 4 Aluminium magnesium silicate 6.00 30 5 Colloidal silicon dioxide 20.00 100.00 6 Citric acid monohydrate 11.60 58.02 7 Sodium citrate (Trisodium citrate dihydrate) 5.366 26.83 8 Sucralose 19.00 95.00 9 Tutti-fruity flavor 2.00 10.00 10 Purified water Q.S. Q.S. Q.S.: Quantity Sufficient Table 4: Formulation of oral liquid suspension of methocarbamol Procedure: a) The buffering agents was dissolved in purified water and mixed with continuous stirring for 30 minutes; b) The preservative was added to the solution of step (a) and mixed with continuous stirring for 30 minutes; c) The suspending and thickening agents were dissolved to solution of step (b) and mixed with continuous stirring for 180 minutes; d) The humectant was added to solution of step (c) and mixed with continuous stirring for 30 minutes; e) The sweetening agent was added to solution of step (d) and mixed with continuous stirring for 10 minutes; f) The methocarbamol was added to solution of step (e) and mixed with continuous stirring for 60 minutes; g) The flavouring agent was added to solution of step (f) and mixed with continuous stirring for 10 minutes; h) The formulated dispersion of step (g) was homogenized for 30 minutes; i) The final formulation of step (h) was stored in amber glass bottle &child resistant closure (CRC) capping of bottle. EXAMPLE 4: COMPARATIVE EVALUATION OF ROBAXIN-750 TABLETS AND METHOCARBAMOL 750MG / 5ML ORAL SUSPENSION Sr. No. Parameter ROBAXIN-750 Methocarbamol 750 mg / 5 ml Oral Suspension 1 Description White to off white, capsule shaped film coated tablets having score-line on one side and embossed with ‘3009’ on another side. White to off white liquid suspension free from lumps and coagulated mass. 2 Dosage Form Tablet Oral Suspension 3 Batch No. 14LA CRL-007-039 4 Assay of Methocarbamol 99.6 % 103.9% 5 Preservative Content NA 99.4 % 6 pH 3.42 (2 tablets / 10 ml purified water) 4.60 7 Related Substances Guaifenesin 0.00 % Guaifenesin 0.03 % (3 isomer 0.00 % P isomer Not Detected Methocarbamol isomer Not Detected Methocarbamol isomer 0.00 % Methocarbamol Dioxolone Not Detected Methocarbamol Dioxolone Not Detected Highest unknown impurity 0.00 % Highest unknown impurity 0.01 % Total impurities 0.00 % Total impurities 0.04 % Table 5: Comparative evaluation of ROBAXIN-750 tablets and methocarbamol 750 mg / 5 ml oral suspension EXAMPLE 5: COMPARATIVE DISSOLUTION STUDY OF 5 METHOCARBAMOL 750 MG / 5 ML ORAL SUSPENSION (#CRL-007-039) VS ROBAXIN-750MG TABLET (#14LA) The dissolution condition of methocarbamol tablets USP was adopted. Dissolution medium Purified water / 0.1 N HC1 / 0.1 N HC1 (PEAK Vessel) / pH 4.5 acetate buffer / pH 4.5 acetate buffer (PEAK Vessel) / pH 6.8 phosphate buffer / pH 6.8 phosphate buffer (PEAK vessel) Apparatus 900 ml Volume Paddle (USP Type II) Speed 50 RPM Recommended Sampling Time points (Minutes) 5, 10. 15. 30. 45, 60 minutes USP: United States Pharmacopeia; RPM: Rotates Per Minutes Table 6: Dissolution conditions 10 Product % Drug Release in Purified water (Average) F2 5 min 10 min 15 min 30 min 45 min 60 min ROBAXIN 750 mg Tablet 16% 77% 93 % 101 % 101 % 101 % Both Test &Reference product were releasing more than 85% within 15 minutes Methocarbamol 750 mg / 5 ml Oral Suspension 102 % 102 % 103 % 103 % 103 % 103 % Table 7: % Drug release in purified water It was observed that the product was completely released within 15 minutes. So, it can be concluded that, oral suspension formulation (CRL-007-039) is also fast 15 releasing similar to tablet formulation. Product % Drug Release (Average) in 0.1 N HCL F2 5 min 10 min 15 min 30 min 45 min 60 min ROBAXIN 750 mg Tablet 13 % 63% 76% 92% 97% 99 % F2 less than 50 Methocarbamol 750 mg / 5 ml Oral Suspension 99% 99 % 99% 99% 99 % 100 % Product % Drug Release (Average) in .1 N HCL (PEAK Vessel) F2 5 min 10 min 15 min 30 min 45 min 60 min ROBAXIN 750 mg Tablet 28% 87% 96% too % 100 % 101 % Both Test &Reference product were releasing more than 85 % within 15 minutes Methocarbamol 750 mg / 5 ml Oral Suspension 99% 99% 99% 99% 99 % 100 % Table 8: % Drug Release in 0.1 N HCL and 0.1 N HCL (PEAK Vessel) Initially, heap formation in dissolution vessel was observed for ROBAXIN tablets. Due to which dissolution rate was slower. So, it was decided to perform dissolution 5 with using PEAK Vessel. It was observed that the product was completely released within 15 minutes. So, it can be concluded that, oral suspension formulation (CRL-007-039) is also fast releasing similar to tablet formulation. Product % Drug Release (Average) in pH 4.5 acetate buffer F2 5 min 10 min 15 min 30 min 45 min 60 min ROBAXIN 750 mg Tablet 5% 18% 35% 79% 97% 99% Less than 50 Methocarbamol 750 mg / 5 ml Oral Suspension 96% 96% 97% 97% 97% 97% Product % Drug Release (Average) in pH 4.5 acetate buffer (PEAK Vessel) F2 5 min 10 min 15 min 30 min 45 min 60 min ROBAXIN 750 mg Tablet 8% 27% 47% 100 % 101 % 103 % Less than 50 Methocarbamol 750 mg / 5 ml Oral Suspension 96% 96% 97% 97% 97% 97% Table 9: % Drug release in pH 4.5 acetate buffer and pH 4.5 acetate buffer (PEAK Vessel) Initially, heap formation in dissolution vessel was observed for ROBAXIN tablets. Due to which dissolution rate was slower. So, it was decided to perform dissolution with using PEAK vessel. Dissolution profile of oral suspension formulation (CRL-007-039) was found to be faster than ROBAXIN, till 15 minutes time point. However, observed to be releasing completely at 30 minutes time point. Product % Drug release* Average) in pH 6.8 phosphate buffer F2 5 min 10 min 15 min 30 min 45 min 60 min ROBAXIN 750 mg Tablet 4 15 28 67 91 98 Less than 50 Methocarbamol 750 mg / 5 ml Oral Suspension 98 99 99 99 99 99 Product % Drug release (Average) in pH 6.8 phosphate buffer (PEAK vessel) F2 5 min 10 min 15 min 30 min 45 min 60 min ROBAXIN 750 mg Tablet 6 22 39 96 102 103 Less than 50 Methocarbamol 750 mg / 5 ml Oral Suspension 98 99 99 99 99 99 Table 10: % Drug release in pH 6.8 phosphate buffer and pH 6.8 phosphate buffer (PEAK Vessel) Initially, heap formation in dissolution vessel was observed for ROBAXIN tablets. Due to which dissolution rate was slower. To confirm slower release profile of ROBAXIN is only due to heap formation, it was decided to perform dissolution studies in peak vessels. Dissolution profile of oral suspension formulation (CRL-007-039) was found to be faster than ROBAXIN, till 15 minutes time point. However, observed to be releasing completely at 30 minutes time point. From the results of in-vitro dissolution data, it is observed that in 0.1 N HCL, both the products were releasing completely i.e. (Reference: 96%; Test: 99% within 15 minutes). From dissolution data it can be concluded that after oral administration both suspension and tablet, it will get dissolved completely in stomach (pH 1.2) environment before its transit to the intestine. Dissolution in pH 4.5 &6.8 will not have significance for absorption as complete dissolution is reached before gastric emptying. EXAMPLE 6: STABILITY DATA OF ORAL LIQUID FORMULATION OF 5 METHOCARBAMOL (CRL-007-039) The stability study was conducted for 3 and 6 months at 40°C / 75 % RH &25°C / 60 % RH. Result: Parameter Specification Stability Tests Initial 40°C / 75% RH 25°C / 60% RH (3M) (6M) (3M) (6M) Assay of Methocarbamol 95-105 % 99.3% 97.6% 98.8% 96.7% 99.8% Sodium Benzoate Content 80 % 120 % 96.6% 96.5% 96.7% 95.5% 97.6% pH 3.54.5 4.07 3.95 3.90 Specific Gravity 1.10 ± 1.0 1.14 1.12 1.10 Viscosity NLT 25 cps 25.86 40.50 28.80 Related Substances Guaifenesin 0.15% 0.06% 0.04% 0.12% 0.03% 0.03% Guaifenesin p isomer 0.15% ND ND ND ND ND methocarbamol isomer 0.15% 0.02% 0.01% 0.05% ND ND Methocarbamol dioxolone 0.15% 0.03% 0.02% 0.04% ND ND Highest unknown impurity 0.10% ND ND ND ND ND Total impurities 1.0% 0.12% 0.06% 0.21% 0.03% 0.03% Dissolution Test (Purified Water, Apparatus Type II, 900 ml, at 50 RPM) 5 min 99 97 99 97 99 10 min 100 98 100 98 100 15 min 100 98 101 98 100 30 min 100 98 101 98 100 45 min 100 98 101 98 101 60 min 100 98 101 98 101 M: Months; ND: Not Detected; RPM: Rotates Per Minutes; CPS: Centipoise; NLT: Not Less 10 Than; RH: Relative Humidity Table 11: Stability study data of oral liquid formulation of methocarbamol (CRL-007-039) The optimized formulation was found to be stable at 40°C / 75% RH &25°C / 60% 15 RH up to 6 Months. EXAMPLE 7: FORMULATION OF ORAL LIQUID SUSPENSION OF METHOCARBAMOL (Bl) Sr. No. Name of Material Quantity / Unit ing / ml 1 Methocarbamol 1-500 2 Sodium benzoate 0.01-20 3 Glycerol 1-700 4 Magnesium aluminium silicate 1-25 5 Sodium carboxymethylcellulose 1-25 6 Citric acid monohydrate 0.5-30 7 Trisodium citrate dihydrate 0.5-30 8 Sucralose 1-50 9 Tutti-fruity flavor 0.01-5 10 Purified water Q.S. Q.S.: Quantity Sufficient Table 12: Formulation of oral liquid suspension of methocarbamol (Bl) EXAMPLE 8: FORMULATION OF ORAL LIQUID SUSPENSION OF METHOCARBAMOL (B2) Sr. No. Name of Material Qty / Unit mg / ml 1 Methocarbamol 25-200 2 Sodium benzoate 0.05-10 3 Glycerol 100-400 4 Magnesium aluminium silicate 1-10 5 Sodium carboxymethylcellulose 1-10 6 Citric acid monohydrate 1-20 7 Trisodium citrate dihydrate 1-15 8 Sucralose 10-25 9 Tutti-fruity flavor 0.5-3 10 Purified water Q.S. Q.S.: Quantity Sufficient Table 13: Formulation of oral liquid suspension of methocarbamol (B2) 10 EXAMPLE 9: FORMULATION OF ORAL LIQUID SUSPENSION OF METHOCARBAMOL (B3) Sr. No. Name of Material Quantity / Unit Quantity / Unit Quantity / Unit mg / ml mg / 5 ml % w / v 1 Methocarbamol 150.00 750.00 15 2 Sodium benzoate 5.00 25.00 0.5 3 Glycerol 300.00 1500.00 30 4 Magnesium aluminium silicate 4.00 20.00 0.4 5 Sodium carboxymethylcellulose 5.4 27.00 0.54 6 Citric acid monohydrate 14.804 74.02 1.480 7 Trisodium citrate dihydrate 5.366 26.83 0.536 8 Sucralose 19.00 95.00 1.9 9 Tutti-fruity flavor 2.00 10.00 0.2 10 Purified water Q.S. Q.S. Q.S. Q.S.: Quantity Sufficient Table 14: Formulation of oral liquid suspension of methocarbamol (B3) Procedure: a. The purified water was added in a stainless-steel vessel with stirring; b. The magnesium aluminium silicate and sodium carboxymethylcellulose were added in the solution of step (a) to form a uniform dispersion; c. The speed of the stirring was decreased; d. Trisodium citrate dihydrate, citric acid monohydrate and sucralose were added in the solution of step (c) and mixing with stirring for 30 minutes; e. The glycerol was added in the solution of step (d) and homogenized it for 15 minutes; f. The sodium benzoate and Tutti Frutti flavor were added sequentially in step (e) and homogenizing for 15 minutes; g. The methocarbamol API was added in step (f) and mixed till get a dispersion medium; h. Homogenized the solution of step (g) for 60 minutes; i. Observed the pH of the dispersion if step (h); j. Adjusted the volume of the solution of step (i) with purified water and stirred continuously for 20 minutes; k. The final formulation of step (j) was stored in amber glass bottle &CRC capping of bottle. EXAMPLE 10: COMPARATIVE EVALUATION OF METHOCARBAMOL 750MG / 5ML WITH ORTOTON® RECORDATI 750 MG FILM COATED TABLETS AND ROBAXIN "-750 FILM COATED TABLET Sr. No. Physical &chemical Parameters ORTOTON® Recordati 750 mg Film coated tablets ROBAXIN*-750 film coated Tablets Formulation B3 (750 mg / 5 ml) 1. Description White, slightly convex, oblong film-coated tablets with a score line on both sides White to off white, capsule shaped film coated tablets having score-line on one side and embossed with ‘3009’ on another side. Off white, viscous oral suspension. 2. pH Not applicable Not applicable 3.68 3. Viscosity Not applicable Not applicable 610.5 cps 4. Assay (%) 98.0% 99.6% 99.6% 5. Specific gravity' Not applicable Not applicable 1.1318 6. Preservative content (Sodium benzoate) Not applicable Not applicable 96.6% 7. Related Substances Guaifenesin 0.03% 0.002% ND Guaifenesin p- Isomer ND 0.001% 0.01% Methocarbamol Isomer 0.01% ND 0.01% Methocarbamol Dioxolone ND ND ND Single maximum unknown impurity ND 0.00% 0.00% Total Impurity 0.04% 0.003% 0.02% 8. Dissolution Study: Media: Purified Water, Volume: 900 ml, Apparatus: Paddle; Speed: 50 RPM Time points (Min.) % Drug released % RSD % Drug released %RSD % Drug released %RSD 5 30 17.32 16 9.67 23 5.08 10 78 7.13 77 9.64 30 4.55 15 91 3.01 93 5.16 43 2.30 30 99 0.88 101 0.94 65 4.61 45 100 0.60 101 0.78 90 3.72 60 101 0.65 101 1.09 96 1.02 ND: Not Detected; RPM: Rotates Per Minutes; CPS: Centipoise; RSD: Relative Standard Deviation Table 15: Comparative evaluation of methocarbamol 750 mg / 5 ml with 5 ORTOTON® Recordati 750mg film coated tablets and ROBAX1N "-750 film coated tablet The results indicates that all physical and chemical parameters were found satisfactory. Also, dissolution profile of formulation B3 was found similar with 10 marketed formulations. EXAMPLE 11: STABILITY DATA OF FORMULATION B3 The stability study was conducted for 3 and 6 months at 40 °C / 75 % RH &25 °C / 60 %RH. 5 Result: Parameters Specification Stability Condition Initial 40°C / 75% RH IM 40°C / 75% RH 3M 40°C / 75% RH 6M 25°C / 60% 3M 25°C / 60% RH 6M 30°C / 65% RH 6M Description Off white, viscous oral suspension. Off white, viscous oral suspension. Assay (%) 95 - 105% 99.6% 100.2% 100.1% 100.4% 99.3% 100.7% 100.8% PH 3.2-4.8 3.68 3.85 3.88 3.91 3.85 3.92 3.94 Sodium Benzoate Content 80 - 120% 24.15m g / 5ml 24.351m g / 5ml 23.509m g / 5ml 23.93mg / 5ml 23.755m g / 5ml 23.35mg / 5ml 23.31m g / 5ml Specific Gravity 1.100 ±0.1 1.1318 1.1322 1.1285 1.1274 1.1253 1.1275 1.1311 Related Substances Guaifenesin 0.15% 0.01% 0.02% 0.04% 0.08% 0.01% 0.01% 0.02% P-isomer 0.15% ND ND ND ND ND ND ND Dioxolone 0.15% ND ND ND ND ND ND ND Methocarbam ol Isomer 0.15% 0.01% 0.01% 0.02% 0.03% 0.01% 0.01% 0.01% Highest Unknown Impurity 0.10% 0.00% 0.01% 0.03% 0.03% 0.00% 0.00% 0.01% Total Impurities 1.0% 0.02% 0.04% 0.09% 0.14% 0.02% 0.02% 0.04% Dissolution Purified Water, 900 ml, Paddle 50 RPM Time points (Min.) NLT 75% (Q) of the labeled amount of Methocarbamol dissolved in 45 minutes % release % release % release % release % release % release % release 10 30 33 55 75 36 38 68 15 43 49 68 83 49 50 83 30 65 74 86 93 80 79 96 45 90 87 94 99 95 98 99 60 96 96 98 101 99 99 101 ND: Not Detected; RPM: Rotates Per Minutes; NLT: Not Less Than; Q: Quantity; M: Months; RH: Relative Humidity Table 16: Stability study data of formulation B3 The results indicates that the final formulation was found to be stable at 40°C / 75% RH &25°C / 60% RH up to 6 Months. 5 EXAMPLE 12: PHOTO STABILITY STUDY A. Photostability study Procedure: Photostability study was performed on the formulation B3. Results: Sr. No. Test parameters Stability Product Specificatio n Methocarbamol API (Batch no: A) Finished product (Formulation- B3) Initial API in open Exposed Conditio n API in Protected Conditio n (Control) Initial Open exposed drug product outside of the immediate pack Drug product in the immediate (primary pack) Protected samples (enwrapped in aluminum foil) are used as dark controls) 1. Description Off white, viscous oral suspension. White Bulky Powder odorless Off white, viscous oral suspension. 2. Viscosity (cps) NLT 400 cps - 610.5 546.0 591.0 603.0 3. pH 3.2-4.8 - - - 3.73 3.87 3.84 3.82 4. Specific Gravity 1.100 ±0.1 - - - 1.1319 1.1347 1.1340 1.1386 5. Assay (%) 95 - 105% 99.3% 99.8% 99.2% 101.2% 103.2% 103.4% 102.6% 6. Sodium Benzoate Content (%) 80 - 120% - - - 98.1% 101.3% 99.5% 100.8% 7. Related Substances i P-Isomer 0.15% ND ND ND ND ND ND ND ii Guaifenesin 0.15% 0.03% 0.01% 0.01% 0.01% 0.01% 0.01% 0.01% iii Methocarba mol Isomer 0.15% ND 0.02% 0.01% 0.01% 0.01% 0.01% 0.01% iv Dioxolone 0.15% ND ND ND ND ND ND ND V Highest Unknown Impurity 0.10% ND ND ND 0.00% 0.01% 0.00% 0.00% vi Total Impurities 1.0% 0.03% 0.03% 0.02% 0.02% 0.03% 0.02% 0.02% 8. Dissolution Profile N = 6 Units Media- Purified Water; Media Volume- 900 ml at 37°C; Apparatus - 2 (Paddle); Speed - 50 RPM; Time Points - 5.10.15,30,45,60 Time points (In Minutes) - - - - % Drug Release d (% RSD) % Drug Released (% RSD) % Drug Released (% RSD) % Drug Released (% RSD) 5 - - - - 17 (6.55) 25 (11.85) 20 (11.89) 18 (4.79) 10 - - - - 29 (6.44) 41 (9.97) 33 (7.19) 30 (4.78) 15 - - - - 42 (3.89) 55 (8.28) 44 (5.63) 43 (5.30) 30 - - - - 68 (2.89) 81 (6.76) 74 (2.62) 71 (4.44) 45 - - - - 88 (3.28) 93 (5.56) 89 (2.06) 87 (3.74) 60 - - - - 95 (3.45) 98 (4.38) 100 (1.01) 99 (3.33) ND: Not Detected; RPM: Rotates Per Minutes; CPS: Centipoise; RSD: Relative Standard Deviation; NLT: Not Less Than Table 17: Results of photostability study 5 The results indicates that the final formulation was found to be stable at Photostability condition. EXAMPLE 13: FREEZE THAW STUDY Sr. No. Batch No. Condition Cycle 1 Formulation B3 Upright 'b 3 Testing condition Step 1: Freezer (-20°C) for 48 Hrs. Step 2: Accelerated temperature (40°C / 75% RH) for 48 Hrs. Table 18: Freeze thaw study details Methocarbamol 750mg / 5ml Oral Suspension B. No Formulation B3 Condition INITIAL Freeze thaw stability after 3 cycles Description Off while, viscous oral suspension. Off white, viscous oral suspension. Viscosity 610.5 cps 633.0 cps PH 3.73 3.86 Specific Gravity 1.1319 1.1359 Methocarbamol Assay 101.2% 103.1% Sodium Benzoate 98.1% 99.9% Related Substances P-Isomer ND ND Guaifenesin 0.01% 0.01% Methocarbamol Isomer 0.01% 0.01% Dioxolone ND ND Highest Unknown Impurity 0.00% 0.00% Total Impurities 0.02% 0.02% Dissolution Profile N = 6 Units Media- Purified Water; Media Volume- 900 ml at 37°C; Apparatus - 2 (Paddle); Speed - 50 RPM; Time Points - 5,10,15,30,45,60 Time (In Minutes) % Drug Released % RSD % Drug Released % RSD 5 17 6.55 14 8.02 10 29 6.44 26 3.94 15 42 3.89 37 2.97 30 68 2.89 62 2.49 45 88 3.28 76 3.07 60 95 3.45 86 4.06 ND: Not Detected; RPM: Rotates Per Minutes; CPS: Centipoise; RSD: Relative Standard Deviation; NLT: Not Less Than Table 19: Results of freeze-thaw study 5 The results indicates that the final formulation was found to be stable at freeze thaw condition. EXAMPLE 14: RELATIVE PHARMACOKINETIC ANALYSIS 10 Comparative pharmacokinetic analysis of methocarbamol oral suspension of batch B3 was conducted with methocarbamol tablets in normal, healthy, adult human volunteers under fasting condition. Relative pharmacokinetic analysis (i.e. geometric least squares means, ratio, 90 15 % confidence interval, 95 % upper confidence bound and power) of Test Product - T vs. Reference Product - R for methocarbamol are summarized in the following table: Parameters (Units) Geometric Least Squares Means 90% Confidence Interval (%) Intra Subject CV (%) Power (T / R) (%) Test Product - T Reference Product - R Ratio (T / R) % Ln Cmax (ng / mL) 15024.640 14942.355 100.55 82.02-123.27 32.09 56.60 Ln AUCo-t 32827.153 32913.450 99.74 92.85-107.14 11.03 99.87 (hr*ng / mL) Ln AUG, , (hr*ng / mL) 33224.254 33275.895 99.84 93.03-107.16 10.89 99.88 Table 20: Relative pharmacokinetic results for methocarbamol As per results, the test product has demonstrated bioavailable to the reference product with respect to Cmax, AUCo-t and AUCo / .

Claims

1. An oral liquid formulation of methocarbamol comprises about 25 mg / mL to about 200 mg / mL methocarbamol; one or more pharmaceutically acceptable excipients, and at least one vehicle; wherein one or more pharmaceutically acceptable excipient is selected from group consisting of an antimicrobial agent; a suspending agent; a viscosity modifying agent; one or more pH modifying agent; a humectant; a sweetening agent, and a flavoring agent.

2. An oral liquid formulation of methocarbamol comprises about 25 mg / mL to about 200 mg / mL methocarbamol; about 1 mg / mL to about 10 mg / mL magnesium aluminium silicate as a suspending agent; about 1 mg / mL to about 10 mg / mL sodium carboxymethylcellulose as a viscosity modifying agent; one or more pH modifying agent; about 100 mg / mL to about 400 mg / mL glycerol as a humectant; one or more pharmaceutically acceptable excipients, and water as a vehicle; wherein an oral liquid formulation has a pH from about 3 to about 6.

3. An oral liquid formulation of methocarbamol comprises methocarbamol; a suspending agent; a viscosity modifying agent; one or more pH modifying agent; a humectant; one or more pharmaceutically acceptable excipients, and at least one vehicle.

4. The oral liquid formulation of methocarbamol as claimed in claim 3, wherein the methocarbamol in the range from about 1 mg / mL to about 500 mg / mL, preferably in the range from about 1 mg / mL to about 400 mg / mL, more preferably in the range from about 25 mg / mL to about 200 mg / mL.

5. The oral liquid formulation of methocarbamol as claimed in claim 3, wherein said suspending agent can be selected from xanthan gum, guargum, locust bean gum, gum tragacanth, a combination of microcrystalline cellulose, and sodium carboxymethylcellulose, microcrystalline cellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, hydroxypropyl cellulose, and magnesium aluminium silicate, or any combination thereof.

6. The oral liquid formulation of methocarbamol as claimed in claim 3, wherein said viscosity modifying agent can be selected from methyl cellulose, hydroxyethyl cellulose, bentonite, hectorite, magnesium aluminium silicate, microcrystalline cellulose, sodium carboxymethyl cellulose, hydroxy propyl methyl cellulose (HPMC), xanthan gum, acacia, tragacanth, alginates, guar gum, and colloidal silicon dioxide, or any combination thereof.

7. The oral liquid formulation of methocarbamol as claimed in claim 3, wherein said one or more pH modifying agent can be selected from sodium citrate, sodium acetate trihydrate, phosphate, citric acid, tris, succinate, histidine, glycine, arginine, malic, tartaric, acetic, benzoic, gluconic, glyceric, lactic, adipic, ascorbic, carbonic, glutamic, ammonium chloride, triethanolamine, and salts or acids thereof, or any combination thereof.

8. The oral liquid formulation of methocarbamol as claimed in claim 3, wherein said humectant can be selected from glycerol, hyaluronic acid, salicylic acid, alpha hydroxy acids (AHAs), such as glycolic acid, and lactic acid, propylene glycol, honey, and sorbitol, or any combination thereof.

9. The oral liquid formulation of methocarbamol as claimed in claim 3, wherein said at least one vehicle can be selected from purified water, glycerol, phosphate buffer, propylene glycol, glycerin containing buffers, or any combination thereof.

10. The oral liquid formulation of methocarbamol as claimed in claim 3, comprises about 1 mg / mL to about 25 mg / mL magnesium aluminiumsilicate as a suspending agent; about 1 mg / mL to about 25 mg / mL sodium carboxymethylcellulose as a viscosity modifying agent; about 0.5 mg / mL to about 30 mg / mL trisodium citrate dihydrate, and citric acid monohydrate as a one or more pH modifying agent; about 1 mg / mL to about 700 mg / mL glycerol as a humectant, and water as a vehicle.

11. The oral liquid formulation of methocarbamol as claimed in claim 3, wherein said oral liquid formulation can be selected from solution, or suspension, more preferably in the form of suspension.

12. A method of preparation of an oral liquid formulation of methocarbamol comprises steps ofmixing together methocarbamol; a suspending agent; a viscosity modifying agent; one or more pH modifying agent; a humectant; one or more pharmaceutically acceptable excipients, and water as a vehicle.

13. The method of preparation of an oral liquid formulation as claimed in claim 12, comprising the steps of:the said method includes adding of purified water in a stainless-steel vessel with stirring;the said method includes adding of suspending agent, and viscosity modifying agent to form a uniform dispersion;the said method includes adding of one or more pH modifying agent, and sweetening agent;the said method includes adding of humectant;the said method includes adding of antimicrobial agent, and flavoring agent; the said method includes adding of methocarbamol API;the said method includes homogenizing, and observing the pH of the dispersion;the said method includes the step of adjusting the volume with purified water, and stirring;the said method includes filling the suspension in the suitable container i.e. bottle;the said method includes sealing and packing the bottle.5 14. An oral liquid formulation of methocarbamol comprises a therapeuticallyeffective amount of methocarbamol; an antimicrobial agent; a suspending agent; a viscosity modifying agent; one or more pH modifying agent; a humectant; a sweetening agent; a flavoring agent, and at least one vehicle.10 15. The oral liquid formulation as claimed in claim 14, for use as a medicamentfor the treatment of an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions.