Title of Invention	"A SUSTAINED RELEASE MONOTHILIC FORMULATION OF ROPINIROLE"
Abstract	The present invention discloses a simple, low cost solid dosage sustained release formulation of ropinirole which requires no specialized machinery and can utilize existing plant machinery, for manufacturing. The formulation differs from existing formulations in the same category, in being monolithic (consisting of a single block and not multiple layers).

Full Text

FIELD OF THE INVENTION The present invention relates to pharmaceutical formulations. More specifically, it pertains to a sustained release formulation of ropinirole which has therapeutic applications in Parkinson's disease, Restless leg syndrome and Fibromyalgia. BACKGROUND AND PRIOR ART Ropinirole is a novel dopamine D2 agonist used in the treatment of Parkinson's disease, Restless Leg Syndrome (RLS) and Fibromyalgia; the compound has a molecular weight of 296.84 and a melting point of approximately 247degree. C. Ropinirole hydrochloride has a solubility of 133 mg/ml in water at 20.degree. C. Earlier methods for treating Parkinsonism typically involved the use of L-Dopa; see, e.g., S. Fahn, "On-Off Phenomenon with L-Dopa Therapy in Parkinsonism: Clinical and Pharmacological Correlations and the Effect of Intramuscular Pyridoxine," Neurology 24:431-441 (1974) and C. D. Marsden et al., "On-Off Effects in Patients with Parkinson's Disease on Chronic Levadopa Therapy," Lancet 1:262-296 (1976). However, it is noted that patients undergoing treatment with L-Dopa have frequently experienced severe therapeutic response fluctuations, possibly resulting from decreased capacity to store newly synthesized dopamine within the brain as a consequence of the progressive degeneration of dopaminergic nerve terminals. (Marsden et al., supra, and R. J. Eden et al., "Preclinical Pharmacology of Ropinirole (SK&F 101468-A) a Novel Dopamine D2 Agonist," Pharmacol. Biochem. & Behavior 38:147-154 (1991). Also, as explained in U.S. Pat. No. 4,912,126, cited above, the combined administration of L-Dopa with a peripheral dopa-decarboxylase inhibitor such as carbidopa or benzaseride, as frequently done, can result in a number of adverse effects including nausea, vomiting, abdominal distension and psychiatric side-effects. Ropinirole has been developed as a drug which is effective in the treatment of Parkinson's disease but which overcomes the limitations associated with L-Dopa therapy. Additionally, ropinirole has been identified as a more specific dopamine D2 agonist than other dopamine agonists such as bromocriptine and pergolide. Fibromyalgia is a common disabling disorder characterized by chronic musculoskeletal aches and pain, stiffness, general fatigue, and sleep abnormalities including diminished stage four sleep. Fibromyalgia is a chronic, painful disorder commonly seen in rheumatology practice and is often viewed as a musculoskeletal pain process. Fibromyalgia is characterized as a reproducible, neurosensory processing abnormality associated with fatigue, and generalized muscular spasm, which most rheumatologists suspect is related to stage IV sleep deprivation. Examination of affected patients reveals increased tenderness at muscle and tendon insertion sites, known as "tender points". Fibromyalgia patients experience severe morning stiffness and a generalized decreased of overall physical function, and they are often prone to headaches, memory and concentration problems, dizziness, numbness and tingling, and crampy abdominal or pelvic pain. Fibromyalgia affects 2-4% of the population and is most frequently found in women between 20 and 50 years old, though it can also affect men, the elderly and minors. Restless legs syndrome (RLS) is a neurosensorimotor disorder with parestethesias, sleep disturbances and, in most cases, periodic limb movements of sleep (PLMS). Two forms of RLS appear to exist: the idiopathic and the uremic form. In this document both forms will be referred to as RLS. RLS is characterized by (1) a desire to move the legs, usually associated with paresthesias/dysesthesias, (2) motor restlessness, (3) worsening or exclusive presence of symptoms at rest (i.e. lying, sitting) with at least partial or temporary relief by activity, and (4) worsening of symptoms during the evening or night. Dopaminergic drugs have produced some interesting results. Dopaminergic agents are drugs that are usually used to treat Parkinson's disease and in some cases may appear to provide some short term relief for some people with RLS. RLS is not a form of Parkinson's disease but is a distinct neurologic condition. Several studies have shown that L-dopa given with a peripheral carboxylase inhibitor at a 10:1 ratio is effective in treating RLS. See for example the following articles: Brodeur C, Montplaisir J, Marinier R, Godbout R., "Treatment of RLS and PMS with L-dopa: a double-blind controlled study," Neurology; 35:1845-1848 (1988). Montplaisir J, Godbout R, Poirier G, Bedard M. A., "Restless legs syndrome and periodic movements in sleep: physiopathology and treatment with L-dopa," Clinical Neuropharmacology; 9:456-463 (1986). Von Scheele C, "Levodopa in restless legs," Lancet; 2:426-427 (1986). Akpinar S., "Restless legs syndrome treatment with dopaminergic drugs," Clinical Neuropharmacology; 10:69-79 (1987). Ropinirole was recently approved in the U.S. for this indication. Despite the efficacy of ropinirole in the treatment of these the aforesaid conditions, it suffers from a major disadvantage. Ropinirole has a relatively short half life of 2 - 10 hrs. This leads to substantial fluctuations in the plasma concentration of the drug in blood plasma, especially in cases of chronic administration. To maintain reasonably stable plasma concentrations of the drug in the blood, it is necessary to resort to frequent dosing, resulting in inconvenience to the patient and low patient compliance with the prescribed dosing regimen. Moreover, widely fluctuating plasma concentrations of the drug in blood may result in administration of less than therapeutic amounts of the drug in a conservative dosing regimen, or amounts too large for the particular patient in an aggressive dosing regimen. Thus, there is a need for a formulation which is capable of releasing ropinirole hydrochloride in a sustained manner over a 24 hour period so that administration of ropinirole is required only once per day, thereby ensuring optimal control of the symptoms of these diseases. US patent 5,807,570 discloses a transdermal patch for prolonged delivery of ropinirole. Transdermal patches also require specialized equipment and complex processing for manufacture, pose compliance problems and are impractical in hot and humid weather conditions. An oral controlled release formulation of ropinirole is disclosed in US patent application No. 20040247676 and WO patent No. 03035042. The formulation disclosed therein employs a multi-layered tablet to achieve constant release ropinirole over a period of 24 hrs. The product and process disclosed therein is complex requiring multiple steps and specialized machinery for manufacture. The formulation disclosed therein is a tablet consisting of multiple layers organized in various complex geometries. The layers have different compositions thus the process involves separately processing components of each of the layers and thereafter combining them using specialized machinery. Hence, there is yet a need in the prior art to provide an improved ropinirole formulation capable of releasing ropinirole in a sustained manner over a 24-hour period. To meet this need, the invention provides such a formulation. The current invention discloses simple compositions which can be manufactured by a simple process employing commonly available machinery and thus, are cheaper and offer easier process control and validation. OBJECTS OF THE INVENTION The main object of the invention is to provide a simple sustained release formulation of ropinirole and improved process for the manufacture of said sustained release formulation. BRIEF DESCRIPTION OF THE FIGURES FIG. 1 is a graph of the oral ropinirole formulation made with the process of Example 1. FIG. 2 is a graph of the oral ropinirole formulation made with the process of Example 2. FIG. 3 is a graph of the oral ropinirole formulation made with the process of Example 3. FIG. 4 is a graph of the oral ropinirole formulation made with the process of Example 4. FIG. 5 is a graphical representation of the release profile of a prior art product. DETAILED DESCRIPTION OF THE INVENTION The above and other objectives are achieved by the present invention, which provides a sustained release formulation comprising a therapeutically effective amount of ropinirole or its pharmaceutically acceptable salt in combination with one or more different rate controlling anionic polymeric excipients and optionally a hydrophilic matrix forming agent, the formulation being adapted to release ropinirole in a sustained manner when the formulation is exposed to an environmental fluid. The 'rate controlling polymeric excipient' as used herein is a polymer which is primarily anionic in nature. The said polymer assists in trapping the drug (ropinirole) and releasing it in a sustained manner into the body, particularly the blood plasma. The amount of the said excipient may be about 5 % to 99 %, by weight of the final product. The amount of drug to anionic rate controlling polymeric excipient ratio may be, e.g., from about 1:1 to about 1:500. More preferably, from about 1:10 to about 1:500. The rate controlling polymeric excipient used in the present invention may be selected from an anionic rate controlling polymer or cationic rate controlling polymer cationic ion-exchange resin. The anionic rate controlling polymeric excipient may be present in an amount of 5 to 99 % w/w of the said formulation. Preferably, the amount of anionic rate controlling polymer may be 30 to 99 % w/w of the said formulation. If carrageenan is used in the formulation, it may be in the range of 5 to 95 % w/w of the formulation. The amount of lambda carrageenan or iota carrageenan if used as the rate controlling anionic polymer may be about 5 to 95 % w/w of the formulation. The cationic ion-exchange resin may be present in combination with one or more hydrophilic matrix forming agents such as polymers. The ion-exchange resin may be sodium polystyrene sulfonate present in an amount of 0.5 to 70 % w/w of the formulation. The amount of hydrophilic matrix forming agent may be about 50 to 99 % w/w of said formulation. Preferably, the amount of ion-exchange resin is 2 to 25 % and the concentration hydrophilic matrix forming agent is 50 to 99 %. The hydrophilic matrix forming agent may be a pharmaceutically acceptable biocompatible and/or biodegradable material, including non-cross-linked polyvinylpyrrolidone, hydroxypropylcellulose with a molecular weight of 100,000 to 4,000,000, sodium carboxymethyl cellulose, carboxymethyl starch, potassiummethacrylate-divinylbenzene copolymer, hydroxypropylmethylcellulose of molecular weight between 2,000 and 4,000,000, a polyethyleneglycol of molecular weight between 200 and 15,000, a polyoxyethylene with molecular weight of up to 20,000,000, a carboxyvinylpolymer, a poloxamer (polyoxyethylene-polyoxypropylene copolymer), a polyvinylalcohol, a glucane (glucan), a carrageenan, a scleroglucane (scleroglucan), a mannan, a galactomannan, gellans, xanthans, alginic acid and/or a derivative thereof, polyaminoacids, methyl vinyl ether/maleic anhydride copolymer, carboxymethylcellulose and/or a derivative thereof, ethylcellulose, methylcellulose, starch, a starch derivative, alpha, beta, or gamma cyclodextrin and/or a dextrin or a combination therof. The said matrix forming agent in combination with ion-exchange resin may preferably be selected from amongst or a combination of hydroxypropylmethylcellulose, xanthan gum or carrageenan. Preferably xanthan gum is the hydrophilic matrix forming agent in combination with ion-exchange resin and is present in an amount of 5 to 99% of the said formulation. More, preferably hydroxypropylmethylcellulose is the hydrophilic matrix forming agent in combination with an ion-exchange resin and is present in the concentration range of 50 to 99% of the said formulation. Further, carrageenan may be the hydrophilic matrix forming agent in combination with ion-exchange resin and is present in the concentration range of 50 to 99% of the said formulation. In a preferred embodiment, the formulation comprises sodium polystyrene sulfonate present in combination with xanthan gum and hydroxypropylmethylcellulose wherein the amount of sodium polystyrene sulfonate is 0.5 to 50% w/w, xanthan gum is 5 to 99 % w/w and hydroxypropylmethylcellulose is about 50 to 99% w/w. In yet another embodiment, the formulation comprises sodium polystyrene sulfonate present in combination with carrageenan and hydroxypropylmethylcellulose wherein sodium polystyrene sulfonate is present in an amount of 0.5 to 50%, carrageenan is about 50 to 99 % and hydroxypropylmethylcellulose is about 50 to 99%. The formulation may also comprise sodium polystyrene sulfonate present in combination with a combination of carrageenan and xanthan gum wherein amount of sodium polystyrene sulfonate is 0.5 to 50%, carrageenan is 50 to 99 % and xanthan gum is 5 to 99%. Yet another embodiment is a formulation comprising xanthan gum in combination with carrageenan where in the amount of xanthan gum is in the range of 40 to 99% w/w more preferably 60 to 99% w/w and the amount of carrageenan is 0.5 to 60 % and more preferably 0.5 to 40%. The amount of ropinirole or its pharmaceutically acceptable salt may be present up to 12.0 mg, preferably from 0.1 mg to 12.0 mg, measured as the amount of ropinirole base present, that is excluding any amount of acid (for example, hydrochloric acid) added to form any ropinirole salts. The amount of ropinirole present, inclusive of pharmaceutically acceptable salts thereof, may be up to 12.0 mg, preferably from 0.75mg to 12.0mg, measured as the amount of ropinirole base present, per 150 mg of active layer present. Part or entire quantity of ropinirole may be pre-granulated or mixed with the rate controlling polymers prior to incorporation into the final formulation. Ropinirole may be co-processed at the particle and/or sub particle level with the rate controlling polymers. This may be achieved by spray drying, precipitation with anti solvent, flash evaporation, lyophilization, supercritical fluid processing or any other suitable techniques. Additionally, a formulation wherein ropinirole hydrochloride has been pre-granulated and mixed with the rate controlling polymers can be utilized. Ropinirole hydrochloride may also be co-processed at the particle and/or sub particle level with a lipophilic substance prior to incorporation into the anionic rate controlling polymers. In a still further embodiment of the invention, the said lipophilic substances include a natural fat (for example coconut, soya, cocoa) as such or totally or partially hydrogenated, beeswax, polyethoxylated beeswax, a mono-, bi-or tri-substituted glyceride, glyceryl palmitostearate, glyceryl behenate, diethyleneglycol palmitostearate, a polyethyleneglycol stearate, a polyoxy ethyl enegly col palmitostearate, glyceryl monopalmitostearate, cetyl palmitat, polyethyleneglycol palmitostearate, mono-or di-glyceryl behenate, a fatty alcohol associated with a polyethoxylate fatty alcohol, cetyl alcohol, stearic acid, a saturated or unsaturated fatty acid or a hydrogenated derivative thereof, and/or hydrogenated castor oil. In an embodiment of the invention the system may release the drug at a rate independent of the pH and/or ionic strength of the environment of use. For such a purpose, pH modifiers and/or buffering agents and/or salts may be incorporated into the matrix or by applying an enterosoluble coat to the composition to prevent faster release in acidic environment of use. The formulation of the invention may be can be administered orally in the form of tablets, pills, or the granulate may be directly filled into capsules. The tablets may be prepared by techniques known in the art and contain a therapeutically useful amount of ropinirole and such excipients as are necessary to form the tablet by such techniques. In general, tabletting may be through direct compression, i.e. a mixture of dry powders being compressed, but this can sometimes cause quality issues such as segregation, poor flow etc. These processes may be improved by the use of granulation techniques on all or part of the constituent mix. Granulation is a process in which powder particles are agglomerated together to form granules. This may be carried out to: (i) improve the flow properties of a powder mixture, (ii) prevent segregation of the constituent powders (improve homogeneity), (iii) improve compression characteristics, (iv) achieve densification of powder mixes, and/or (vi) achieve alteration of particle size/shape/hydrophilic properties The tablet of the invention may be prepared by dry granulation. Dry Granulation is granulation by compression of powders by either slugging or roller compaction. It is essentially a densification process. Slugging is where a crude compact (slug) is produced to a set weight/thickness for a given diameter of slug. These slugs are then reduced by either grating or commuting mill to produce granules of the required particle size/range. Roller compaction or Chilsonating is where a powder mix is forced via an auger between 2 rollers (which can be smooth or grooved). Compaction of this material is controlled by the feed rate to the rollers and the hydraulic force of the rollers being pushed together. The resulting compact (called a ribbon or strip) is then reduced by either grating or commuting mill to produce granules of the required particle size/range. The composition of the invention also typically includes pharmaceutically acceptable excipients. Diluents, or fillers, are added in order to increase the mass of an individual dose to a size suitable for tablet compression. Suitable diluents include powdered sugar, calcium phosphate, calcium sulfate, microcrystalline cellulose, lactose, mannitol, kaolin, sodium chloride, dry starch, sorbitol, etc. Lubricants are incorporated into a formulation for a variety of reasons. They reduce friction between the granulation and die wall during compression and ejection. This prevents the granulate from sticking to the tablet punches, facilitates its ejection from the tablet punches, etc. Examples of suitable lubricants include talc, stearic acid, vegetable oil, calcium stearate, zinc stearate, magnesium stearate, etc. Glidants are also typically incorporated into the formulation. A glidant improves the flow characteristics of the granulation. Examples of suitable glidant's include talc, silicon dioxide, and cornstarch. Binders may be incorporated into the formulation. Binders are typically utilized if the manufacture of the dosage form uses a granulation step. Examples of suitable binders include., povidone, polyvinylpyrrolidone, xanthan gum, cellulose gums such as carboxymethylcellulose, methyl cellulose, hydroxypropylmethylcellulose, hydroxycellulose, gelatin, starch, and pregelatinized starch. Other excipients that may be incorporated into the formulation include preservatives, antioxidants, or any other excipient commonly used in the pharmaceutical industry, etc. The amount of excipients used in the formulation will correspond to that typically used in a matrix system. The total amount of excipients, fillers and extenders, etc. varies from about 10 % to about 40 % by weight of the dosage form. Tablets and pills may additionally be prepared with enteric coatings and other release-controlling coatings for the purpose of acid protection, easing swallow ability, etc. The coating may be colored with a pharmaceutically accepted dye. The amount of dye and other excipients in the coating liquid may vary and will not impact the performance of the extended release tablets. The coating liquid generally comprises film forming polymers such as hydroxypropyl cellulose, hydroxypropylmethyl cellulose, cellulose esters or ethers such as cellulose acetate or ethylcellulose, an acrylic polymer or a mixture of polymers. The coating solution is generally an aqueous solution or an organic solvent further comprising propylene glycol, sorbitan monoleate, sorbic acid, fillers such as titanium dioxide, pharmaceutically acceptable dye. A colourant layer or a film of gastroresistant and enterosoluble polymeric material may also be applied to said finished tablets, so as to allow the activation of the system only after the tablet has reached the duodeno-intestinal tract. Pharmaceutical systems of the latter type can be utilised for the accomplishment of tablets specifically designed to release ropinirole in the latter part of the intestinal tract i.e. at colon level. In order to attain gastroresistance, polymeric materials such as cellulose acetophthalate, cellulose acetopropionate, cellulose trimellitate, polymers and acrylic and methacrylic copolymers can be used of different molecular weights and with solubility which depends on different pH values. Said materials can be applied to the finished pharmaceutical form (active layer and the barrier layer (s)) by the classical coating process, utilising solutions in organic solvents or aqueous dispersions and spraying or fiuidised bed nebulisation. Said gastroresistant and enterosoluble materials can likewise be utilized in association with retarder polymers. One innovative embodiment is characterized in that is possible to achieve the claimed therapeutic system by utilizing the production technologies currently in use, i.e. the system may be immediately set up at industrial level. Following examples are provided to further explain the present invention. However, the scope of the present invention should not be limited by these examples. EXAMPLE 1 In Examples 1, sustained release tablets were prepared as set forth below: Table 1 (Table Removed) Processing Steps: 10 kg batch 1. Weigh out ropinirole hydrochloride, xanthan gum, magnesium stearate and colloidal silicone dioxide. 2. Mix ropinirole hydrochloride with xanthan gum. 3. Add magnesium stearate and colloidal silicone dioxide and mix further 4. Compress the mixed powder into tablets using 10 mm round flat punches with a hardness of 7 - 10 kp. EXAMPLE 2 In Example 2, sustained release tablets were prepared as set forth below: Table 2 Example 2 (Table Removed) Processing Steps: 10 kg batch 1. Weigh out ropinirole hydrochloride, xanthan gum, magnesium stearate and colloidal silicone dioxide. 2. Mix ropinirole hydrochloride with xanthan gum. 3. Add magnesium stearate and colloidal silicone dioxide and mix further 4. Compress the mixed powder into tablets using 10 mm round flat punches with a hardness of 7 - 10 kp. EXAMPLE 3 In Example 3, sustained release tablets were prepared as set forth below: Table 3 Example 3 (Table Removed) Processing Steps: 10 kg batch 1. Weigh out ropinirole hydrochloride, xanthan gum, sodium polystyrene sulfonate, hydroxypropylmethylcellulose, magnesium stearate and colloidal silicone dioxide. 2. Mix ropinirole hydrochloride with xanthan gum, sodium polystyrene sulfonate and hydroxypropylmethylcellulose. 3. Add magnesium stearate and colloidal silicone dioxide and mix further 4. Compress the mixed powder into tablets using 10 mm round flat punches with a hardness of 7- 10 kp. EXAMPLE 4 In Example 4, sustained release tablets were prepared as set forth below: Table 4 Example 4 (Table Removed) Processing Steps: 10 kg batch 1. Weigh out ropinirole hydrochloride, xanthan gum, lambda carrageenan, microcrystalline cellulose, hydroxypropylmethylcellulose, magnesium stearate and colloidal silicone dioxide. 2. Mix ropinirole hydrochloride with xanthan gum, lambda carrageenan, microcrystalline cellulose and hydroxypropylmethylcellulose. 3. Add magnesium stearate and colloidal silicone dioxide and mix further 4. Compress the mixed powder into tablets using 10 mm round flat punches with a hardness of 7 - 10 kp. EXAMPLE 5 Dissolution Testing Tablets prepared in accordance with Examples 1 - 4 are tested with respect to in-vitro dissolution. The dissolution tests are conducted in an USP dissolution apparatus (Paddle Type II), and the amount of drug released was analyzed via UV analysis. Results of dissolution studies are summarized in table 5. Table 5 (Table Removed) The Examples provided above are not meant to be exclusive. Many other variations of the present invention will be apparent to those skilled in the art, and are contemplated to be within the scope of the present invention. As shown in table above, the composition prepared as per Example 2 shows the best results as values for zero order kinetics. The release kinetics of the composition containing the drug as prepared in each of the examples is also shown in figures 1-5. It is evident from the figures that the average release profile of the composition of Example 2 is the best. The results have been repeated at least 3 times and found to be reproducible. In the figures, the cumulative percentage drug release has been plotted on the Y-axis and the time take for the release of the drug is plotted on the X-axis. The graph so obtained is ideally expected to be a substantially straight line. Such a straight line is indicative of the fact that the drug is released in a sustained manner from the composition. It would be evident from the figures that the composition of Example 1 exhibits a release profile which is near straight line, the composition of Example 2 is almost as straight line whereas the composition of Examples 3-5 exhibit a straight line and also without any excessive peaks and troughs. The in-vitro dissolution profile of the composition, especially of Example 2 exhibits a profile wherein 16.85 % of drug is released in 1 hour, 32.53 % in 4 hours, 41.02 % in 6 hours, 65.65 % in 12 hours, 79.53 % in 16 hours and 100.00 % in 24 hours. Thus, the release of the drug from the matrix is uniform and is evidence that the composition is a sustained release composition. Ropinirole hydrochloride is a low dose highly water soluble drug. Therefore, preparing a sustained release formulation for such a drug is a challenging task at least for the reason that most commonly used polymeric substances are not suitable for Ropinirole. Further sustained release formulations based on matrix systems are usually unable to provide a constant rate of release and releases rates invariably decline with the passage of time. It is also known that is difficult to control the release of highly soluble and low dose drugs like ropinirole for prolonged period of time by simple formulation approaches. The compositions of the invention disclosed herein is surprisingly able to control the release of ropinirole for prolonged periods of time and also provide a constant near zero order rate of release by incorporation of anionic rate controlling polymers. Some prior art workers such as in US 20040247676 did disclose multi-layered complex systems for controlling the release ropinirole. However, as against such art, the invention provides a simple monolithic system whereby the rate of release of ropinirole may be sustained and controlled. The novelty aspect of the present invention lies in providing a simple, low cost method which requires no specialized machinery and can utilize existing plant machinery, for the manufacture of a sustained release formulation of ropinorole. The formulation differs from existing formulations in the same category, in being monolithic (consisting of a single block and not multiple layers) and also offering the advantage of granulation and thus packaging into capsules, which is not possible in existing formulations utilizing multilayer technology. Infact the inventors tried to use polymeric substances such as hydroxy propyl methyl cellulose, hydroxy propyl cellulose, sodium alginate, and sodium carboxy methyl cellose for preparing the sustained release composition, however, all these compositions were found to be highly ineffective. At least, the following compositions of the prior art were tried and found ineffective. Component (Formula Removed) Infact in some cases, there was an initial burst of the drug or in some cases the drug was released in abrupt or erratic fashion. The same is illustrated graphically by fig. 5 which shows that all the drug is released within less than 30 minutes and thereafter, the peak flattens as there is no more drug to be released. The applicant after a lot of studies found that it is only the composition of the invention that provides the sustained release effect and not any other composition. Yet another advantage is that the formulation provides a zero order release as it is rare for matrix formulations especially simple single component matrices, to exhibit such a release profile. Normally sophisticated systems like osmotic delivery systems or geo-matrix technology are employed to achieve zero order release profile. But the composition has achieved using a very simple matrix table technology. We Claim:- 1. A sustained release monothilic formulation of ropinirole, comprising ropinirole or pharmaceutically acceptable salts thereof formulated with rate controlling anionic polymeric excipients selected from a group comprising of xanthan gum, carrageenan, chitosan and cationic ion-exchange resin or a mixture thereof, wherein the ropinirole and the rate controlling anionic polymeric excipients are in a ratio ranging between 1:1 to 1:500, optionally along with hydrophilic matrix forming agent. 2. A formulation as claimed in claim 1 wherein the ropinirole and the rate controlling anionic polymeric excipients are in a ratio ranging between 1:10 to 1:500. 3. The formulation as claimed in claim 1 wherein the cationic ion-exchange resin is sodium polystyrene sulphonate. 4. A formulation as claimed in claim 1 wherein the hydrophilic matrix forming agent comprise a pharmaceutically acceptable biocompatible and/or biodegradable with a molecular non-cross-linked polyvinylpyrrolidone, hydroxypropylcellulose with a molecular weight of 100, 000 to 4,000,000, sodium carboxymethylcellulose, carboxymethylstarxh, porassiummethactylate-dibinylbenzene copolymer, hydroxypropylmethylcellulose of molecular weight between 2, 000 and 4, 000, 000, a polyethyleneglycol of molecular weight between 200 and 15, 000, a polyoxyethylene with molecular weight of up to 20, 000, 000, a carboxyvinylalcohol, a glucane (glucan), a carrageenan, a sceroglucane (scleroglucan), a mannan, a galactominoacids, methyl vinyl ether/maleic anhydride copolymer, carboxymethylcellulose and/or a derivative thereof, ethylcellulose, methylcellulose, starch, a atarch derivative, alpha, beta, or gamma cyclodextrin and/or a dextrin and more preferably hydroxypropylmethycellulose xanthan gum or carrageeenan; or combination thereof 5. A formulation as claimed in claim 1 wherein the formulation comprises xanthan gum in combination with carrageenan wherein the amount of xanthan gum is in the range of 40 to 99.% w/w more preferably 60 to 99% and the amount of carrageenan is in the range of 0.5 to 60% w/w and more preferably 0.5 to 40%. 6. A formulation as claimed in claim 1 wherein the formulation is a tablet, pellet, granulate and most preferably a tablet which may be additionally coated with a rapidly or slowly soluble or enterosoluble polymer film.

Documents:

2755-DEL-2005-Abstract-(11-04-2012).pdf

2755-del-2005-abstract.pdf

2755-DEL-2005-Claims-(02-07-2012).pdf

2755-DEL-2005-Claims-(11-04-2012).pdf

2755-del-2005-claims.pdf

2755-DEL-2005-Correspondence Others-(02-07-2012).pdf

2755-DEL-2005-Correspondence Others-(11-04-2012).pdf

2755-del-2005-correspondence-others.pdf

2755-del-2005-description (complete).pdf

2755-DEL-2005-Drawings-(11-04-2012).pdf

2755-del-2005-drawings.pdf

2755-del-2005-form-1.pdf

2755-del-2005-form-18.pdf

2755-del-2005-form-2.pdf

2755-DEL-2005-Form-3-(11-04-2012).pdf

2755-del-2005-form-3.pdf

2755-del-2005-form-5.pdf

2755-DEL-2005-GPA-(02-07-2012).pdf

2755-DEL-2005-GPA-(11-04-2012).pdf