Field of invention
The present invention relates to oral liquid compositions of antiparkinson drug. More specifically, the present invention relates to oral liquid compositions comprising Ropinirole and pharmaceutically acceptable salts thereof.
The present invention also relates to process for preparation of oral liquid pharmaceutical compositions.
Background of Invention
Ropinirole is a non-ergoline dopamine agonist, indicated for the treatment of signs and symptoms of idiopathic Parkinson's disease, and for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS).
Chemically, Ropinirole is hydrochloride salt of 4-[2-(dipropylamino) ethyl]-1, 3-dihydro-2H-indol-2-one, and is disclosed and claimed in US 4,452,808. Ropinirole HC1 is a white to pale greenish-yellow powder having a solubility of 133 mg/ml in water. It is sold under the brand name REQUIP® as tablets for oral administration in US and Europe.
The tablet dosage form is generally convenient mode of administering the required dose. But in the case of geriatric patients, particularly suffering with Parkinson's disease, there will be difficulty in holding the tablet and also in swallowing. Therefore, with tablet dosage form patient compliance may be reduced and successful completion of long term therapy may not be possible. Thus, tablet dosage forms may not be most preferable for such patients. Therefore, a liquid dosage form of Ropinirole which is easy to swallow is desirable as this would be expected to improve overall patient compliance. Hence, there exists need for the development of liquid formulations of Ropinirole.

Inventors of the present invention have formulated Ropinirole in the form of stable liquid formulation, which has not been approved earlier, for example, a clear liquid solution for better patient compliance.
Objective of the invention
Accordingly, the main objective of present invention is to provide oral liquid dosage forms of Ropinirole or its pharmaceutically acceptable salts, which are stable during storage.
Yet another objective of the present invention is to provide the proposed liquid product which is stable and bio equivalent to the tablet formulation REQUIP®.
Summary of the invention
According to the main embodiment of the present invention, there is provided stable oral liquid dosage forms of Ropinirole or its pharmaceutically acceptable salts, characterized in that the pH of the dosage form lies in the range of 2.0-6.5.
According to another embodiment of the present invention, there is provided process for preparing oral liquid dosage forms of Ropinirole or its pharmaceutically acceptable salts, characterized in that the pH of the dosage form lies in the range of 2.0 - 6.5.
Detailed description of the invention
In another embodiment of the present invention the oral liquid dosage forms further comprises one or more excipients such as sweeteners, pH adjusting agents, preservatives, buffering systems, antioxidants, chelating

agents, viscosity enhancing agents, flavouring aids, colouring aids and mixtures thereof.
The oral liquid compositions of the present invention may be in the form of solution, elixir or syrup.
Suitable preservatives used according to the present invention are selected from methyl paraben, propyl paraben, alkyl hydroxybenzoates; sorbic acid or a salt thereof; benzoic acid or a salt thereof; and mixtures thereof.
Suitable buffering systems according to the present invention include combinations of citric acid and salts and solvates thereof, for example citric acid (anhydrous or monohydrate) combined with sodium citrate dihydrate.
Suitable antioxidants of the present invention are selected from true antioxidants such as butylated hydroxy toluene (BHT), butylated hydroxy anisole, (BHA), ascorbic acid, cysteine hydrochloride and the like
Suitable chelating agents according to the present invention include edetic acid and their salts.
Suitable viscosity enhancing agents according to the present invention include gums (e.g. Xanthan gum), glycerol, polyvinyl alcohol, polyvinylpyrrolidine, cellulose derivatives, and mixtures thereof.
Suitable flavouring aids according to the present invention include strawberry, cherry, grape, and vanillin flavouring aids.
Suitable sweeteners according to the present invention include glucose, glycerol, fructose, sucrose, lactose, maltose, sorbitol, xylitol, maltitol, erythritol, aspartame, prosweet and the like or mixture thereof.
Suitable liquid carriers according to the present invention include water, alcohol, and mixtures thereof.

The oral liquid compositions of the present invention have a viscosity ranging from 1 to 100 cps, preferably 10 to 75 cps.
The pH of liquid composition lies within the range of 2.0 and 6.5. Inventors of the present invention have found that Ropinirole gets degraded when pH of the composition is below 2.0 and above 7.0.
In yet another embodiment of the present invention, pharmaceutical^ acceptable excipient comprises pH adjusting agents such as amino acids selected from the group consisting of glutamic acid, aspartic acid, cysteine hydrochloride and the like or inorganic acid such as hydrochloric acid.
In yet another embodiment of the present invention, the pharmaceutically acceptable salts of Ropinirole are selected from hydrochloride, hydrobromide, and the like.
In yet another embodiment of the present invention, the concentration of Ropinirole in the composition expressed as free base, lies in the range of 0.001 to 0.5%.
The applicants have found that the use of one or more polyhydric alcohols provides a surprisingly advantageous pharmaceutical composition by virtue of its good stability and acceptable taste.
The present invention also provides for a method of treating a mammal, including man, suffering from signs and symptoms of idiopathic Parkinson's disease, and for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS), which comprises administration of an oral liquid compositions of ropinirole or its pharmaceutically acceptable salts comprising sweetener and pH of the composition lies in the range of 2.0 - 7.0.

According to the main embodiment of the present invention, there is provided stable
The following examples further exemplify the inventions and are not intended to limit the scope of the inventions. It is obvious to those skilled in the art to find out the composition for other dosage forms and substitute the equivalent excipients as described in this specification or with the one known to the industry.
The processing steps involved in making oral liquid dosage disclosed in examples 1-3, are as given below :
(a) dissolved methyl paraben and propyl paraben in water with the aid of
heat, if necessary,
(b) added sorbitol solution and stirred,
(c) dissolved citric acid, sodium citrate, and ropinirole by stirring and added to the solution of step (b),
(d) added flavours and stirred and
(e) made the volume with water, filtered and filled in to the container.
Example 1

We claim:
1. An oral liquid dosage form of Ropinirole or its pharmaceutical^ acceptable salts characterized in that the pH of the dosage form lies in the range of 2.0- 7.0.
2. The liquid dosage form as claimed in claim 1, further comprises one or more excipients selected from sweeteners, pH adjusting agents, preservatives, buffering systems, antioxidants, chelating agents, viscosity enhancing agents, flavouring aids and colouring aids.
3. The liquid dosage form as claimed in claim 1, in the form of solution, elixir or syrup.
4. The liquid dosage form as claimed in claim 1, wherein the sweetener is selected from glucose, glycerol, fructose, sucrose, lactose, maltose, sorbitol, xylitol, maltitol, erythritol, aspartame, prosweet or mixture thereof.
5. The liquid dosage form as claimed in claim 1, wherein the concentration of Ropinirole in the composition expressed as free base, lies in the range of 0.001 to 0.5%.
Dated this 9^ day of £&f>ter*>b£a 2005.
For Aurobindo Pharma Limited