Title of Invention	"NOVEL THERAPEUTIC INJECTABLE ANALGESIC COMPOSITION COMPRISING NIMESULIDE
Abstract	Novel Therapeutic injectable analgesic pharmaceutical compositions for intramuscular administration comprising nimesulide are provided. The pharmaceutical compositions comprise specifically nimesulide 3-7%, dimethylacetamide 5-12%, benzyl benzoate 20 -50%, benzyl alcohol 0 - 10% and ethyl oleate 30 - 65% which provides a rapid absorption and distribution of Nimesulide in body fluids.

Full Text

The present invention relates to Novel Therapeutic Injectable Analgesic Composition containing Nimesulide which is N-(4-nitro, 2-phenoxyphenyl) methanesulfonamide, for intramuscular administration. The use of Nimesulide through intra-muscular administration as an analgesic agent has not been successful because Nimesulide being practically insoluble in water and its formulations in conventional oily bases or as suspensions result in depot formation in the muscular tissues which defies the main objective of quick relief. The market and literature survey shows that no parenteral dosage form of Nimesulide is reported. (Drugs, 48 (3) 431-454, 1994). An injectable formulation of nimesulide has been reported in the prior art (PCT Patent No. WO 95/34533) which utilizes a salt form of nimesulide (nimesulide-L-lysine) complexed with cyclodextrins. The maximum solubility achieved was reported to be 2.4 mg/ml, which is not suitable for an intramuscular injection as it would require very large volumes to administer therapeutic doses. The reported oral dose of nimesulide ranges between 100 to 400 mg per day. Contemplating that the intramuscular dose is half of the oral dose, 50 mg of the drug needs to be injected which would require approximately 20 ml of the solution described in the prior art. See WO 95/34533. Whereas the maximum solubility achieved in the said composition is 50 mg/ml of nimesulide which is the effective dose required for intra muscular administration. It is an object of the present invention to provide a Novel Therapeutic Injectable Analgesic Composition containing Nimesulide for intramuscular administration from which the Nimesulide is rapidly absorbed and distributed in body fluids. Accordingly, the present invention provides a Novel Therapeutic Injectable Analgesic Composition for intra-muscular administration comprising the following ingredients: Nimesulide : 3% to 7% w/v Dimethylacetamide : 5% to 12% w/v Benzyl benzoate : 20% to 50% w/v Benzyl alcohol : 0% to 10% w/v Ethyl oleate : 30% to 65% w/v According to a preferred embodiment of the present invention, the therapeutic Injectable analgesic composition, according to the present invention, comprises the following ingredients: Nimesulide : 5% w/v Dimethylacetamide : 10% w/v Benzyl benzoate : 40% w/v Benzyl alcohol : 2% w/v Ethyl oleate : 43% w/v According to another preferred embodiment of the present invention, the Benzyl benzoate used is replaced in part by 5% to 10% w/v of polyoxyl 35 castor oil. According to another preferred embodiment of the present invention, a conventionally known anti-oxidant such as ascorbyl palmitate, butyl hydroxy anisole, butyl hydroxy toluene, propyl gallate and a-tocopherol is added to the said Injectable analgesic composition. The Injectable Analgesic Composition, according to the present invention, is prepared by a process comprising the following steps: (a) 5% to 12% w/v of Dimethylacetamide and 20% to 50% w/v of Benzyl benzoate are mixed in a container fitted with a stirrer at slow speed (1000-1500 rpm) and to that 3% to 7% w/v of Nimesulide is added and stirred till completely dissolved, (b) 0% to 10% w/v of Benzyl alcohol and a portion of 30% to 65% w/v of Ethyl oleate are mixed in a container fitted with a stirrer, (c) the mixture obtained in step (a) is added to the mixture obtained in step (b) under slow stirring and the volume of the mixture obtained is made up to 100 ml by the rest of the amount of ethyl oleate resulting in the preparation of the desired injectable analgesic Composition. Preferably the step (c) of the aforesaid process is carried out under continuous nitrogen flushing and the solution thus obtained is passed through 0.22 m nylon membrane filter. The present invention is examplified by the following examples for the preparation of the Injectable Analgesic composition. EXAMPLE -1 (a) Mix 10 g of Dimethylacetamide and 40 g of Benzyl benzoate in a container fitted with a stirrer at slow speed (1000-1200 rpm) at a temperature between 25.degree.-30.degree. C. Add 5 g of Nimesulide in small increments and stir until completely dissolved. (b) Mix 10 g of Cremophor EL and an amount of Ethyl oleate in a container fitted with a stirrer at room temperature. (c) Add the mixture obtained in step (a) to the mixture obtained in step (b) under slow stirring and stir for about 30 minutes. Make the volume up to 100 ml with Ethyl oleate and filter through 0.22 u nylon membrane filter to make it sterile. EXAMPLE - II (a) Mix 20 g of Dimethylacetamide and 76 g of Benzyl benzoate in a container fitted with a stirrer at slow speed at a temperature between 25° - 30°C. Add to the mixture obtained 10 g of Nimesulide in small amounts at a time and stir until completely dissolved. (b) Mix 4 g of Benzyl alcohol and an amount of Ethyl oleate in a container fitted with a stirrer at room temperature. (c) Add the mixture obtained in step (a) to the mixture obtained in step (b) under slow stirring and stir for about 30 minutes. Make up the volume up to 200 ml with Ethyl oleate and filter through 0.22 jj. nylon membrane filter to make it sterile. The injectable analgesic composition, according to the present invention, on preliminary animal and preclinical trials has shown to possess marked analgesic activity. Further, it has been found to be non-toxic even on repeated applications on the same site. No incidence of tissue necrosis or any other side effect was observed. The analgesic dose ranges from 0.16 mg/kg to 8.4 mg/kg. This analgesic composition is very effective and useful for the treatment of acute painful conditions like-post operative trauma, pain associated with cancer, sports injuries and the like. The analgesic activity of the therapeutic composition, according to the present invention, was found to be dose dependent and passed the tests of subacute toxicity and undue toxicity. The therapeutic Injectable Analgesic Composition, according to the present invention, is not a mere admixture but has properties different from the sum total of the properties of its ingredients, as stated herein above. Since many apparently different embodiments of the present invention could be made without departing from the spirit and scope thereof, it is intended that the description of the invention herein be interpreted as being illustrated only and not limiting in any manner whatsoever. We claim : 1. A Novel Therapeutic Injectable Analgesic Composition for Intra-muscular administration comprises: Nimesulide 3% to 7% w/v Dimethylacetamide 5% to 12% w/v Benzyl benzoate 20% to 50% w/v Benzyl alcohol 0% to 10% w/v Ethyl oleate 30% to 65% w/v 2. A Therapeutic Composition as claimed in claim 1 which preferably comprises: Nimesulide 5% w/v Dimethylacetamide 10% w/v Benzyl benzoate 40% w/v Benzyl alcohol 2% w/v Ethyl oleate 43% w/v 3. A Therapeutic composition as claimed in claims 1 to 2 wherein an anti-oxidant is added to the composition. 4. A Novel Therapeutic Injectable Analgesic Composition substantially as herein described and exemplified in the examples.

Documents:

2047-del-1995-abstract.pdf

2047-del-1995-claims.pdf

2047-del-1995-complete specification (granted).pdf

2047-del-1995-correspondence-others.pdf

2047-del-1995-correspondence-po.pdf

2047-del-1995-description (complete).pdf

2047-del-1995-form-1.pdf

2047-del-1995-form-13.pdf

2047-del-1995-form-19.pdf

2047-del-1995-form-2.pdf

2047-del-1995-form-29.pdf

2047-del-1995-form-3.pdf

2047-del-1995-gpa.pdf

2047-del-1995-petition-137.pdf