FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
THE PROVISIONAL SPECIFICATION
(See section 10)
1. "PHARMACEUTICAL FORMULATIONS OF NSAIDs FOR PARENTRAL USE".
2. CADILA PHARMACEUTICALS LTD., "CADILA CORPORATE CAMPUS", SARKHEJ-DHOLKA ROAD, BHAT, AHMEDABAD, 382210, GUJARAT, INDIA, AN INDIAN COMPANY.
3. THE FOLLOWING SPECIFICATION DESCRIBES AND ASCERTAINS THE NATURE OF THIS INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED.

Title : PHARMACEUTICAL FORMULATIONS OF NSAIDs FOR PARENTRAL USE

FIELD OF THE INVENTION
The invention relates to clear stable novel formulations comprising of non- steroidal antiinflammatory drug (NSAIDs), for the parenteral use.

BACKGROUND OF THE INVENTION
As a therapeutic class, Nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit analgesic, antiinflammatory, antipyretic, and platelet inhibitory properties. However, these drugs have side effects such as gastrointestinal (GI) toxicities, gastric mucosal ulcerations and hemorrhage due to inhibition of prostaglandin production. The mechanism of action of NSAIDs has been attributed to their ability to inhibit the cyclooxygenase enzyme (cox). Out of the 2 isoforms of cyclooxygenase, cox-1 is responsible for mediating the production of prostaglandin while cox-2 is primarily associated with inflammation, pain, and fever. The traditional NSAIDs are nonselective cox inhibitors. Cox-2 selective NSAIDs are, therefore, ideal anti-inflammatory drugs with minimum drug-related side effects, since they spare cox-1 activity. Meloxicam, which belong to the class of NSAIDs, is used for pain related symptoms in both humans and animals.
Poor solubility and wettability of meloxicam, causes problems in preparation of pharmaceutical formulations, to be administered by the parenteral route. The use of cosolvents has been employed by several workers to solubilize meloxicam. EP-A-0 945 134 discloses pH dependent solubility characteristics of meloxicam and its salts, such as t sodium salt, ammonium salts, and meglumine salts, in the aqueous solution. WO 2005/105101 discloses formulations containing aqueous solutions of meloxicam or meloxicam salt in concentration of 0.1 to 50 mg/ml. To stabilize the formulation it is essential to include additives include pH adjusters, solubilizers, gelling agents, viscosity enhancers, preservatives, oils, antioxidants, emulsifiers, foam-forming agent etc. Surprisingly, it has been possible to produce stable clear aqueous solution of meloxicam salts only. There is no report in which meloxicam as such has been soluble to produce clear stable parenteral solutions. It is a long standing need of the industry to provide clear and stable products in which only meloxicam has been solubilized.

OBJECT OF THE INVENTION
The object of this invention is to provide a clear and stable solution of NSAIDs such as meloxicam for parenteral use without incorporation of any additives.

DESCRIPTION OF THE INVENTION
In the present invention, meloxicam or its salts is added to a solvent and pH is adjusted from 8 to 10. To dissolve the active drug (meloxicam or its salts) the solvent is selected from the family of 2-pyrrolidones (e.g. N-methyl 2-pyrrolidone). The pH is adjusted with the base or acid e.g., sodium hydroxide solution or hydrochloric acid solution. Though preservatives and buffers are not essential to solubilization, these may optionally be used. Excipients used may be from alcoholic group e.g., ethyl alcohol. The formulation was found to be stable even when subjected to the process of final sterilization.
The concentration of meloxicam in the solution may vary from 0.1 mg/ml to 50 mg/ml. The formulation according to the invention overcomes the problem arising from the prior art of providing an injectable solution of the active meloxicam for treating inflammatory conditions, by permitting a low and high concentration without the use of salt form of active substance in a clear and stable solution having the compositions hereinafter. The invention is illustrated using non - limiting examples

EXAMPLES
(1) Preparation of 0.5 % solution of meloxicam
Dissolve 5 g meloxicam in 0.54 liters of N- methyl pyrolidone and stir till a clear solution is formed. Add 0.14 liters of alcohol to the solution and stir for 5 min. Adjust pH with 10 % Sodium hydroxide upto 8.8. Make up the required volume upto one litre with water for injection (WFI) and filter through 0.22 micron nylon filter in sterilized vials. Subject the filled vials to autoclaving at 121° C for 15 mins. The solution kept at various temperature and humidity conditions is stable.
(2) 2 % solution of meloxicam
Dissolve 5 g meloxicam in 0.54 liters of N- methyl pyrolidone and stir till a clear solution is formed. Add 0.14 liters of alcohol to the solution and stir for 5 min. Adjust pH with 10 % Sodium hydroxide upto 8.8. Make up the required volume upto one litre with WFI and filter through 0.22micron nylon filter in sterilized vials. Subject the filled vials to autoclaving at 121°
C for 15 minutes. The solution kept at various temperature and humidity conditions is stable. The examples clearly demonstrate that t is possible to prepare clear and stable solutions of meloxicam & its salts without the use of any additives.