Page 1 of 23

FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
TITLE OF THE INVENTION:
NOVEL INJECTABLE COMPOSITION OF DICLOFENAC SODIUM
APPLICANT:
(a) Name: M/S UMEDICA LABORATORIES PVT. LTD
(b) Nationality: Indian
(c) Address: 105/108, Rewa Chambers, 1st Floor, 31, New Marine Lines, Mumbai Maharashtra 400020, India

PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed. Page 2 of 23

NOVEL INJECTABLE COMPOSITION OF DICLOFENAC SODIUM
FIELD OF THE INVENTION:
The present invention relates to injectable preparation of diclofenac and water solubles salts thereof which can be administered via intradeltoid route along with 5 intragluteal, subcutaneous and slow intravenous route. The invention further provides a process of preparing said preparation and its use in treatment of acute or chronic pain & inflammatory conditions.
BACKGROUND OF THE INVENTION:
Diclofenac belongs to a class of non-steroidal anti -inflammatory drugs (NSAIDs) 10 with antipyretic and analgesic properties. NSAIDs are usually indicated for the treatment of acute or chronic pain and inflammatory conditions. Similar to other NSAIDS, diclofenac is generally indicated for rheumatoid arthritis, osteoarthritis, Dysmenorrhea (menstrual pain), Headache and migraine, Postoperative pain and also for mild to moderate pain after tissue injury. It has also been used in some 15 countries for the management of actinic keratosis and fever. Eye drops of Diclofenac Sodium are used for the prevention of intra-operative miosis during cataract extraction, for the treatment of inflammation after surgery or accidental trauma, and for the relief of ocular signs and symptoms of seasonal allergic conjunctivitis. 20
Diclofenac can be administered by oral as well as by parenteral route. Oral doses of diclofenac range from 100-200mg/day while parenteral doses range from 75 to 150mg/day.
Modified-release preparations of Diclofenac Sodium are available for oral use. Diclofenac has also been given in equivalent oral doses as the free acid in tablet 25 forms as dispersible preparations for short-term treatment up to 3 months period. Diclofenac is also given orally as the potassium salt. Page 3 of 23

Diclofenac Sodium may also be given by deep intramuscular injection into the gluteal muscle in a dose of 75 mg once daily or, if required in severe conditions, 75 mg twice daily. Diclofenac Sodium may also be given as a continuous or intermittent intravenous infusion in glucose. 5% or sodium chloride 0.9% (both previously buffered with sodium bicarbonate) or as a bolus intravenous injection. 5 For the treatment of postoperative pain a dose of 75 mg may be given over 30 to 120 minutes or as a bolus injection. The dose may be repeated once after 4 to 6 hours if necessary. To prevent postoperative pain, as initial dose of 25 to 50 mg Diclofenac sodium may be given after surgery over 15 to 60 minutes followed by 5 mg / hour to a maximum of 150 mg daily. Alternatively, the initial dose may be 10 given as a bolus injection over 5 to 60 seconds followed by additional injections up to the maximum daily dosage; this may be repeated after 4 to 6 hours if necessary although the total dose should not exceed the maximum daily dose of 150 mg. The maximum period recommended for parenteral use is 2 days. Diclofenac Sodium is also used intramuscularly in renal colic in a dose of 75 mg 15 repeated once after 30 minutes if necessary.
Diclofenac injections have to be administered deep intramuscularly and are generally administered intraguluteally as the injection causes substantial pain at the site of injection and its administration in the deltoid (upper arm) region is generally avoided. 20
Pain at the site of injection is due to relatively large volume of the injection (3 mL) and the fact that the injection solution contains relatively high volumes of propylene glycol, which is a known irritant upon parenteral administration. As mentioned in Applied Nursing Research, Vol. 16, No. 2, August, 2002 empirical data from published research reports, recommendations of established advisory 25 panels and generally accepted scientific principals conclude that only small volumes of medication (2 ml or less) should be given in the deltoid site.
On the other hand intramuscular injection volumes above 2 ml and up to 5 ml must be administered into the gluteal muscle. This is because; the gluteal muscle Page 4 of 23

is larger as compared to the deltoid muscle and hence can accommodate the relatively larger injected volume (3-5 ml). On the other hand if this relatively larger volume is injected into the deltoid muscle, which has relatively lesser muscle mass, the injected solution will cause excessive stretching of the muscle fiber, thereby damaging the local muscle tissue and hence cause pain and 5 discomfort to the patient.
Commercially available VOLTAROL® ampoules comprise 75mg/3ml solution of Diclofenac sodium which is used as Intra muscular injection. The formulation must be diluted with 100-500ml of either sodium chloride solution (0.9%) or glucose solution (5%) buffered with sodium bicarbonate solution (0.5ml 8.4% or 10 1ml 4.2%) so that only clear solutions are used as intravenous infusion. The sodium metabi sulphite present in solution for injection can also lead to isolated severe hypersensitivity reactions and bronchospasm.
Similarly, another marketed product DYLOJECT® is 75mg/2ml solution for injection of diclofenac sodium. It can be given as intravenous bolus injection for 15 the treatment or prevention of post-operative pain in supervised healthcare system or as an intramuscular injection for the treatment of acute pain and inflammatory conditions. It cannot be given as IV infusion. It is HP-beta-cyclodextrin complex and contains monothioglycerol as antioxidant. These products Dyloject and Voltarol cause thrombophlebitis in 5.4% and 4.9% patients respectively. 20
Further, the high pH of the marketed Diclofenac product requires rendering Diclofenac sodium soluble and the hyper-osmolar nature of the formulation contribute to the discomfort which is frequently experienced at the site of the injection when administered intramuscularly.
Further, injectable Diclofenac preparations contain relatively high amounts (18-25 40%) of propylene glycol, which is known irritant. Page 5 of 23

US Patent No.3558690 discloses injectable preparations comprising water soluble salts of substituted phenyl acetic acid derivatives (diclofenac being one such compound) in concentrations of 0.5 to 5 %.
PCT application number WO 9603121 Al describes a antiphlogistic, analgesic, antipyretic parenteral preparation comprising diclofenac, its salt, or both, a 5 surfactant, co-surfactant, water, at pH of 3-10 and optionally comprising an oily component, that can exhibit sustained therapeutic levels of diclofenac in plasma and which does not cause pain at site of injection.
US5389681 discloses to a pharmaceutical composition in the form of a sterilizable parenteral solution comprising a diclofenac salt and stabilizers, such as ethyl 10 lactate combined with glutathione or N- acetylcysteine. The invention describes a method for treating pain, inflammation or rheumatic diseases.
US555465 discloses an antiphlogistic, analgesic, antipyretic parenteral preparation comprising diclofenac, its salt, or both, a surfactant, and co-surfactant, and water, and having a pH of 3-10 is provided. 15
EP0658347A2 covers a method of preparing an injectable pharmaceutical or veterinary composition which comprises either diclofenac or a salt thereof and 2-hydroxypropyl beta-cyclodextrin, or an inclusion complex of diclofenac or a salt thereof and 2-hydroxypropyl beta-cyclodextrin, includes the step of dissolving either the diclofenac or salt thereof and the 2-hydroxypropyl beta-cyclodextrin, or 20 the inclusion complex, in water to form a solution, the water having been acidified to a pH such that the pH of the solution is from 6.0 to 8.5 inclusive, in the absence of a phosphate buffer.
US2005/0238674 relates to a stable parenteral aqueous solutions comprising either (a) diclofenac or a pharmaceutically acceptable diclofenac salt and a 25 cyclodextrin, or (b) an inclusion complex of diclofenac or a pharmaceutically acceptable diclofenac salt and a cyclodextrin, or a mixture of (a) and (b), which are suitable for intramuscular and intravenous administration. The solutions Page 6 of 23

contain diclofenac or diclofenac salt, cyclodextrin, and an antioxidant selected from monothioglycerol, or a combination of ethylene-diamine tetra-acetic acid and N-acetyl-cysteine. According to the invention, the parenteral solution is in the form of a unit dose that does not exceed 2 milliliters. The stabilized injectable solution of the invention may be intravenously administered by admixture with 5 non-dextrose infusion fluids.
US2011/0275717 discloses a pharmaceutical formulation comprising a pharmaceutically acceptable salt of Diclofenac, at least one polyoxyalkylene ester of a hydroxyl fatty acid, water, and, optionally, a co- solvent. This composition has a limitation with use of fatty acid derivative and requires special carriers. 10
US5679660 teaches about the method of preparing an injectable pharmaceutical or veterinary composition which comprises either Diclofenac or a salt thereof and 2-hydroxypropyl beta-cyclodextrin, or an inclusion complex of Diclofenac or a salt thereof and 2-hydroxypropyl beta-cyclodextrin with preferred' concentration of Diclofenac of 25 mg/ml. The volume of injection prepared by this method 15 contains 75mg/3ml Diclofenac which can be painful as IM dosage form. The use of beta cyclodextrin has also toxicity problem which is always questioned for IV administration.
US20080153914 discloses injectable formulations of water-soluble salts of diclofenac in Glycofurol. However, Glycofurol is known as a tissue irritant. 20
US 4,614,741 teaches about the depot injectable containing anti-inflammatory agents like Diclofenac or Diclofenac Sodium, which was prepared in 10-60% of suspending agents selected from the group consisting of biscoleo, isopropyl myristate, ethyl oleate, castor oil, sesame oil, arachis oil, cottonseed oil, almond oil, olive oil, neats foot oil, neutral oil and maize oil, for intramuscular 25 administration. However, use of such suspending agent provides painful and viscous injection that causes swelling or pain at the site of injection. Page 7 of 23

US 4,711,906 discloses an aqueous, stable, relatively concentrated solution of Diclofenac, which contain a mixture of propylene glycol and polyethylene glycol in defined quantitative proportions. The solutions preferably contain a local anesthetic such as lidocaine and a reducing agent as stabilizer. However, use of propylene glycol makes the injection painful and lignocaine is added to alleviate 5 such painful administration.
The present invention attempts to provide preparations comprising 75mg of water soluble salt of diclofenac & reducing the volume of injection to 1ml resulting in the minimization of pain at site of injection. Further, smaller volume enables administration in the deltoid muscle. 10
Further, inventors find out simple & economical process for the preparation, using cheaper excipients.
OBJECTS OF THE INVENTION:
It is an objective of invention to provide an injectable composition comprising therapeutically effective amount of diclofenac or water soluble salts thereof, in a 15 solvent system comprising two or more solubilizers and water.
Another objective of invention is to provide a therapeutic effective dose of 75mg of water soluble salts of diclofenac in just one ml, without significantly raising the viscosity of the injection preparation. Another objective of invention is to provide a composition comprising diclofenac suitable to be given through multiple routes 20 viz., intramuscular or intravenous or subcutaneous, intradeltoid or intragluteal route of administration.
Another objective of invention is to provide patient compliant aqueous composition of diclofenac which is not irritating or painful.
Another objective of invention is to provide simple & economical process for the 25 preparation. Page 8 of 23

Still another object of the invention is to provide an economical and physiologically effective composition comprising diclofenac or water soluble salts thereof.
SUMMARY OF THE INVENTION:
In an embodiment, the present invention provides an injectable preparation 5 comprising 75mg/ml to 100 mg/ml of diclofenac sodium or therapeutically equivalent amounts of water soluble salts of diclofenac in a solvent system comprising two or more solublizers in an amount ranging from 0.01 to 40% w/v and water and optionally, one or more antioxidant (s) in an amount ranging from 0.01 to 0.5% w/v and/or one or more buffering agent (s) in an amount ranging 10 from 0.05 to 1.0% w/v, wherein the pH of the preparation is maintained at 8-9.
In one embodiment, the invention provides an injectable preparation comprising 75 mg/ml of diclofenac sodium in a solvent system comprising hydroxypropyl-beta-cyclodextrin and polysorbate 80 as solublizers and water.
In another embodiment, the water soluble salts of diclofenac are selected from the 15 group consisting of diclofenac potassium, diclofenac diethyllamine, diclofenac diethanol amine and diclofenac beta-dimethyl aminoethanol.
In another embodiment, the amount of two or more solublizers in the preparation is between 0.01 to 40% w/v. The solublizers may be selected from, but not limited to hydroxypropyl-beta-cyclodextrin, polysorbate 80, Cremophor EL, glycofurol, 20 benzyl alcohol, polyethylene glycol, Cremophor RH 40 and hydrogenated soy phosphatidylcholine.
In another embodiment, the amount of antioxidant (s) in the composition is between 0.01 to 0.5% w/v. The antioxidant (s) may be selected from, but not limited to monothioglycerol, sodium bisulphate and sodium metabisulphate. 25 Page 9 of 23

In another embodiment, the amount of the buffering agent is between 0.05 to 1.0% w/v. The buffering agent (s) may be selected from, but not limited to potassium dihydrogen phosphate, phosphate buffer and bicarbonate buffer.
In another embodiment, the solvent system comprises hydroxypropyl-beta-cyclodextrin in an amount ranging from 0.01 to 40% w/v, polysorbate 80 in an 5 amount ranging from 0.10 to 0.5% w/v and water, and potassium dihydrogen phosphate in an amount ranging from 0.05 to 1.0 % w/v.
In another embodiment, the invention provides a method for preparation of injectable preparation comprises suspending 75mg diclofenac sodium or water soluble salt of diclofenac in the solvent system comprising two or more 10 solubilizers in water for injection, with stirring under constant nitrogen purging, optionally, adding one or more buffering agent (s) and/or antioxidant (s), adjusting pH between 8-9 using an alkali, further diluting with water for injection to achieve concentration of 75mg in 1 ml, sterilizing by sterile filtration and filling in 1 ml ampoules flushed with inert gas prior to sealing. 15
In still another embodiment, the invention provides use of composition comprising 75 mg/ml of diclofenac sodium or water soluble salts of diclofenac in a solvent system comprising two or more solublizers 0.01 to 40% w/v and water and optionally, one or more antioxidant (s) 0.10 to 0.5% w/v and/or buffering agent 0.05 to 1.0 % w/v for treatment or prevention of acute or chronic pain and 20 inflammatory conditions selected from rheumatoid arthritis, osteoarthritis, dysmenorrhea (menstrual pain), headache and migraine, postoperative pain and also for mild to moderate pain after tissue injury, ankylosing spondylitis, pain control of total hip replacement arthroplasty, actinic keratosis and fever, accidental trauma. 25
The details of one or more embodiments of the inventions are set forth in the description below. Other features, objects and advantages of the inventions will be apparent from the description and claims. Page 10 of 23

DETAILED DESCRIPTION OF THE INVENTION:
The "composition" or "formulation" as used herein refers to parenteral preparations include injections, intravenous infusions, powders for injections or intravenous infusions, concentrates for injections or intravenous infusions, implants. 5
The "buffering agent" as used herein refers to either a weak acid or weak base. Buffering agents are usually added to water to form a buffer solution, which only slightly changes its pH in response to other acids and bases being combined with it, particularly a strong acid or a strong base.
The "antioxidant" as used herein refers to substance that inhibits the oxidation of 10 other substances. They are widely used to prevent the oxidative degradation of product.
"pharmaceutically acceptable" is meant those salts and esters which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response 15 and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use.
The invention provides a composition comprising Diclofenac or salt thereof. Diclofenac salt is selected from Diclofenac sodium, Diclofenac potassium, Diclofenac diethylamine, Diclofenac diethanolamine or Diclofenac beta-dimethyl 20 aminoethanol.
Poor aqueous solubility of the Sodium salt of Diclofenac has a particularly high tendency to crystallize from aqueous and organic solutions. The invention provides therapeutically effective amount of Diclofenac or salts thereof in an aqueous composition suitable to be administered by multiple routes. 25 Page 11 of 23

In some embodiments, the invention provides compositions comprising additional excipients e.g. buffering agents, solubilizers and antioxidants.
In another embodiment, the composition comprises solubilizers at a concentration in the range of 0.01 to 40%.
Preferably, the Solubilizers include but not limited to hydroxypropylbetadex 5 (Hydroxypropyl-beta- cyclodextrin), polysorbate 80 (Tween 80), Cremophor EL, glycofurol, acetic acid, N[3- hydroxyethyllactamide, benzyl alcohol, polyethylene glycol, Cremophor RH 40, d-alpha-tocopherol polyethylene glycol 1000 succinate, sulfobutylether-beta-cyclodextrin, L-alpha- dimyristoylphosphatidylglycerol, hydrogenated soy phosphatidylcholine. 10
Preferably, the antioxidant includes but not limited to monothioglycerol, thioglycerols, acetyl cysteine, sodium bisulphate, sodium metabisulphate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ascorbates, ascorbylpalmitate, methylparaben, propylparaben, thiomersal and mixed Tocopherol ingredient. 15
In another embodiment, the invention provides composition comprising the solvent system consisting of hydroxypropyl-beta-cyclodextrin, 0.01 to 40% w/v, polysorbate 80, 0.10 to 0.5% w/v and water, and potassium dihydrogen phosphate, 0.05 to 1.0 % w/v.
In another embodiment, the invention provides method of use of an injectable 20 composition comprising Diclofenac or water soluble salts thereof 75mg for treatment or prevention of various musculoskeletal and joint disorders like rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, peri-articular disorders like bursitis and tendinitis, soft tissue disorders like sprains and strains, painful condition such as renal colic, acute gout, dysmenorrhoea, migraine and some 25 surgical procedures, in management of actinic keratosis and fever, postoperative pain, juvenile idiopathic arthritis, acute postoperative pain, intra-operative miosis, Page 12 of 23

for treatment of inflammation after surgery, pain control of total hip replacement arthroplasty.
The pH is critical for maintaining stability of the Diclofenac injection hence pH is maintained at 8 to 9 using suitable buffering agents and alkalizer. The buffering agents may be selected from, but not limited to alkali metal hydroxides like 5 sodium hydroxide, potassium hydroxide, tri sodium citrate, sodium phosphate salts like monosodium phosphate salt or disodium phosphate salt, potassium phosphate salts like mono or di potassium phosphate salt, sodium acetate, potassium dihydrogen phosphate, phosphate buffer, bicarbonate buffer, Tris buffers or other alkaliser are used for adjusting pH in the desired range. 10
Water is added in the composition in quantity sufficient (q.s.) to make it 0.5 ml or 1 ml or to give different volumes for different strength. The injectable composition may be filled in ampoule and vials after aseptic filtration and flushed under nitrogen blanket. The injections so formed are stable and may diluted further in infusion liquid to obtain the desired strength of drug or without diluting 15 further by intramuscular and as slow bolus intravenous or suitably adding to infusion liquid as per physician need.
In another embodiment, the invention provides a process for preparing composition comprising 75mg of diclofenac sodium or therapeutically equivalent amounts of water soluble salts of diclofenac comprising suspending diclofenac 20 sodium or water soluble salt of diclofenac in the solvent system comprising two or more solubilizers in water for injection, with stirring under constant nitrogen purging, optionally, adding said one or more buffering agent (s) and/or antioxidant (s); adjusting pH between 8-9 using an alkali; further diluting with water for injection to achieve concentration of 75mg in 1 ml; sterilizing by sterile 25 filtration and filling in 1 ml ampoules flushed with inert gas prior to sealing.
Preferably, the invention provides a process for preparing composition comprising 75mg of diclofenac sodium or therapeutically equivalent amounts of water soluble Page 13 of 23

salts of diclofenac comprising suspending diclofenac sodium or water soluble salt of diclofenacin the solvent system comprising hydroxypropyl- beta-cyclodextrin and polysorbate 80 in water for injection, with stirring under constant nitrogen purging, adding potassium dihydrogen phosphate, adjusting pH between 8-9 using an alkali, further diluting with water for injection to achieve concentration of 5 75mg in 1 ml, sterilizing by sterile filtration and filling in 1 ml ampoules flushed with inert gas prior to sealing.
The present invention is further illustrated by the following examples which are provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled 10 in the art and are included within the scope of the present invention. Page 14 of 23

Example 1
Manufacturing Procedure:
Dissolve polysorbate 80 about 0.03%w/v in water for injection (about 50%) under stirring and nitrogen purging, stir till it dissolved in water for injection. Add 5 hydroxypropyl-beta-cyclodextrin about 33.30% w/v to it under stirring and continue stirring till it dissolved. Add diclofenac sodium about 7.50% w/v to polysorbate 80 and hydroxypropyl- -cyclodextrin solution under stirring and continue stirring for about 30 minutes. Add 1% Sodium hydroxide solution to diclofenac sodium dispersion under stirring and continue stirring till clear solution 10 is formed. Check the pH of solution and adjust it to 8-9 if required with 1% Sodium hydroxide solution. Record the quantity of sodium hydroxide solution used for pH adjustment. Make up the volume to 1 mL with water for injection and stir it. Filter the solution through 0.45 micron membrane filter and then through 0.22 micron membrane filter and again check the pH of filtered solution. Carry 15 out filling of the solutions in clear glass ampoules followed by sealing. Page 15 of 23

Example 2
Manufacturing Procedure:
Dissolve hydroxypropylbeta-cyclodextrin about 33.30% w/v in water for injection (about 50%) under stirring and nitrogen purging, stir till it dissolved in water for 5 injection, followed by addition of Monothioglycerol about 0.50% w/v and continue stirring. Adjust the pH of the solution to 4.6 (± 0.5) with 0.1N Hydrochloric acid. Add diclofenac sodium about 7.50% w/v to hydroxypropylbeta- cyclodextrin and monothioglycerol solution under stirring and continue stirring for about 30 minutes. 10
Add polysorbate 80 (Tween 80) about 0.30% w/v in water for injection (about 1%) under stirring and nitrogen purging, stir till it dissolved in water for injection and then add to above diclofenac sodium dispersion. Check the pH of solution and adjust it to 8-9 with 1% Sodium hydroxide solution. Record the quantity of sodium hydroxide solution used for pH adjustment. 15 Page 16 of 23

Make up the volume to 1 mL with water for injection and stir it. Filter the solution through 0.45 micron membrane filter and then through 0.22 micron membrane filter and again check the pH of filtered solution. Carry out filling of the solutions in clear glass ampoules followed by sealing.
5 Page 17 of 23

Example 3
Manufacturing Procedure:
Dissolve polysorbate 80 about 0.03% w/v in water for injection (about 50%) under stirring and nitrogen purging, stir till it dissolved in water for injection. Add 5 hydroxypropyl beta-cyclodextrin about 35.00% w/v to it under stirring and continue stirring till it dissolved. Add diclofenac sodium about 7.50% w/v to hydroxypropyl beta-cyclodextrin and polysorbate 80 solution under stirring and continue stirring for about 30 minutes. Take water for injection (about 20%) and dissolve sodium hydroxide pellets in it under stirring. Then add potassium 10 dihydrogenphosphate about 0.34% w/v under stirring and continue stirring till it dissolved. Check the pH of the solution (limit 8-9). Add buffer solution to diclofenac sodium dispersion under stirring. Continue stirring till all the drug particles get dissolved. Check the pH of solution and adjust it to 8-9 if required with 1% Sodium hydroxide solution. Record the quantity of sodium hydroxide 15 solution used for pH adjustment. Make up the volume to 1 mL with water for injection and stir it. Filter the solution through 0.45 micron membrane filter and Page 18 of 23

then through 0.22 micron membrane filter and again check the pH of filtered solution. Carry out filling of the solutions in clear glass ampoules followed by sealing. Page 19 of 23

We claim:
1. An injectable preparation comprising 75mg/ml to 100 mg/ml of diclofenac sodium or therapeutically equivalent amounts of water soluble salts of diclofenac in a solvent system comprising two or more solubilizers in an amount ranging from 0.01 to 40% w/v and water and optionally one or 5 more antioxidant(s) in an amount ranging from 0.10 to 0.5% w/v and/or one or more buffering agent (s) in an amount ranging from 0.05 to 1.0% w/v, wherein the pH of the preparation is maintained at 8-9.

2. An injectable preparation comprising 75 mg/ml of diclofenac sodium or 10 therapeutically equivalent amounts of water soluble salts of diclofenac in a solvent system comprising two or more solublizers in an amount ranging from 0.01 to 40% w/v and water and optionally, one or more antioxidant (s) in an amount ranging from 0.01 to 0.5% w/v and/or one or more buffering agent (s) in an amount ranging from 0.05 to 1.0% w/v, wherein 15 the pH of the preparation is maintained at 8-9.

3. The injectable preparation according to claims 1-2, wherein the water soluble salts of diclofenac are selected from the group consisting of diclofenac potassium, diclofenac diethyllamine, diclofenac diethanol 20 amine and diclofenac beta-dimethyl aminoethanol.

4. The injectable preparation according to claims 1-2, wherein the solubilizers are selected from the group consisting of hydroxypropyl-beta-cyclodextrin, polysorbate 80, Cremophor EL, glycofurol, benzyl alcohol, 25 polyethylene glycol, Cremophor RH 40 and hydrogenated soy phosphatidylcholine.

5. The injectable preparation according to claim 4, wherein the solubilizers are selected from the group consisting of hydroxypropyl-beta-cyclodextrin 30 and polysorbate 80.
Page 20 of 23

6. The injectable preparation according to claims 1-2, wherein the antioxidant is selected from the group consisting of monothioglycerol, sodium bisulphate and sodium metabisulphate.

7. The injectable preparation according to claims 1-2, wherein the buffering 5 agent is selected from the group consisting of potassium dihydrogen phosphate, phosphate buffer and bicarbonate buffer.

8. The injectable preparation according to claims 1-2, wherein the solvent system comprises hydroxypropyl-beta-cyclodextrin in an amount ranging 10 from 0.01 to 40% w/v, polysorbate 80 in an amount ranging from 0.10 to 0.5% w/v and water and optionally monothioglycerol in an amount ranging from 0.10 to 0.5% w/v and/or potassium dihydrogen phosphate in an amount ranging from 0.05 to 1.0% w/v, wherein the pH of the preparation is maintained at 8-9. 15

9. The injectable preparation according to claims 1-2, wherein the preparation is administered in a route selected from the group consisting of intramuscular, intravenous, intradeltoid and intragluteal route.

20
10. The injectable preparation according to claims 1-2, wherein the solvent system comprises hydroxypropyl-beta-cyclodextrin in an amount ranging from 0.01 to 40% w/v, polysorbate 80 in an amount ranging from 0.10 to 0.5% w/v, water, and potassium dihydrogen phosphate in an amount ranging from 0.05 to 1.0 % w/v, wherein the pH of the preparation is 25 maintained at 8-9.

11. The injectable preparation according to claims 1-2, wherein total volume of the preparation comprises about 1 ml.

30 Page 21 of 23

12. A process for the preparation of 1 ml injectable preparation consisting of 75mg of diclofenac sodium or therapeutically equivalent amounts of water soluble salts of diclofenac according to claim 11, comprising the steps of :

a) suspending said diclofenac sodium or said water soluble salt of diclofenac in the solvent system comprising said two or more solubilizers 5 in water for injection, with stirring under constant nitrogen purging,
b) optionally adding said one or more buffering agent (s) and/or antioxidant (s),
c) adjusting pH between 8-9 using an alkali,
d) further diluting with water for injection to achieve concentration of 10 75mg in 1 ml,
e) sterilizing by sterile filtration and filling in 1 ml ampoules flushed with inert gas prior to sealing.
13. A process for the preparation of 1 ml injectable preparation consisting of 15 75mg of diclofenac sodium or therapeutically equivalent amounts of water soluble salts of diclofenac according to claim 11, comprising the steps of:

a) suspending said diclofenac sodium or said water soluble diclofenac in the solvent system comprising hydroxypropyl-beta-cyclodextrin and polysorbate 80 in water for injection, with stirring under constant nitrogen 20 purging,
b) optionally, adding potassium dihydrogen phosphate and/or monothioglycerol,
c) adjusting pH between 8-9 using an alkali,
d) further diluting with water for injection to achieve concentration of 25 75mg in 1 ml,
e) sterilizing by sterile filtration and filling in 1 ml ampoules flushed with inert gas prior to sealing. Page 22 of 23

14. A process for the preparation of 1 ml injectable preparation consisting of 75mg of diclofenac sodium or therapeutically equivalent amounts of water soluble salts of diclofenac according to claim 11, comprising the steps of:

a) suspending said diclofenac sodium or said water soluble salt of diclofenac in the solvent system comprising hydroxypropyl-beta-5 cyclodextrin and polysorbate 80 in water for injection, with stirring under constant nitrogen purging,
b) adding potassium dihydrogen phosphate,
c) adjusting pH between 8-9 using an alkali,
d) further diluting with water for injection to achieve concentration of 10 75mg in 1 ml,
e) sterilizing by sterile filtration and filling in 1 ml ampoules flushed with inert gas prior to sealing.
15. A method for treatment or prevention of acute or chronic pain and 15 inflammatory conditions selected from rheumatoid arthritis, osteoarthritis, dysmenorrhea (menstrual pain), headache and migraine, postoperative pain and also for mild to moderate pain after tissue injury, ankylosing spondylitis, pain control of total hip replacement arthroplasty, actinic keratosis and fever, accidental trauma, comprising administering to a 20 subject in need thereof a composition comprising 75 mg/ml of diclofenac sodium or therapeutically equivalent amounts of water soluble salts of diclofenac in a solvent system comprising two or more solublizers in an amount ranging from 0.01 to 40% w/v and water and optionally one or more antioxidant (s) in an amount ranging from 0.10 to 0.5% w/v and/or 25 buffering agent (s) in an amount ranging from 0.05 to 1.0 % w/v, wherein the pH of the composition is maintained at 8-9.