DESC:The following specification particularly describes the invention and the manner in which it is to be performed.

PHARMACEUTICAL FORMULATIONS COMPRISING DICLOFENAC AND PROCESS FOR PREPARING THE SAME

FIELD OF THE INVENTION
The invention relates to pharmaceutical formulations suitable for orally administering diclofenac, more specifically, it concerns pharmaceutical powder formulations comprising diclofenac and process for preparing such formulations.

BACKGROUND OF THE INVENTION
Diclofenac is a non-steroidal anti-inflammatory drug ("NSAID") known chemically as [(2, 6-dichloro-anilino)-2-phenyl]-2-acetic acid. The drug was developed in the 1960s by scientists at Ciba-Geigy and is sold around the world by Novartis under various trade names, including Cataflam® and Voltaren® in the United States.

Owing to its excellent analgesic properties, diclofenac is widely used for treating various types of pain, including both chronic and acute painful episodes. The drug is administered for the treatment of musculoskeletal and joint disorders such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis; periarticular disorders such as bursitis and tendonitis; soft tissue disorders such as sprains and strains, and other painful conditions such as renal colic, acute gout, dysmenorrhoea, and following some surgical procedures. (Martindale (2000) Diclofenac. In: Reynolds, the Extra Pharmacopoeia. London: The Pharmaceutical Press; p. 31-33.) Diclofenac has also been studied for the treatment of headache pain from migraine attacks, using various doses and dosage forms, including 75 mg intramuscular injections (Del Bene et al., Intramuscular treatment of migraine attacks using diclofenac sodium: a cross-over trial. J. Int. Med. Res. 1987; 1544-8), 100 mg suppositories (Del Bene et al., Migraine attack treatment with diclofenac sodium. Cephalalgia 1985; 5:144-5), and 50 mg enteric coated tablets. (Massiou et al., Effectiveness of oral diclofenac in the acute treatment of common migraine attacks: a double blind study versus placebo. Cephalalgia 1991; 1:59-63.)

Migraine attacks manifest a diverse array of symptoms that must be resolved in order for a treatment to be deemed truly effective against migraine (instead of just treating the symptoms). In particular, the treatment must be effective against the pain, photophobia, phonophobia and nausea that are caused by migraine, and it must be effective within the first two hours of treatment, in order to be considered an effective treatment for migraine.

Diclofenac is generally taken orally in the form of immediate release tablets or tablets covered with coatings resistant to gastric juices, capsules. It is also administered topically, or rectally, or by injection. However some of these formulations do not provide rapid onset of action as desired hence a wet granulated formulation of diclofenac potassium was developed to provide an increased rate of absorption. The pharmacokinetic properties of this formulation were tested against commercially available diclofenac potassium tablets. (Reiner et al., Increased absorption rate of diclofenac from fast acting formulations containing its potassium salt. Arzniem.-Forsch./Drug Res. 2001; 51:885-890.) According to the authors, the granular formulation exhibited a higher Cmax, a shorter tmax (i.e. time to Cmax) and a similar AUC when compared to the previous tablet form mentioned above.

Diclofenac powder for oral solution is available as CAMBIA® in US market sold by Nautilus Neurosciences/Kowa. It is indicated for the acute treatment of migraine attacks with or without aura in adults 18 years of age or older.

US Granted Patent No. 7,759,394 (Reiner et.al) describes liquid formulations comprising diclofenac in combination with an alkali metal carbonate or bicarbonate. The formulation is provided as a powder formulation which is dissolved or suspended in water immediately before administration, or as a liquid formulation that is ingested with or without further dilution.

The process for preparing powder formulations of diclofenac described by Reiner et al. produces a powder formulation of diclofenac but suffers from a number of disadvantages including:
1. The process requires precise control measures to be taken at the geometric mixing step to ensure uniform distribution of drug in the mixture and consistent amounts of drug in the finished product leading to higher weight variation.
2. Also by following the process disclosed in Reiner et al. fails to provide formulations with desired pharmaceutical properties and processing parameters.

There is thus need in the art for an alternative process for producing diclofenac powders and other fast acting formulations of diclofenac.

The inventors of present invention have surprisingly discovered an alternative process for preparing pharmaceutical powder formulations of diclofenac by employing unique processing steps.

SUMMARY OF INVENTION
In an embodiment, the invention provides pharmaceutical powder formulation comprising diclofenac and pharmaceutically acceptable salts or esters thereof.

In an embodiment, the invention provides pharmaceutical powder formulation comprising diclofenac, sweetening agent, buffering agent and optionally one or more pharmaceutically acceptable excipients.

In another embodiment, the invention provides pharmaceutical powder formulation comprising diclofenac, sweetening agent, buffering agent, flavoring agent, diluent and lubricant.

In a specific embodiment, the invention provides pharmaceutical powder formulation comprising diclofenac, saccharin, aspartame, potassium bicarbonate, mint flavor, mannitol and glyceryl behenate.
In another specific embodiment, the invention provides pharmaceutical powder formulation comprising
(a) 1-15% of diclofenac;
(b) 0.1%-12% of saccharin and/or aspartame;
(c) 1%-10%of potassium bicarbonate;
(d) 1%-10% of mint flavor;
(e) 1%-95%of mannitol and;
(f) 0.01%-2%of glyceryl behenate.

In another specific embodiment, the invention provides pharmaceutical powder formulation comprising:
(a) about 25-150 mg of diclofenac;
(b) about 1-10 mg of saccharin;
(c) about 10-100 mg of aspartame;
(d) about 10-50 mg of potassium bicarbonate;
(e) about 10-60 mg of mint flavor;
(f) about 100-800 mg of mannitol and;
(g) about 1-5 mg of glyceryl behenate.

In further embodiment, the invention provides process for preparation of pharmaceutical powder formulation of diclofenac comprising:
(a) Sifting diclofenac, diluent, sweetening agent and other pharmaceutically acceptable excipients;
(b) Mixing said materials to obtain uniform blend;
(c) Lubricating said blend using pharmaceutically acceptable lubricant to form pharmaceutical powder formulation and;
(d) Optionally filling the powder in suitable package.

In further embodiment, the invention provides process for preparation of pharmaceutical powder formulation of diclofenac comprising:
(a) Sifting diclofenac, diluent, sweetening agent buffering agent, flavoring agent;
(b) Mixing said materials to obtain uniform blend;
(c) Lubricating said blend using pharmaceutically acceptable lubricant to form pharmaceutical powder formulation and;
(d) Optionally filling the powder in suitable package.

In a specific embodiment, the invention provides process for preparation of pharmaceutical powder formulation of diclofenac comprising:
(a) Sifting diclofenac, mannitol, saccharin, aspartame, potassium bicarbonate and mint;
(b) Mixing said materials to obtain uniform blend;
(c) Lubricating said blend using glyceryl behenate to form pharmaceutical powder formulation and;
(d) Optionally filling lubricated formulation in suitable package.

In another specific embodiment, the invention provides process for preparation of pharmaceutical powder formulation of diclofenac comprising:
(a) Sifting about 25-150 mg of diclofenac, about 100-800 mg of mannitol, about 1-10 mg of saccharin, about 10-100 mg of aspartame, about 10-50 mg of potassium bicarbonate and about 10-60 mg of mint;
(b) Mixing said materials to obtain uniform blend;
(c) Lubricating said blend using about 1-5 mg of glyceryl behenate to form pharmaceutical powder formulation and;
(d) Optionally filling lubricated formulation in suitable package.

In one aspect of this embodiment, the invention provides a method of administering a pharmaceutical powder formulation of diclofenac comprising (a) dissolving powder formulation of diclofenac in water as to form a solution at a concentration of from about 1 to about 100 mg /ml and (b) administering such solution to a patient in need thereof.

Additional advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The advantages of the invention will be realized and attained by means of the elements and combinations. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention.

DETAILED DESCRIPTION OF THE INVENTION
The present invention may be understood more readily by reference to the following detailed description of preferred embodiments of the invention and the Examples included therein.

The terms used herein are defined as follows. If a definition set forth in the present application and a definition set forth in an later filed complete application to which the later application claims priority are in conflict, the definition in the later application shall control the meaning of the terms.

The term “Diclofenac” as used herein means the acid form or free base form or esters or metabolites or polymorphs or solvates or hydrates or alkali and alkaline earth metal salts of diclofenac.

The term “Sweetening Agent” also referred to as or sweetener as used herein means the agent which is used to impart sweet taste perception in subject or mammal.

The term “Buffering Agent” as used herein means the agent which is a weak acid or base used to maintain the acidity (pH) near a desired value after the addition of another acid or base. That is, the function of a buffering agent is to prevent a rapid change in pH when acids or bases are added.

The term “Flavoring Agent” as used herein means the agent which modifies a mixed sensation of taste, smell, all of which involve a combination of physio-chemical and physiological actions that influence the perception of substances.

The term “Package” as used herein covers any suitable and pharmaceutically acceptable container system for storing and dispensing powder formulations as described in the invention, it may be plastic pouch or paper pouch or laminate pouch or suitable sachet, or suitable plastic bottle, glass bottle, metal bottle and the like.

The prior art US granted patent 7,759, 394 (Reiner et.al) teaches powder formulations of diclofenac, the reference also discloses process for preparation of powder formulations wherein diclofenac potassium and mannitol (Fine Quality) are screened and mixed (Premix 1) which is followed by mixing with blend of mannitol (Coarse Quality), Potassium hydrogen carbonate, Aspartame and Saccharin Sodium (Premix 2).
Mannitol (Coarse Quality) and Glyceryl Dibehenate is mixed (Premix 3).
Mannitol (Coarse Quality), Mint Flavor, Anise Flavor is screened and added and mixed with Premix 3 which is then mixed with Premix 2.
This type of mixing is generally termed as geometric mixing which is taught by Reiner et.al.
However this type of process suffers from following processing disadvantages:
1. Lower Powder Flow/ Content Uniformity.
2. Poor particle size distribution.

Inventors of present invention have come up with an alternative process of preparation of pharmaceutical powder formulations of diclofenac which offers good powder flow and blend uniformity by changing the grade of Aspartame (Powder grade Aspartame to Granular Aspartame -100) and by selecting the proper grade of Mannitol (Pearlitol SD 200). Thus present invention provides an alternate and less time consuming process. As noted previously, the invention also concerns methods of making a particulate flowable diclofenac formulation that can be defined by a number of characteristics, including the presence of a coarse powdered diluent, The prior art reference discloses the combination of fine and coarse diluent mannitol, whereas the present invention utilizes only coarse grade of mannitol. The prior art reference discloses the combination of anise and mint flavor, whereas the present invention utilizes only one flavor (mint).
These various features and aspects of the present invention are set forth in greater detail below.

In an embodiment, the invention provides pharmaceutical powder formulation comprising diclofenac and pharmaceutically acceptable salts or esters thereof.

The powder formulation as mentioned include powders or agglomerates.
The diclofenac used in the present invention can be defined by various parameters. In an embodiment not less than 90% of the diclofenac particles have particle size between 1 um to 500 um. The diclofenac can be present in acid or salt form although, owing to its poor solubility in water, diclofenac is normally used in salt form. The salts of diclofenac customarily used are those of sodium, potassium or other alkali and alkaline earth metals, together with salts of organic nature, such as the salts of basic amino acids, such as lysine, arginine and ornithine, or other pharmacologically acceptable organic bases which have the ability to render the resulting salt soluble in water. Diclofenac potassium is preferably used in this invention due to its fast onset of action. In a preferred embodiment, 50 mg of diclofenac or its salt is used in the final dosage form, although other amounts could be used including 12.5, 25, 37.5, 50, 75, 100 or 150 mg of diclofenac, or a range having as endpoints any of the foregoing amounts. The amount of diclofenac preferably does not vary by more than about 90-105% from dose to dose.

In an embodiment, the invention provides pharmaceutical powder formulation comprising diclofenac, sweetening agent, buffering agent and optionally one or more pharmaceutically acceptable excipients.

In another embodiment, the invention provides pharmaceutical powder formulation comprising diclofenac, sweetening agent, buffering agent, flavoring agent, diluent and lubricant.

Pharmaceutically acceptable excipients includes but are not limited to sweetening agents, buffering agents, flavoring agents, diluents, lubricants, opacifiers, colorants, preservatives, surfactants, binders, glidants, disintegrants, plasticizers, solvents and other suitable excipients and combinations thereof.

The sweetening agents includes but are not limited to sugar, invert sugar, sorbitol, maltitol, aspartame, saccharin, sucrose, honey, dextrose, glucose or glucose solids or combinations thereof in dry or liquid form. The sweetening agents are used in the concentration of about 0.1- 12%. The sweetening agents which are used in the invention (for illustrative purpose only) are aspartame (NutraSweet Granular™) and saccharin.

The buffering agents includes but are not limited to alkali metal carbonates and bicarbonates and these agents are preferably employed in a weight ratio relative to the diclofenac of greater than about 1:1, 1:2, 1:2.5, 1:4 or 1:6. Particularly preferred alkali metal bicarbonates are sodium bicarbonate and potassium bicarbonate. In a preferred embodiment for powder, the buffering agent controls the pH of the formulation when dissolved in water, and preferably yields a pH greater than about in the range of 6.3-7.5.

The flavoring agents includes but are not limited to cherry, maple, pineapple, orange, raspberry, banana-vanilla, butterscotch, coconut-custard, fruit-cinnamon, strawberry, vanilla, Apricot, cherry, cinnamon, grape, honey, lime, peach-orange, peachrum, raspberry, wild cherry. Banana-pineapple, banana-vanilla, cinnamon-mint, orange, peach-orange, grenadine-strawberry, Anise, apricot, butterscotch, cherry, coconut-custard, custard-mint strawberry, grenadine-peach, strawberry-lemon, gooseberry, orange lemon, coriander, pineapple, raspberry, Cherry, grape, lemon-lime, raspberry, wild cherry syrup, grenadine strawberry, lime, port wine, cherry wine, wild-strawberry and combinations thereof. The flavoring agent used in the invention (for illustrative purpose only) is mint flavor. The mint flavor is generally obtained from menthol which is extracted from plant or other sources. Flavoring agents can be used in the concentration range of 1-10%.

The diluents also referred to as filler, dilutant as used herein means an agent which can be used impart bulk to the formulation Suitable diluents includes but are not limited to, microcrystalline cellulose (“MCC”), silicified MCC (e.g., PROSOLV™), microfine cellulose, lactose, starch, pregelatinized starch, mannitol, sorbitol, dextrates, dextrin, maltodextrin, dextrose, calcium carbonate, calcium sulfate, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, magnesium carbonate, magnesium oxide and combinations thereof.
The diluents are used in the concentration of about 1- 95%. The diluent used in the invention (for illustrative purpose only) is mannitol; various grades of mannitol were tried in the experimental part. Mannitol is commercially available in grades like Pearlitol® 25C, Pearlitol® 200 SD, Pearlitol® 300 DC and Pearlitol® 400 DC.

TABLE 1
Type Mean diameter (µm) Type
Pearlitol® 25C 25 Extra-fine
Pearlitol® 200 SD 180 Spray-dried
Pearlitol® 300 DC 250
Granulated
Pearlitol® 400 DC 360

The lubricant as used herein means an agent which prevents ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Lubricants also ensure that tablet formation and ejection can occur with low friction between the solid and die wall. Lubricants may also improve flow of lubricated blend or mixtures. Suitable lubricants includes but are not limited to, stearic acid, talc, hydrogenated cottonseed oil and magnesium stearate, colloidal silicon dioxide; and such surfactants as polysorbate and sodium lauryl sulfate, glyceryl dibehenate and combinations thereof. Lubricants are used in the concentration of 0.01-2 %. The lubricant used in the invention (for illustrative purpose only) is glyceryl dibehenate.

As set forth above, the pharmaceutical formulations for oral administration may also include binders or adherents such as acacia, guar gum, alginic acid, dextrin, maltodextrin, methylcellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose (e.g., KLUCEL®), low substituted hydroxypropyl cellulose, hydroxypropyl methylcellulose (e.g., METHOCEL®), carboxymethyl cellulose sodium, povidone (various grades of KOLLIDON®, PLASDONE®), starch and the like; disintegrants such as carboxymethyl cellulose calcium, croscarmellose sodium, (e.g., Ac-Di-Sol®, PRIMELLOSE®), crospovidone (e.g., KOLLIDON®, POLYPLASDONE®), povidone K-30, polacrilin potassium, starch, pregelatinized starch, sodium starch glycolate (e.g., PRIMOGEL, EXPLOTAB®), and the like; plasticizers such as acetyltributyl citrate, phosphate esters, phthalate esters, amides, mineral oils, fatty acids and esters, glycerin, triacetin or sugars, fatty alcohols, polyethylene glycol, ethers of polyethylene glycol, fatty alcohols such as cetostearyl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, myristyl alcohol and combinations thereof.

Pharmaceutical powder formulation described herein may further include any one or more of pharmaceutically acceptable opacifiers, colorants, preservatives and other commonly used carriers.

The pharmaceutical powder formulation described herein may further comprise surfactants. Examples of such surfactants include, but are not limited to, poloxamer, polyoxyethylene sorbitan esters (known as POLYSORBATE or TWEEN), polyethoxylated castor oil (CREMOPHOR), methyl glucose sesquistearate, PEG-20 methyl glucoside sesquistearate, Steareth-21, polyethylene glycol 20 sorbitan monostearate, polyethylene glycol 60 sorbitan monostearate, polyethylene glycol 80 sorbitan monostearate, Steareth-20, Ceteth-20, PEG-100 stearate, sodium stearoyl sarcosinate, hydrogenated lecithin, sodium cocoylglyceryl sulfate, sodium stearyl sulfate, sodium stearoyl lactylate, PEG-20 glyceryl monostearate, sucrose monostearate, sucrose polystearates, polyglyceryl 10 stearate, polyglcyeryl 10 myristate, steareth 10, DEA oleth 3 phosphate, DEA oleth 10 phosphate, PPG-5 Ceteth 10 phosphate sodium salt, PPG-5 Ceteth 10 phosphate potassium salt, steareth-2, PEG-5 soya sterol oil, PEG-10 soya sterol oil, diethanolamine cetyl phosphate, sorbitan monostearate, diethylene glycol monostearate, glyceryl monostearate, and combinations thereof.

The pharmaceutical powder formulation described herein may further contain one or more suitable solvents. Examples of such solvents include, but are not limited to, water; tetrahydrofuran; propylene glycol; liquid petrolatum; ether; petroleum ether; alcohols, e.g., methanol, ethanol, isopropyl alcohol and higher alcohols; aromatics, e.g., benzene and toluene; alkanes, e.g., pentane, hexane and heptane; ketones, e.g., acetone and methyl ethyl ketone; chlorinated hydrocarbons, e.g., chloroform, carbon tetrachloride, methylene chloride and ethylene dichloride; acetates, e.g., ethyl acetate; lipids, e.g., isopropyl myristate, diisopropyl adipate and mineral oil and combinations thereof.

In a specific embodiment, the invention provides pharmaceutical powder formulation comprising diclofenac, saccharin, aspartame, potassium bicarbonate, mint flavor, mannitol and glyceryl behenate.

In another specific embodiment, the invention provides pharmaceutical powder formulation comprising
(g) 1-15% of diclofenac;
(h) 0.1%-12% of saccharin and/or aspartame;
(i) 1%-10%of potassium bicarbonate;
(j) 1%-10% of mint flavor;
(k) 1%-95%of mannitol and;
(l) 0.01%-2%of glyceryl behenate.

In another specific embodiment, the invention provides pharmaceutical powder formulation comprising:
(a) about 25-150 mg of diclofenac;
(b) about 1-10 mg of saccharin;
(c) about 10-100 mg of aspartame;
(d) about 10-50 mg of potassium bicarbonate;
(e) about 10-60 mg of mint flavor;
(f) about 100-800 mg of mannitol and;
(g) about 1-5 mg of glyceryl behenate.

The inventors have surprisingly discovered an alternative process for preparing pharmaceutical powder formulation of diclofenac.

In an embodiment, the invention provides an alternative process for preparing pharmaceutical powder formulation comprising diclofenac that is based predominantly on the large proportion of mannitol in the formulation, which preferably includes a precise control of particle size of diluents in the finished product. The large proportion of mannitol imparts rapid bioavailability to the formulation, while the control of particle size assures uniform distribution of diclofenac in the material used to fill the sachets and consistent amounts of drug in each sachet without the use of sugar or large amounts of diluent as taught in the prior art.

In further embodiment, the invention provides process for preparation of pharmaceutical powder formulation of diclofenac comprising:
(a) Sifting diclofenac, diluent, sweetening agent and other pharmaceutically acceptable excipients;
(b) Mixing said materials to obtain uniform blend;
(c) Lubricating said blend using pharmaceutically acceptable lubricant to form pharmaceutical powder formulation and;
(d) Optionally filling the powder in suitable package.

In further embodiment, the invention provides process for preparation of pharmaceutical powder formulation of diclofenac comprising:
(a) Sifting diclofenac, diluent, sweetening agent buffering agent, flavoring agent;
(b) Mixing said materials to obtain uniform blend;
(c) Lubricating said blend using pharmaceutically acceptable lubricant to form pharmaceutical powder formulation and;
(d) Optionally filling the powder in suitable package.

Sifting step described in the above embodiment can achieved using sieves of different mesh size (usually 40 # for other ingredients and 60 # for mint flavor) using suitable sieving machine such as vibrating screeners so as to obtain uniform particle size of diclofenac and excipients. Subsequent mixing is done using suitable blending machine such as double cone blender and mixing is performed for 10-30 minutes preferably 15 minutes at 20-30 RPM preferably 20 RPM.
In other step of processing, the mixture is lubricated using suitable lubricant preferably glyceryl dibehenate used in the concentration of 0.02 %. Lubricated blend can be filled into suitable package.

In a specific embodiment, the invention provides process for preparation of pharmaceutical powder formulation of diclofenac comprising:
(a) Sifting diclofenac, mannitol, saccharin, aspartame, potassium bicarbonate and mint;
(b) Mixing said materials to obtain uniform blend;
(c) Lubricating said blend using glyceryl behenate to form pharmaceutical powder formulation and;
(d) Optionally filling lubricated formulation in suitable package.

In another specific embodiment, the invention provides process for preparation of pharmaceutical powder formulation of diclofenac comprising:
(a) Sifting about 25-150 mg of diclofenac, about 100-800 mg of mannitol, about 1-10 mg of saccharin, about 10-100 mg of aspartame, about 10-50 mg of potassium bicarbonate and about 10-60 mg of mint;
(b) Mixing said materials to obtain uniform blend;
(c) Lubricating said blend using about 1-5 mg of glyceryl behenate to form pharmaceutical powder formulation and;
(d) Optionally filling lubricated formulation in suitable package.

While the preferred method of manufacturing the formulation of the present invention is dry blending; other methods can also be employed that do not depend on mixing of dry powders including wet granulation. For wet granulation, the binder can be added dry to the powder blend, or as a solution in the solvent. The solvent is usually ethanol, water, or a mixture of both. The actual granulation is performed in either a high-shear, or low-shear type mixer. Low-shear granulation requires cheaper equipment and produces a more porous granule. High-shear granulation is faster and affords good control over particle size.

Fluid bed wet granulation is a variation of the process in which the granulation and drying is carried out in the same vessel (a fluid bed granulator). The powder mix is fluidized by dry air inside a chamber. The binder solution is sprayed onto the fluidized powder to form the agglomerates. Air fluidizing continues until the agglomerates are dry. The process requires expensive equipment, but is simpler and produces a very porous low-density granule, which can result in faster drug dissolution. Slow drug dissolution is sometimes a problem associated with wet granulation, as the active ingredient is locked into the granule, and initial tablet disintegration liberates the granules rather than the primary drug particles.

In dry granulation, particle size enlargement is achieved by aggregating the powder particles under high pressure (i.e., by compaction) then milling the compressed material to the desired size. Fines generated by milling are recycled back through the compactor. The compression step is typically carried out in a roller compactor in which the powder is compressed between two rollers.

In one aspect of this embodiment, the invention provides a method of administering a pharmaceutical powder formulation of diclofenac comprising (a) dissolving powder formulation of diclofenac in water as to form a solution at a concentration of from about 1 to about 100 mg /ml and (b) administering such solution to a patient in need thereof.

It will be understood that various modifications may be made to the embodiments disclosed herein. Therefore the above description should not be construed as limiting, but merely as exemplifications of preferred embodiments. Other arrangements and methods may be implemented by those skilled in the art without departing from the scope and spirit of this invention.
The following examples are provided to enable one skilled in the art to practice the invention and are merely illustrative of the invention. The examples should not be read as limiting the scope of the invention.

EXAMPLES
Quantitative Composition:
Batch size: 3300 sachets
Blender and capacity: Double cone blender 8 liter
Occupancy: 70%
TABLE 2
Sr. No: Name of the Component Unit(mg)/ Sachet
Example 1 Example 2 Example 3
01 Diclofenac potassium 50 50 50
02 Mannitol (Pearlitol 25C) 72.1 0 0
03 Mannitol ( Pearlitol 200 SD) 648.9 721 721
04 Mannitol ( Pearlitol 300 DC) 0 0 0
05 Mannitol ( Pearlitol 400 DC) 0 0 0
06 Saccharin sodium 5 5 5
07 Potassium Bicarbonate 22 22 22
08 Mint flavor 35 50 50
09 Anise flavor 15 0 0
10 Aspartame 50 50 0
11 Aspartame granular 60 0 0 0
12 Aspartame granular 100 0 0 50
13 Glycerol Dibehenate 2 2 2
Total weight 900.0 900.0 900.0

Brief Manufacturing Process:

Sifting and Blending:
Dry mixing:
Sift diclofenac potassium, mannitol, potassium bicarbonate, aspartame & saccharin sodium (#40 pass) through #40 mesh followed by flavors through #60 meshes and resift through #40 mesh. Load sifted materials in double cone blender and mix for 15 minutes at 20 rpm.

Lubrication:
To the above blend add Glyceryl Behenate (sifted through #60 mesh) and continue mixing for 2 minutes at 20 rpm.

Sachets Filling: By using sachet filling machine.

TABLE 3
Sr. No Evaluation parameters Example 1 Example 2 Example 3
1. Description White Powder White powder White Powder
2. Bulk density (g/mL) 0.562 0.470 0.530
3. Tap density (g/mL) 0.666 0.635 0.646
4. Compressibility Index 15.62 26 18
5. Hausner ratio 1.185 1.35 1.22
6. Angle of repose -- 35.5 30.2
7. Flowdex -- 63 250
8. pH of solution (1 sachet in 60 mL DW) 7.4 -- --
9. Assay -- 99.2 99.9
10.
LOD (% w/w)
0.89
0.9
0.9

11. Particle size distribution % Weight retain
# 20 0

NA 0
# 40 0.67 0
# 60 2.51 2.6
# 80 7.92 10.2
# 100 21.63 19.6
# 120 26.84 25.4
# 200 28.42 31.8
Pan 11.63 10
12. Content Uniformity
1

NA 99.2 102.3
2 102.2 101.8
3 100.6 104
4 100 102.3
5 100.8 102.1
6 99.9 103.4
Avg 100.5 102.7
RSD 1 0.8
Min 99.2 101.8
Max 102.2 104

As seen from Evaluation Data in Table 3 the formulation of Example 3 shows good the Content Uniformity as well as more uniform particle size distribution. So it is evident from the Table 3
Evaluation parameters that the formulation prepared by following the processing steps of the instant invention achieved the desired pharmaceutical properties and parameters when compared to prior art formulations hence can be commercially effective.

Throughout this application, various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains. It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein.
,CLAIMS:1. A pharmaceutical powder formulation comprising diclofenac and one or more pharmaceutically acceptable excipients.

2. The pharmaceutical powder formulation according to claim 1, wherein diclofenac is diclofenac potassium.

3. The pharmaceutical powder formulation according to claim 1, wherein one or more pharmaceutically acceptable excipients are selected from the group consisting of sweetening agent, buffering agent, flavoring agent, diluent and lubricant.

4. The pharmaceutical powder formulation according to claim 3, wherein the buffering agent is selected from the group consisting of alkali metal carbonates and bicarbonates.

5. A pharmaceutical powder formulation comprising
(a) 1-15% of diclofenac;
(b) 0.1%-12% of saccharin and/or aspartame;
(c) 1%-10%of potassium bicarbonate;
(d) 1%-10% of mint flavor;
(e) 1%-95%of mannitol and;
(f) 0.01%-2%of glyceryl behenate.

6. A pharmaceutical powder formulation comprising
(a) about 25-150 mg of diclofenac;
(b) about 1-10 mg of saccharin;
(c) about 10-100 mg of aspartame;
(d) about 10-50 mg of potassium bicarbonate;
(e) about 10-60 mg of mint flavor;
(f) about 100-800 mg of mannitol and;
(g) about 1-5 mg of glyceryl behenate.

7. A pharmaceutical powder formulation comprising diclofenac and one or more pharmaceutically acceptable excipient(s), wherein the pharmaceutical powder formulation is prepared by the steps of:
a). Mixing diclofenac and one or more pharmaceutically acceptable excipients;
b). Adding one or more pharmaceutically acceptable excipients; optionally filling the powder in suitable package.

8. A pharmaceutical powder formulation and process for the preparation substantially as described and illustrated in the examples herein.