FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
1. Title of the invention : "Ready to use compositions for β-blockers "
2. Applicant(s)

(a) NAME : IDEAL CURES PVT. LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS : A-223-229,2nd floor, Virwani Industrial Estate, Off. Western Express Highway, Goregaon (East), Mumbai - 400 063. E-mail- patent@idealcures.co.in
3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed.

Ready to use compositions for Non-steroidal anti-inflammatory drugs (NSAIDs) Technical Field
The present invention relates to a dry ready to use modified release dosage formulation composition comprising a blended matrix of cellulosic polymers components having plurality of layers thereby providing controlled release rate of Non-steroidal antiinflammatory drugs {NSAIDs) from the formulation/tablet. Dry composition are applicable to drug, veterinary and agricultural formulation, it could be applied to the retarded release of fertilizers, insecticides or specific protection agents. Invention also relates to ready-to-use modified release compositions capable of regulating release of Non-steroidal antiinflammatory drugs (NSAIDs)at various dosage strength, a process for production thereof and also use thereof as formulated pharmaceutical compositions.
Background or Information on Art
Non-steroidal anti-inflammatory drugs (NSAIDs) provides anti-inflammatory (inflammation or associated pain reducing), analgesic (pain reducing), and antipyretic (fever-reducingjactivity in humans. Almost all NSAIDs have more of less similar action mechanism of non-selective inactivation of organism enzyme cyclooxygenase or its isoenzymes like COX-1 and COX-2. This enzyme catalyzes the synthesis of prostaglandins and thromboxane from arachidonic acid. Prostaglandins have function of messenger molecules which helps in process of inflammation recognition. NSAID class of drug is represented by many pharmaceutical drugs namely ibuprofen, aceclofenac, diclofenac or diclofenac-Na etc.
In practice drugs are formulated as low concentration dosage to avoid related toxicity and other adverse side-effects or medical complications, but sometimes it is essential to maintain certain level of medications in blood stream. This can either achieved by repeated dose after every 3-4 hours or administration of a modified release formulated medication. Later is also termed as sustained release or extended release dosage and it offers numerous

advantages to patients besides maintaining drug quantity in body for long duration through one dose.
Diclofenac is one of the prominent representative of NSAID family apparently half-life of these drug are very short so in order to maintain therapeutic levels in the blood plasma, therefore it is necessary that the drug be provided repeatedly after specific intervals. Sustained release composition are suitable for such drugs as they help by increasing patient compliance and maintain sufficient levels of the drug over long period of time.
Certain prior art discloses controlled release compositions for anti-inflammatory drugs. US4968505 discloses a long acting composition comprising diclofenac sodium wherein the sustained release activity of the drug is obtained by coating the dosage form with a sustained release coating comprises components selected from polyvinylpyrrolidone, ethylcellulose, acrylic acid copolymer and other auxiliary ingredients. Similarly US4948581 also discloses such compositions where the active drug is diclofenac sodium and is coated with an enteric coating that provides the controlled release profile for the drug.
US2002051817 discloses a once a day sustained release composition comprising diclofenac sodium or its pharmaceutical^ acceptable salt. Composition comprises hydroxyl-ethyl cellulose, Lactose, Polyvinylpyrrolidone and other auxiliary ingredients. The compositions are aimed at release of not more than 10% of active ingredient at a pH of less than 4.5 and more than 50% at a pH of more than 6.5.
US patent application US2004115267 provide delayed release composition comprising a combined dosage form of Diclofenac and Tramadol. Composition comprises microcrystatline cellulose, substituted hydroxypropylcellulose, Dibutyl sebacate, lactose and other auxiliary ingredients. Additionally these compositions use sustained release formulation for obtaining delayed release properties.
In yet another US patent application US2012183611 discloses preparations of diclofenac potassium comprising an immediate release and a sustained release portion that are

compressed to form a single dosage form. Composition comprises sodium starch giycolate, microcrystalline cellulose, HPMC and other auxiliary ingredients.
Furthermore, it is seen that NSAIDs can cause stomach irritation and sometimes peptic ulceration and gastrointestinal bleeding, it would thus be desirable to have a drug delivery system that is capable of providing the controlled delivery of NSAIDs or their pharmaceutically acceptable salts in a predictable manner over a long period of time.
Although many methods and formulation has been derived in prior art but it has become desirable to provide ready-to-use formulation composition for modified release profiles, an objective not contemplated in other prior art as most of them requiring lengthy step by step procedures to prepare final formulation or coating methods. It is understood that by adjusting the amount and composition of the excipients, the control release characteristic of the final composition can be altered. However, formulating a correct blend of ingredients that provide similar control release character from time to time is a very time consuming and tedious task. Superior advantages of modified release formulation are well known in industry and it also significantly improves patient acceptability by reducing dosage regimen.
It is therefore an object of the present invention to provide a ready-to-use, stable modified release composition which can be used for a wide variety of therapeutically active drugs.
It is an object of the present invention to provide a ready-to-use, stable modified release composition for Non-steroidal anti-inflammatory drugs (NSAIDs).
It is another object of the present invention to provide a ready-to-use, stable modified release composition having the properties set forth above which can be used with both relatively soluble and relatively insoluble therapeutically active drugs
It is a further object of the present invention to provide a ready-to-use, stable modified release composition which is relatively inexpensive to manufacture.

Summary of Invention
In accordance with the above-mentioned objectives, the present invention provides a ready-to-use, stable modified release composition comprising a blended matrix of cellulosic polymers components having plurality of layers thereby providing controlled release rate of Non-steroidal anti-inflammatory drugs (NSAIDs) or their pharmaceutical^ acceptable salts from the formulation/tablet.
In accordance with the above-mentioned objectives, the present invention provides a ready-to-use, stable modified release composition comprising a blended matrix of cellulosic polymers components having plurality of layers for Diclofenac or diclofenac-Na.
In another aspect, present inventive composition optionally further comprises other pharmaceutically acceptable excipients, bulking agents, flavoring agents, coloring agents, additional lubricants and like.
In further aspect, present invention provides a ready-to-use, stable modified release composition which is relatively inexpensive to manufacture for Non-steroidal antiinflammatory drugs (NSAIDs).
The details of one or more embodiments in the practice of the inventions are set forth in the description below. Other features, objects and advantages of the inventions will be apparent from the appended examples and claims.
Drawings
if any
Detailed description
Unless specified otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art, to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred

methods and materials are described. To describe the invention, certain terms are defined herein specifically as follows.
Unless stated to the contrary, any of the words "having" "including," "includes," "comprising," and "comprises" mean "including without limitation" and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it. Embodiments of the invention are not mutually exclusive, but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention as set forth the appended claims.
The term "ready-to-use", in the context of the present invention, is taken to mean that, the composition according to the invention may be used directly without further processing for its purposes by the user as simply mixing inventive composition in required quantity of active ingredient.
The term "active ingredient", in the context of the present invention, is taken to mean Non-steroidal anti-inflammatory drugs (NSAIDs) or their pharmaceutically acceptable salts or combination thereof.
The term 'Lubricant' in the context of the present invention, is taken to mean that a ingredient added to prevent the adhesion of tablet materials to the punches and dies, reduce inter-particle friction and facilitate the ejection of oral dosage forms from the die cavity.
The term 'Solvent' in the context of the present invention, is taken to mean ingredient that facilitate mixing of components in wet granulation process. Solvent can be used in present invention includes but not limited to Acetone, ethanol, methylene di chloride, isopropyl alcohol, water or their mixture thereof.
The term 'filler' in the context of the present invention, is taken to mean ingredient that facilitate weight gain. Filler can be used in present invention includes but not limited to

lactose, lactose monohydrate, dibasic calcium phosphate (anhydrous), Micro-crystalline cellulose and like.
Unexpectedly, inventors have found that when Non-steroidal anti-inflammatory drugs (NSAIDs) are formulated with a mixed matrix of cellulosic polymers components having plurality of layers have advantageous sustained release properties.
Cellulosic polymer are polymer of glucose subunits having β(1→4)-glycosidic bonds. Some of the cellulosic polymer were chemically modified to provide additional abilities like stability, charge neutralization includes but not limited to ether derivatives (like Alkyl, hydroxyalkyl, carboxy alkyl etc.) organic and inorganic esters. Cellulosic polymer according to invention includes but not limited to derivative cellulose, ethyl cellulose, methyl cellulose, ethyl methyl cellulose, Hydroxyethyl cellulose, hydroxyproplyl cellulose, hydroxy propyl methyl cellulose, hydroxyethyl methyl cellulose, ethyl hydroxyethyl cellulose, and like.
These derivatives of cellulosic polymers have an average molecular weight of about few hundreds to thousands (e.g. HPMC 25,000-300,000 Da). Cellulosic polymers having higher molecular weights known to have wide range of fluid resistance parameters known as viscosity (100-10,000 mPa).
Upon administration of dosage form in patient present inventive formulation comprising a mix of cellulosic polymers, and active ingredient reaches in gastric juices the cellulosic polymer portion of the formulation absorbs the moisture and creates a gel like substances. In accordance with present invention mixture of lower viscosity grade polymer is mixed with higher viscosity grade polymer.
It is well known in state of art that active component of the drug disperse in body through erosion. It was surprisingly observed that due to increased moisture absorbing affinity of higher viscosity grade cellulosic polymer and lower moisture absorbing affinity of lower viscosity grade cellulosic polymer create physical tension in drug covering layer. In accordance with this observation one can achieve numerous combination of cellulosic polymeric mixture. Upon absorbing moisture polymer forms a gel like substance but due to

absorbing differences of varying viscosity grade prolonged drug release is achieved. Therefore due to this physical barrier active ingredient is release in sustained delivery manner.
The amount of cellulosic polymer employed in ready to use composition according to the invention is from 30 to 50% by weight of the ready to use composition. Advantageously according to one of the embodiment the cellulosic polymer comprising a major proportion of HPMC in range of 32- 48 %, particularly 35-45%, by weight of the ready to use composition.
The amount of cellulosic polymer employed in ready to use composition according to the invention further comprise lower and higher viscosity grade cellulosic polymer, wherein higher viscosity grade polymer is from 20 to 31% more preferably 21 to 30% by weight of the ready to use composition. Further lower viscosity grade polymer is from 10 to 20% more preferably 11 to 19% by weight of the ready to use composition.
The cellulosic polymer according to present invention allows the release of the Non-steroidal anti-inflammatory drugs (NSAIDs) from the formulation over a period of time greater than that expected from a conventional immediate release tablet. In yet another embodiment of the present invention cellulosic polymer is mixed with different viscosity grades of the same or variant cellulosic polymer.
The cellulosic polymer according to one of the main embodiment of present invention is hydroxyl propyl methyl cellulose HPMC allows the release of the Non-steroidal antiinflammatory drugs (NSAIDs) from the formulation over a period of time greater than that expected from a conventional immediate release tablet.
Alternatively in one of the aspect of present invention ready to use composition is obtained addition of one more fillers with cellulosic polymer. Therefore optionally if desired, a proportion of the cellulosic may be replaced by filler.

The filler according to the present invention includes but is not limited to lactose, lactose monohydrate, dibasic calcium phosphate (anhydrous), microcrystalline cellulose, and further may include calcium sulphate, cellulose, kaolin, mannitol, sodium chloride, powdered sugar, dry starch etc. The amount of filler employed in a formulation according to the invention is from 50 to 75% by weight of the ready to use composition. Advantageously according to one of the embodiment filler comprises 59-65%, by weight of the ready to use composition.
The ready to use composition in accordance with present invention comprise cellulosic polymer with filler. In one of the embodiment of present invention cellulosic polymer is selected from pool of cellulosic polymer having variable viscosity strength, molecular weight. In accordance with present invention different cellulosic polymer could be combined to achieve ready-to-use composition.
In a preferred formulation according, to the invention the pharmacologically active ingredient comprises Non-steroidal anti-inflammatory drugs (NSAIDs). Particularly suitable NSAID for a formulation according to the invention are selected from the group consisting of ibuprofen, flurbiprofen, diclofenac, aceciofenac, naproxen, ketoprofen and their pharmaceutically acceptable salts. Preferably the NSAID is diclofenac or diclofenac-Na. and their pharmaceutically acceptable salts. In accordance with one embodiment of invention advantageous sustained release properties are obtained when diclofenac or diclofenac-Na is combined with cellulosic polymer with plurality of viscosity strength through wet granulation. Especially advantageous sustained release properties are obtained when diclofenac or diclofenac-Na is combined with cellulosic polymer comprising a major proportion of HPMC in a formulation according to the invention. In accordance with invention solvent used for wet granulation comprise uniform mixture of two or more solvents. The ratio of solvent is in range of 70:30 to 90:10, preferably 75:25 to 85:15 more preferably 80:20. In one of the embodiment solvent used are isopropyl alcohol and water in range of 75:25 more preferably 80:20.

In a formulation according to the invention the pharmacologically active ingredient is blended with the inventive ready to use composition and the mixture is compressed to produce a solid formulation. Preferably the ingredients are blended to form a uniform powder and then compressed with means generally known to skilled in the art. Optionally a lubricant can be added to facilitate compression of tablets. Appropriately the inventive composition and pharmacologically active ingredient are blended substantially throughout the whole solid formulation. Solid formulation thus prepared could be further coated with other means for shiny look, palatability, taste masking, pigmentation, distinguishing marking, grooves and like.
Lubricants of the present invention comprise silicon dioxide, aerosil, magnesium stearate, stearic acid, talc, calcium stearate, glyceryl behanate, hydrogenated vegetable oils and the like. The amount of lubricant employed in a formulation according to the invention is from 0.1 to 5% by weight of the formulation. Advantageously according to one of the embodiment lubricant comprises 0.2 - 3 %, particularly 0.5-2%, by weight of the formulation.
In particular, when formulations comprise diclofenac-Na the formulations thereby achieved are therapeutically effective and exhibit desired bioavailability characteristics. Furthermore, the controlled release formulation achieved with inventive composition with Diclofenac or diclofenac-Na it is observed that active drug molecules retains upto 24 hours or even more in accordance with some of the embodiment of invention. In standards of pharmacological drug delivery such formulation which delivers drug upto 24 hours or more could be termed as once a day formulation, providing a patient compliance and one dose per day regimen.
Accordingly other pharmaceutically acceptable excipients may be combined to produce modified release formulation. It is anticipated that such excipients may be added to further modify rate of drug availability in body or may support other property which assist successful tablet manufacturing. Pharmaceutically acceptable excipient may be added in sufficient and appropriate quantities for successful dosage composition include, but are not limited to fatty acid and derivatives e.g. stearic acid, metallic stearates, stearyl alcohol,

hydrogenated cotton seed oil, polyethylene glycol and like; lactose, sucrose, alginic acid and like. The pharmaceutically acceptable excipients may be applicable recognized by those skilled in the art are listed in Wade, A. and P. J. Wetler (1994). Handbook of pharmaceutical excipients. Pharmaceutical press incorporated herein for reference only. Quantity of such pharmaceutically acceptable excipient varies according to their role and quality/grades. In one of the embodiment of present invention the quantity of pharmaceutically acceptable excipients used is suitably up to 10%, preferably up to 5% and more preferably up to 2% by weight of the total composition.
According to present invention dosage form of Non-steroidal anti-inflammatory drugs (NSAIDs) is greater than 10 mg, in some of the non-limiting embodiment of present invention NSAIDs is exemplified with diclofenac-Na. In particular NSAIDs are used in ratio of about 30-40 % of final formulated dosage formulation.
Preferred formulations according to the invention are obtained when the compositions comprise Non-steroidal anti-inflammatory drugs (NSAIDs) about 30-40 % and inventive ready to use composition comprising cellulosic polymer about 58-70% by weight of final formulated dosage form. In accordance with one of the embodiment preferred formulations comprise Non-steroidal anti-inflammatory drugs (NSAIDs) about 32-38 % and inventive ready to use composition comprising cellulosic polymer about 59-69% by weight of final formulated dosage form.
Preferred formulations according to the invention are obtained when the compositions comprise diclofenac-Na about 30-40 % and inventive ready to use composition comprising cellulosic polymer about 58-70% by weight of final formulated dosage form. In accordance with one of the embodiment preferred formulations comprise diclofenac or diclofenac-Na about 32-38 % and inventive ready to use composition comprising cellulosic polymer about 59-69% by weight of final formulated dosage form.
It is well known in the art that controlled release formulation solid dosage form can be provided in standard pharmacologically accepted form, in accordance with present

invention some of the solid dosage form prepared include but not limited too, capsules, tablets, various suppositories, pessary, lozenges or implants, skin patches or like etc. According to one of the main embodiment of present invention preferably tablet formulations are prepared and intended to release the drug molecules slowly after predetermined controlled release within alimentary canal of organism including oesophagus, stomach, intestine and respective organ cavities. Optionally produced dosage form may be further coated with suitable coating composition to improve taste-masking, delivery, sweetening, flavor etc.
According to one of the main embodiment of present invention solid dosage formulation is prepared through conventional dosage preparation methods listed in Swarbrick, J. and J. C. Boylan (2001). Encyclopedia of pharmaceutical technology; Association, A. P. (1986) "Handbook of pharmaceutical excipients" incorporated herein by reference only. Preferably one of the embodiments uses combination of method like slugging and tablet compression to generate final dosage formulation. Accordingly inventive ready to use composition is prepared by combining Cellulosic polymer and filler in dry blender with pharmaceutically acceptable excipients.
Inventive formulation may be prepared by blending Non-steroidal anti-inflammatory drugs (NSAIDs), their derivatives or combination thereof along with inventive composition. Therefore inventive formulation preparation comprise steps as
1. Blending of cellulosic polymer(s) and filler
2. Thorough mixing to form dry powder
3. Wet granulation with NSAIDs and solvent
4. Sieving through appropriate size
5. Tray drying or fluidized bed drying
6. Optionally addition of lubricant
7. Final tablet compression
Initially inventive ready to use composition is prepared by blending desired quantity of cellulosic polymer(s) along with filler to form 'ready to use powder'preferred process

blending is performed by conventional dry blender or a food processor or "V-blender" or a similar function device. According to one of the embodiment inventive formulations are prepared by blending Non-steroidal anti-inflammatory drugs (NSAIDs) along with inventive ready to use composition. Further NSAIDs are blended with 'ready to use powder'using solvent through wet granulation or a similar wet mixing method to generate dosage formulation. Dosage formulation is further tray dried, sieved and compressed optionally with addition of lubricant to form oral dosage form.
In one of the embodiment of present invention, inventive dosage formulations are prepared by blending NSAIDs along with inventive ready to use composition. Initially cellulosic polymers having different viscosity strength and filler are blended to form 'ready to use composition' preferred process of mixing is by conventional dry blending in a food processor or "V-blender" or a similar function device. Upon dry blending composition is sieved to get fine particles (e.g. 40 mesh). Further NSAIDs are blended with 'ready to use composition' with dry mixing method followed by mixing with appropriate quantity of solvent and wet granulating of blended dosage formulation. Dosage formulation is further tray dried at 40-45°C to make it dry. Generated dry powder sieved to get fine particles (e.g. 20 mesh). Inventors observed that sieving quality and fineness of blended dosage formulation provide excellent compression and desired controlled release function. Therefore it is recommended that in any formulation to produce consistent controlled release formulation uniform size of the blended blend is essential. Obtained sieved blend is then uniformly mixed with premeasured amount of the lubricant to improve industrial acceptability and oral dosage compression quality. Subsequently uniform mixed inventive formulation is compressed in standard pharmacopoeial equipment to get a controlled release oral dosage formulation of the correct desired weight and strength.
The controlled release oral dosage formulation according to invention may be compressed to get adequate hardness to prevent premature inflowing of the aqueous medium into oral dosage form. According to one of the main embodiment wherein hardness of tablets produced is in range of 5 Kg/cm2 to 10 Kg/cm2 or 15 Kg/cm2 or 20Kg/cm2. Oral dosage forms

produced by inventive composition having human administrable active ingredient is suitable of human use. Alternatively drug suitable for veterinary purpose formulated in accordance with present composition will be suitable for veterinary use.
According to the objective of present invention NSAIDs are formulated in oral dosage form for controlled release delivery. In an exemplary inventive formulation in accordance with invention have pharmacologically active ingredient is Diclofenac or diclofenac-Na. Inventive composition may be comprising 50 to 100 mg of diclofenac or diclofenac-Nain plurality of dosage formulations. Controlled release formulation can have more drug content than normal delivery dosages because it does not delivery all content of drug immediately thereby reducing toxic effect or other related problems.
In accordance of present invention NSAIDs formulation produced are suitable for once a day administration, more preferably once a day administration.
Following examples are offered to more fully illustrate the invention, but are not to be construed as limiting the scope thereof.
Examples
Example 1.
Ready to use composition is prepared by taking Hypromellose high viscosity (HPMC) 26% {w/w of dry weight composition) and Hypromellose low viscosity 13% (w/w of dry weight composition) weighing appropriate quantity and sieving through 40 mesh screen. Subsequently filler Lactose monohydrate 61% (w/w of dry weight composition) is weighed and sieved through 40 mesh screen. All components duly sieved are blended together in blender for 20 minutes (e.g. octagonal blender). Dry powder thus prepared is stable for storage and reusable in batches of operations,

Table 1

Sr. No. Ingredients w/wPercent(%) Grams
1. Hypromellose (HPMCK15M) USP 26 260.0
2. Hypromellose (HPMCK4M) USP 13 130.0
3. Lactose monohydrate USP 61 610.0
Total = 100 1000.0
Example 2.
Sustained release solid oral dosage formulation of Diclofenac Sodium (for 100 mg strength at 300 mg average weight) is prepared using ready to use composition of example 1,
Table 2

Sr. No. Ingredients % w/w of total dry weight
1. Diclofenac sodium 33
2. Ready to use composition 66.00
3. Solvent (IPA:water = 80:20) q.S.
4. Magnesium stearate 1.00
Total = 100
In order to get dosage formulation for Diclofenac Sodium exemplary Table 2 composition is used wherein Diclofenac Sodium is 33 % (w/w of dry weight composition) and weighed accordingly, subsequently sieved to get uniformly granulated powder through 40 mesh screen. It is noted that other size screen could be used to get similar results, Sieved Diclofenac Sodium is blended with 66% (w/w of dry weight composition) of ready to use composition in blender for 20 minutes (e.g. RMG granulator). Solvent system of IPA and Water is prepared for wet granulation procedure, wherein IPA is mixed with water in 80:20 ratio and poured in RMG granulator in low to medium speed in the duration of 10 minutes followed by 5 minutes of high speed. Generated we mass is sieved using 12 mesh screen dried in tray drier (or Fluidized bed dryer) at 60 to 65°C keeping loss on drying ar 1-2% (at 105°C for 10 minutes). Dry granules/powder are further sieved through 20 mesh screen after though tray drying process. To promote efficient tablet punching further 0.83% % (w/w

of dry weight composition) of magnesium stearate sieved through 40 mesh screen is added to above dried blended formulation in blender for subsequent 5 minutes. Granules mixed with lubricant have bulk density of about 0.35 (g/ml) and tapped density of about 0.4 (g/ml). Final screened granules are compressed using 10 mm (for 100 mg strength at 300 mg average weight) circular, biconcave punches at hardness not less than 12 kg/cm2, thickness about 3-4 mm, friability about Not more than 1 {%).
Example 3
Dissolution Profile Evaluation of tablet prepared using Ready to use composition.
A dissolution study was performed to evaluate the effect of ready to use composition with active ingredient. Drug dissolution profiles of tablet prepared are measured by USP 35 dissolution test of rotating basket method <711>. It is evident from standard state of the art that active ingredient may have its own dissolution testing parameters which can be found in their respective monographs. The active ingredient content for present invention is standardized for sustained release profile is as per table 3:-
Table 3

Time (Hour) Limit
1 15%-28%
2 20% - 40%
4 35% - 55%
5 45% - 65%
6 50% - 80%
8 52% - 82%
10 65% - 85%
16 75% - 95%
24 NLT 85%
Dissolution study was performed on Electrolab dissolution test apparatus Type 2 with experimental parameters as rpm of 50, and 900 ml of 0.05 M Phosphate buffer at pH 7.5 as dissolution medium. Time intervals for dissolution evaluation are set as 1, 5, 10, 16 and 24

hours with additional time points: 2, 4, 6 and 8 hours. For the purpose of analysis active ingredient standard was prepared by dissolving 25 mg of Dicofenac Sodium in 25 ml volumetric flask with .0.05 M phosphate buffer of pH 7.5 (100 ppm) and dilutions of 10,15, 20ppm was prepared with phosphate buffer of pH 7.5. Active ingredient absorbance was checked at 276 nm.
Solid oral dosage forms prepared are subjected to dissolution in type 2 dissolution apparatus at 50 rpm for 1, 2, 4, 6 and 10 hours of time intervals. Absorbance of solution is recorded at 276 nm on spectrophotometer. At a given time a definite amount of dissolution (5ml) solution was taken and the content of active ingredient remaining was determined. Solution withdrawn is taken in volumetric flask and volume is made up to 25 ml with 0.05 M phosphate buffer pH 7.5. Dissolution results for example batches of Diclofenac Sodium ER 100 mg tablets are given in the following table 4
Table 4

Time (Hour) Limit Example 2
01 NMT 28% 19.56
02 20% - 40% 28.66
04 35% - 60% 42.44
06 50% - 80% 63.12
10 NLT 85% 81.12
Example 4.
Another Ready to use composition is prepared by taking Hypermellose high viscosity (HPMC) 21% (w/w of dry weight composition) and Hypermellose low viscosity 19% (w/w of dry weight composition) weighing appropriate quantity and sieving through 40 mesh screen. Subsequently filler Lactose monohydrate 60% (w/w of dry weight composition) is weighed and sieved through 40 mesh screen. All components duly sieved are blended together in

blender for 20 minutes (e.g. octagonal blender). Dry powder thus prepared is stable for storage and reusable in batches of operations.
Table 5

Sr. No. Ingredients w/w Percent(%) Grams
1. Hypromellose (HPMCK15M) USP 21 210.0
2. Hypromellose (HPMCK4M) USP 19 190.0
3. Lactose 60 600.0
Total = 100 1000.0
Sustained release solid oral dosage formulation of Diclofenac Sodium (for 100 mg strength at 300 mg average weight) is prepared using ready to use composition of table 5.
Table 6

Sr. No. Ingredients % w/w of total dry weight
1. Diclofenac sodium 30
2. Ready to use composition 69
3. Solvent (IPA: water = 80:20) q.s.
4. Magnesium stearate 1.00
Total = 100
Process method and parameters of Example 2 were repeated with respective conditions to get desired dosage formulation of Table 6 composition.
Example 5.
Another Ready to use composition is prepared by taking Hypermellose high viscosity (HPMC) 30% {w/w of dry weight composition) and Hypermellose low viscosity 11% (w/w of dry weight composition) weighing appropriate quantity and sieving through 40 mesh screen. Subsequently filler Lactose monohydrate 59% (w/w of dry weight composition) is weighed and sieved through 40 mesh screen. All components duly sieved are blended together in blender for 20 minutes (e.g. octagonal blender). Dry powder thus prepared is stable for storage and reusable in batches of operations.

Table 7

Sr. No. Ingredients w/w Percent(%) Grams
1. Hypromellose (HPMCK15M) USP 30 300.0
2. Hypromellose (HPMCK4M) USP 11 110.0
Lactose monohydrate USP 59 590.0
Total = 100 1000.0
Sustained release solid oral dosage formulation of Diclofenac Sodium (for 100 mg strength at 300 mg average weight) is prepared using ready to use composition of table 7.
Table 8

Sr. No. Ingredients % w/w of total dry weight
1. Diclofenac sodium 40
2. Ready to use composition 59
3. Solvent (IPA:water = 80:20) q.s.
4. Magnesium stearate 1.00
Total = 100
Process method and parameters of Example 2 were repeated with respective conditions to get desired dosage formulation of Table 8 composition.
Example 6.
Another composition is prepared by taking Hypermellosel00M40% (w/w of dry weight composition) and Microcrystalline cellulose30% (w/w of dry weight composition) weighing appropriate quantity and sieving through 40 mesh screen. Subsequently filler Lactose monohydrate 30% (w/w of dry weight composition) is weighed and sieved through 40 mesh screen. All components duly sieved are blended together in blender for 20 minutes (e.g. octagonal blender).

Table 9

Sr. No. Ingredients w/w Percent(%) Grams
1. Hypromellose {HPMC100M) USP 40% 400
2. Microcrystalline cellulose 30% 300
Lactose monohydrate USP 30% 300
Total = 100 1000.0
Solid oral dosage formulation of Diclofenac Sodium (for 100 mg strength at 300 mg average weight) is prepared using ready to use composition of table 9.
Table 10

Sr. No. Ingredients % w/w of total dry weight
1. Diclofenac sodium 33.33
2. Table 9 composition 65.67
3. Solvent (IPA:water s 80:20) q.s.
4. Magnesium stearate 1
Total = 100
Process method and parameters of Example 2 were repeated with respective conditions to get desired dosage formulation of Table 10 composition. Subsequently in accordance with example 3 dissolution experiment was conducted and it was seen that sustained release profile is not achieved with table 10 composition.

We Claim,
1. A ready-to-use,, stable modified release composition comprising cellulosic polymer and filler for non-steroidal anti-inflammatory drugs (NSAIDs) or their pharmaceutically acceptable sate thereof.
2. A ready-to-use, stable modified release composition comprising,
a. a combination of cellulosic polymer(s) with different viscosity grades; and
b. filler.
3. A ready-to-use, stable modified release composition wherein viscosity grades are in range of 4000 cps to 20000 cps.
4. A stable modified release formulation comprising ready to use composition of claim 2 and NSAIDs or its pharmaceutically acceptable salts thereof.
5. A stable modified release formulation according to claim 4 wherein, NSAIDs is in range of 30-40 % of weight by weight of formulation.
6. A ready-to-use, stable modified release formulation comprising
a. cellulosic polymer of higher viscosity in the range of 10 to 20% weight of
formulation;
b. cellulosic polymer of lower viscosity in the range of 20 to 31% weight of
formulation;
c. filler in the range of 50 to 75% weight of formulation; and
d. NSAIDs in the range of 30 to 40% by weight of formulation.
7. A process for preparing a stable composition ready for use according to preceding
claims comprising steps of-
a. Pre-coalescing of cellulosic polymer(s) and filler
b. Thorough mixing to form dry powder
c. Wet granulation with NSAIDs and solvent
d. Sieving through appropriate size
e. Tray drying
f. Optionally, addition of lubricant
g. Final compression

8. The ready-to-use composition according to claim 1, wherein cellulosic polymer is selected from derivative of cellulose, ethyl cellulose, methyl cellulose, ethyl methyl cellulose, hydroxyethyl cellulose, hydroxy proply cellulose, hydroxy propyl methyl cellulose, hydroxyethyl methyl cellulose and ethyl hydroxyethyl cellulose.
9. The ready-to-use composition according to claim 1, wherein filler is selected from lactose, lactose monohydrate, dibasic calcium phosphate (anhydrous), microcrystalline cellulose, and further may include calcium sulphate, cellulose, kaolin, mannitol, sodium chloride, powdered sugar and dry starch.
10. A stable modified release oral dosage form of NSA1D prepared by process of claim 7.