Controlled release ibuprofen tablet formulations
FIELD OF THE INVENTION:
The present invention relates to the controlled release tablet formulation of ibuprofen. The tablet comprises fillers, binder, lubricants and glidant along with one or more controlled release polymers. The controlled release polymers used are KoUidon SR and Carbopol 971 P. The controlled release tablets of the present invention thus relates to the matrix type of formulation containing ibuprofen as active ingredient.
BACKGROUND OF THE INVENTION:
Ibuprofen is used for both acute and chronic pain. The acute pain is treated with conventional tablets, capsules, topical gels or injection dosage forms. The chronic pain however requires the administration in the form of controlled or sustained release manner. The controlled release requires the slow release of medicament over the extended period of time.
Although many sustained release formulations are known, there is no generally applicable method by which such formulations can be designed. Each formulation is dependent on the particulai' pharmaceutical incorporated therein. In designing a formulation, it is generally necessary to take into account many factors, including the rates of absorption and clearance of the pharmaceutical. the interaction of the pharmaceutical with the excipients and/or coatings to be used in the formulation, the solubility of the excipients and/or coatings, and the effects on the bioavailabilitx of the pharmaceutical which may be caused by the excipients and/or coatings. It is, however, not possible readily to predict whether any particular formulation will provide the desired sustained release, and it is generally found necessary to carry out considerable experimentation to produce a desired sustained release formulation.
In an effort to select such an ingredients to produce controlled release tablet dosage form o( ibuprofen, it has been observed that Carbopol 971 P and Kollidon SR offers some potential advantages over the prior controlled releasing excipients in use.
Accordingly it is an objective of the present invention to prepare a controlled release tablet dosage form of ibuprofen containing the Carbopol 971 P and Kollidon SR along with suitable fillers, binders, lubricants or glidant.

SUMMARY OF THE INVENTION:
The controlled release tablet formulation of the present invention was prepared by blending ibuprofen and Carbopol 971 P, granulating the blend with polyvinylpyrrolidone K-30 in isoprop\ I alcohol, passing the wet mass though mesh # 8 followed by drying. The dried granules were passed through mesh # 40 and blended for five minutes. The blend obtained above was then mixed with hydrogenated castor oil, colloidal silicon dioxide, talc and anhydrous dicalcium phosphate to obtain a lubricated blend. The lubricated blend was then compressed into tablets using suitable punches.
According to one of the embodiment of the invention the ibuprofen was granulated with polyvinylpyrrolidone K-30, The wet mass after passing through mesh # 8 was dried. The dried granules after passing through mesh # 30 were mixed with KoUidon SR, stearic acid/ hydrogenated cotton seed oil, collidal silicon dioxide, talc and anhydrous dicalcium phosphate and blended lor five minutes in suitable blender. The resulting blend was compressed into tables using suitable punches.
DETAILED DESCRIPTION OF THE INVENTION:
The present invention comprises controlled release tablet formulation of ibuprofen consisting oi^ carbopol 971 P and Kollidal SR. The controlled release tablet formulation of ibuprofen furlhcr comprises fillers, binder,lubricants, glidant. The controlled release tablet formulation of ibuprofen is in the form of matrix tablet.
The controlled release tablet formulation of ibuprofen is made in accordance with the following steps:
1. Blending ibuprofen and carbopol 971 P for 5-20 minutes.
2. Granulating the powered blend from step 1 with 5 to 9 % solution of polyvinylpyrrolidone in
Isopropyl alcohol.
3. Drying wet granules in hot air over at 45° C for about 3 to 6 hours.
4.Blending granules with filler, glidant, lubricant.
5.Compressing the lubricated granules of step 4 with drug polymer granules for 5 to 15 minutes and compressed on tablet compression machine.
The controlled release tablet formulation of ibuprofen is also made in accordance with the following steps:

1,Granulating the powered ibuprofen with 1 to 5 % solution of polyvinylpyrrolidone in Isopropyl alcohol.
2. Drying wet granules in hot air over at 45° C for about 3 to 6 hours.
3. Blending Kollidal SR, filler, glidant, lubricant for 5 minutes.
4. Lubricated blend with drug granules blended for 5 to 15 minutes and compressed on tablet compression machine.
The present invention comprises ibuprofen as active ingredient.
The present invention uses controlling polymer as Kollidon SR and Carbopol 971 P.We have been observed that Kollidon SR and Carbopol 971 P have advantageous controlled release properties. In such formulations the active ingredient is released slowly into the body over a prolonged period, and in particular allows once a daily administration of a drug to a patient.
The composition of the present invention comprises ionic crosslinked polymers like Carbopol 97IP &/or Carbopol 974P. As the gastric fluid penetrates inside the dosage form, carbopol layer hydrates forming a gel layer, which is markedly different from the gel layer formed by the other non ionic or ionic polymers. The hydrogel formed by carbopol is not a entangled chains of polymers, but a discrete micro gels made with numerous polymer particles in which the drug is entrapped. The carbopol 97IP is very lightly crosslinked and form a fishnet type gel structure upon hydration. This crosslinked site opens up easily at very low concentration of polymers & eliminates the interstitial spaces between the hydrated gel particles. This in turns forms a very uniform & homogeneous gel structure without the regions of micro viscosity and macro viscosity which are observed with almost all the other polymers & offers a resistance to the diffusion of drug particles. These polymers being non soluble in water, does not dissolve & erosion does not takes place. It is this unique character of the crosslinked polymer which helps in retarding the drug release for a longer period of time at very low concentration. When the hydrogel is fully hydrated, osmotic pressure generated by the channeling agents helps in the diffusion of drug at a continuous rate.
The gel structure of Carbopol is totally different from the other polymers like hydroxypropyl methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose etc. Because of the unique gel structure of the Carbopol, it forms a very homogeneous gelatinous skin surrounding the drug particles and retards drug release for a longer period of time at lower concentration compared to

other polymers. Other polymers show a region of microviscosity and macroviscosity in its gel structure which leads to nonuniform drug release. Whereas in Carbopol such regions are absent hence the drug release is usually uniform.
Kollidon SR is polyvinyl acetate and povidone based matrix-retarding agent. It is a white or slightly yellowish, free flowing powder. It consists of 80% polyvinyl acetate, 19% Povidone in a physical mixture. 0.8% SLS and 0.2% colloidal silica are used as a stabilizers. It is worth to mention that Kollidon SR can be successfully replaced by a mixture of polyvinyl acetate and Povidone. Since polyvinyl acetate is plastic material that produces a coherent matrix under low compression forces, when tablets are introduced into gastric or intestinal fluid, the water-soluble povidone is leached out to form pores through which the active ingredient slowly diffuses outwards.
Kollidon SR contains no ionic groups and is therefore inert to drug substances. The Sustained release properties are unaffected by ions or salts. Kollidon SR has excellent compressibility and endows tablets with enormous hardness and low friability. This is due to the combination of the very plastic polyvinyl acetate and also the binding povidone.
Controlled release formulation containing pharmaceutically active ingredient Ibuprofen are employed where it is desired to administer a drug to a patient over a prolonged period without requiring the patient to take repeated doses of the drug at short intervals.
Controlled release formulation containing pharmaceutically active ingredient Ibuprofen is in the range of about 800 mg to about 1000 mg offers various advantages over the conventional dosage form. The main advantage being reduction in dosage frequency, patient convenience, reduced side effects and maintaining the steady state level of the drug in blood. Thus withought loosing the therapeutic potential of the medication the tablet dosage form of the present invention is expected to reduce the possible side effect with the conventional dosing.
As used herein the controlled release tablet dosage form refers to the dosage form designed to release the active ingredient, ibuprofen, over an extended period of time. A particular suitable time is 24 hour since such a dosage form needs only to be taken once a day to maintain control of the condition or disease/disorder.

The fillers as used herein includes anhydrous dicalcium phosphate, com starch, rice starch, potato starch, starch 1500; cellulose or cellulose derivatives like microcrystalline cellulose, powdered cellulose, or sugar or sugar derivatives like lactose, glucose, fructose; polyhydric alcohols like mannitol, xylitol or sorbitol. The preferred filler for the purpose of present invention is anhydrous dicalcium phosphate.
The binders as used in the present invention includes polyvinylpyrrolidone, starch paste, pregelatinized starch, gelatin, acacia, xanthan gum, alginic acid or alginates, carboxymethylcellulose, hydroxypropylcellulose or hydroxypropyl methyl cellulose and such like. The preferred binder of the present invention is polyvinylpyrrolidone K 30.
The lubricants or glidants are selected from talc, colloidal silicon dioxide, hydrogenated castor oil/cotton seed oil, magnesium stearate, calcium stearate, stearic acid, fumaric acid or derivatives thereof, glyceryl behenate, sodium lauryl sulphate and such like. The preferred lubricants and glidants used in this invention are talc, coUidal silicon dioxide and hydrogenated cottonseed oil.

1. Ibuprofen and Carbopol 971 P were weighed and passed through mesh #40 and blended for
5-20 minutes.
2. Polyvinylpyrrolidone K-30 was dissolved in isopropyl alcohol using a mechanical stirrer.
3. The powder blend obtained from the step (1) was granulated with the granulating solution
obtained from the step (2).

4. The wet mass was passed through the mesh # 8. The wet granules were dried in the hot air over at 45° C for 3- 6 hours.
5. The dried granules were passed through the mesh #30.
6. Ingredients 4, 5, 6 and 7 were weighed and passed through the mesh # 40, and blended for
5 minutes.
7. The lubricant blend obtained in the step (6) was blended with the dried and sieved drug
polymer granules for 5-15 minutes and compressed on tablet compression machine using
suitable capsule shape punches.
Formulation 2:
Ibuprofen CR tablets 800 mg

1. Ibuprofen was weighed and passed through mesh #40.
2. Polyvinylpyrrolidone K-~30 was dissolved in isopropyl alcohol using a mechanical stirrer.
3. The powder obtained from the step (1) was granulated with the granulating solution
obtained from the step (2).
4. The wet mass was passed through the mesh # 8. The wet granules were dried in the hot air
over at 45° C for 3 - 6 hours.
5. The dried granules were passed through the mesh # 30.
6. Ingredients 2, 4, 5, 6 and 7 were weighed and passed through the mesh # 40, and blended for 5 minutes.
7. The lubricant blend obtained in the step (6) was blended with the dried and sieved drug granules in a poly bag for 5 - 15 minutes and compressed on a tablet compression machine using suitable capsule shaped punches.
It is worth to mention that though the wet granulation method is disclosed for the manufacturing of controlled release ibuprofen tablets of the present invention, the direct compression method can

We claim:
1. A controlled release tablet formulation of ibuprofen essentially consisting of one or more controlling Polymer further comprising atleast one filler, binder, glidant or lubricant.
2. Formulation of claim 1 wherein ibuprofen is ibuprofen or it's salts.
3.Formulation of claim 1-2 wherein controlling polymer consisting of carbopol 971 or KoUidone SR.
4. Formulation of calm 1-3 wherein filler is selected from anhydrous dicalcium phosphate, corn starch, rice starch, potato starch, starch 1500; cellulose or cellulose derivatives like microcrystalline cellulose, powdered cellulose, or sugar or sugar derivatives like lactose, glucose, fructose; polyhydric alcohols like mannitol, xylitol or sorbitol.
5. Formulation of claim 1-4 wherein binder is selected from polyvinylpyrrolidone, starch paste. pregelatinized starch, gelatin, acacia, xanthan gum, alginic acid or alginates, carboxymethylcellulose, hydroxypropylcellulose or hydroxypropyl methyl cellulose.
6. Formulation of claim 1-5 wherein the lubricants or glidants are selected from talc, colloidal silicon dioxide, hydrogenated castor oil/cotton seed oil, magnesium stearate, calcium stearate. stearic acid, fumaric acid or derivatives thereof, glyceryl behenate, sodium lauryl sulphate.
7. The controlled release tablet formulation comprising ibuprofen, essentially consisting of
carbopol 971 P or Kollidon SR and Polyvinylpyrrolidone K-30, Stearic acid/Hydrogenated
cotton seed oil. Colloidal silicon dioxide (Aerosol 200), Talc, Dicalcium phosphate anhydrous.
8.The process for the preparation of the controlled release tablet formulation consisting of
1. Blending ibuprofen and carbopol 971 P for 5-20 minutes.
2. Granulating the powered blend from step 1 with 5 to 9 % solution of polyvinylpyrrolidone in
Isopropyl alcohol.
3. Drying wet granules in hot air over at 45° C for about 3 to 6 hours.
4.Blending granules with filler, glidant, lubricant.
5.Compressing the lubricated granules of step 4 with drug polymer granules for 5 to 15 minutes and compressed on tablet compression machine.

9. The process for the preparation of the controlled release tablet formulation consisting of
1.Granulating the powered ibuprofen with 1 to 5 % solution of polyvinylpyrrolidone in
Isopropyl alcohol.
2. Drying wet granules in hot air over at 45° C for about 3 to 6 hours.
3. Blending Kollidal SR, filler, glidant, lubricant for 5 minutes.
4. Lubricated blend with drug granules blended for 5 to 15 minutes and compressed on tablet compression machine.

10. Formulation as in any claim 8-9 wherein tablet is prepared by wet granulation method or direct compression method.
11. Formulation of any one of claim 1-10 as controlled release matrix tablets.

and compressed on tablet compression machine.
9. The process for the preparation of the controlled release tablet formulation consisting of
1.Granulating the powered ibuprofen with 1 to 5 % solution of polyvinylpyrrolidone in
Isopropyl alcohol,
2. Drying wet granules in hot air over at 450 C for about 3 to 6 hours.
3. Blending Kollidal SR, filler, glidant, lubricant for 5 minutes.
4. Lubricated blend with drug granules blended for 5 to 15 minutes and compressed on tablet compression machine.

10. Formulation as in any claim 8-9 wherein tablet is prepared by wet granulation method or direct compression method.
11. Formulation of any one of claim 1-10 as controlled release matrix tablets.