DESC:

FORM 2

THE PATENTS ACT,
(39 OF 1970)
THE PATENT RULES, 2003.

COMPLETE SPECIFICATION
(SECTION 10 AND RULE 13)

STABLE PHARMACEUTICAL COMPOSITIONS OF IBUPROFEN AND FAMOTIDINE

GRANULES INDIA LIMITED
My Home Hub, 2nd and 5th Floor, 3rd Block, Madhapur, Hyderabad,
Telangana, INDIA -500 081

The following specification particularly describes the invention and the manner in which it is to be performed.
FIELD OF THE INVENTION
The present invention relates to stable pharmaceutical compositions of Ibuprofen and Famotidine in a single unit dosage form. The present invention provides process for the preparation of dosage forms of Ibuprofen and Famotidine by combining it with one or more pharmaceutically acceptable excipients. The present invention also provides single dosage form units in the form of capsule, or tablet, or tablet-in-tablet, or tablet in capsule or coated granules into capsule.

BACKGROUND OF THE INVENTION
Ibuprofen is a medication in the nonsteroidal anti-inflammatory drug (NSAID) class chemically termed as (RS)-2-(4-(2-Methylpropyl) phenyl) propionic acid and structurally represented by the following structure:

Famotidine is a histamine H2 receptor antagonist chemically termed as 3-[({2-[(diaminomethylidene)amino]-1,3-thiazol-4-yl}methyl)sulfanyl]-N-sulfamoyl propanimidamide and structurally represented by the following structure:

Non-steroidal anti-inflammatory drugs (“NSAID(s)”) are known as effective analgesics for the treatment of mild to moderate pain. While generally regarded as safe, NSAIDs can cause gastritis, dyspepsia, and gastric and duodenal ulceration. Gastric and duodenal ulceration are a consequence of impaired mucosal integrity resulting from NSAID-mediated inhibition of prostaglandin synthesis. This side-effect is a particular problem for individuals who take NSAIDs for extended periods of time, such as patients suffering from rheumatoid arthritis or osteoarthritis. The risk of developing gastric or duodenal ulceration can be reduced by cotherapy with the drug Famotidine. Famotidine blocks the action of the histamine type 2 (H2) receptor, leading to a reduction of acid secretion in the stomach. Reducing stomach acid with Famotidine during treatment with certain NSAIDs are reported to decrease incidence of gastrointestinal ulcers.
In the United States Ibuprofen and Famotidine combination dosage form is approved as oral tablets with 800 mg Ibuprofen and 26.6 mg Famotidine under the brand name DUEXIS® to Horizon pharma. Although, NSAID plus Famotidine co-therapy reduces risk of developing gastric or duodenal ulceration, such therapies are not widely used. One explanation for this observation is that patient compliance is more problematic with a regimen that requires administration of two separate dosage forms. Various efforts to develop a single unit dosage form comprising both NSAID and acid reducing agents have been made in the art.
U.S. Patent publication No. US2010297224 discloses a pharmaceutical unit dosage form, comprising- (a) a sustained release component comprising an amount of a histamine receptor antagonist effective to raise gastric pH above about 3.5; and (b) an immediate release component comprising a therapeutically effective amount of an NSAID. The present invention discloses the immediate release components of Ibuprofen and famotidine in form of tablet-in-tablet and trilayered concept, hence present invention discloses the idea completely different form the above prior art.
U.S. Patent No. 8,067,033 discloses a pharmaceutical composition comprising a first portion that comprises 800 mg Ibuprofen and a second portion that comprises 26.6 mg Famotidine, wherein the surface area of direct physical contact between Ibuprofen and Famotidine does not exceed 130 mm2.
U.S. Patent No. 8,067,451 discloses a pharmaceutical composition in tablet form comprising a first portion that comprises 800 mg Ibuprofen and a second portion that comprises 26.6 mg Famotidine, wherein a barrier layer comprising hydroxyl propyl methyl cellulose 2910, polyoxyethylene glycol 400, polysorbate 80, and titanium dioxide surrounds the second portion completely separating it from the first portion
U.S. Patent No. 8,309,127 discloses a pharmaceutical composition comprising: a first layer comprising from 750 mg to 850 mg Ibuprofen as an active pharmaceutical ingredient and a second layer comprising from 24 mg to 28 mg Famotidine as an active pharmaceutical ingredient, provided that the composition is a table-in-tablet formulation, with first layer completely surrounding the second layer,
International (PCT) Patent publication No. WO 2008/091957 discloses a pharmaceutical composition comprising: a) Ibuprofen-containing particles, wherein at least 80% of the Ibuprofen particles are retained by 60 mesh screen and not more than 5% of the Ibuprofen particles are retained by 20 mesh screen, and b) Famotidine- containing particles, wherein at least 80% of the Famotidine-containing particles are retained by 60 mesh screen and not more than 5% of the Famotidine-containing particles are retained by 20 mesh screen wherein the ratio of Ibuprofen to Famotidine (w/w) is at least 20.
U.S. Patent publication No. US 2005/0020671 discloses a pharmaceutical formulation which comprises a core with first active ingredient, a coating comprising a second active ingredient incompatible with the first active ingredient and a barrier between the core and the coating preventing physical contact between the core and the coating, characterized in that the barrier is formed on the core by film-coating and the coating is formed on the barrier by press-coating.
International (PCT) Patent publication No WO2013/054352 disclose a pharmaceutical composition in a single unit dosage form comprising a core containing Ibuprofen or salt thereof; and a surrounding portion comprising Famotidine or salt thereof in direct physical contact with the core.
The present invention discloses the ibuprofen and famotidine in tablet-in-tablet form, wherein the first portion comprises about 18.6 mg to 22.6 mg of Famotidine and Second portion comprise 800 mg of Ibuprofen and about 4 mg to 8 mg of Famotidine. The present invention also describes a trilayer tablet composition with first layer comprising Ibuprofen, third layer comprising Famotidine and second or middle placebo layer separating both the Ibuprofen and Famotidine layers. Hence present invention discloses the idea different form the above said prior arts.
Ibuprofen and Famotidine react chemically with each other to produce degradation products. The reaction becomes a serious stability problem for pharmaceutical compositions containing both active ingredients. Various attempts have been made in the past to combine both the active ingredients. However, still there exists a need to develop an ideal formulation, which is more simplified, enabling the simple production of the composition and exhibiting exceptional stability
It has been surprisingly found by the inventors that pharmaceutical compositions of Ibuprofen and Famotidine according to present invention were found to be simple, cost effective, stable and exhibited desired bioavailability which was also found to be comparable with the marketed formulation.
The inventors of the present disclosure also speculate that for a prescriber and also to a manufacturer to make/ or rather to prescribe and to make affordable in terms of providing the direct generic combination of Ibuprofen and Famotidine. However the inventors of the present disclosure surprisingly found in same terms of affordability to patients and also to manufacturer in terms of yield and in whole a pretty simple dosage form circumventing the complexity existing the marketed dosage form to manufacturer by saving the manufacturing cost as well.

SUMMARY OF INVENTION
Particular aspect of the present invention provides a stable pharmaceutical composition in a single dosage form comprising Ibuprofen, Famotidine and manufacturing methods thereof.
One aspect of the present invention relates to stable pharmaceutical composition in a compressed dosage form comprising Ibuprofen, Famotidine and one or more pharmaceutically acceptable excipients.
In another aspect of the present invention relates to trilayer pharmaceutical composition in the form of a sandwich structure includes first layer containing Ibuprofen, second or middle placebo layer, and third layer containing Famotidine, where in the placebo layer is a middle one separating both the Ibuprofen and Famotidine layers.
In another aspect of the present invention relates to tablet-in-tablet pharmaceutical composition comprising inner core and outer shell, where in the Famotidine is present both in inner core and outer shell.
In another aspect of the present invention relates to tablet-in-tablet pharmaceutical composition comprising an inner core with Famotidine in an amount of 70-85% w/w of total Famotidine in the dosage form and an outer shell surrounding the inner core comprising Ibuprofen and remaining 15-30% w/w of total Famotidine in the dosage form, where in the amount of Ibuprofen present in the dosage form is 800 mg and total amount of Famotidine present in both inner core and outer shell is 26.6 mg.
In another aspect the present invention relates to a capsule dosage form comprising compressed tablets of Ibuprofen and Famotidine.
In yet another aspect the present invention relates to capsule dosage form comprising granules or pellets of Ibuprofen and Famotidine.
In yet another aspect the present invention also relates process for preparing the compositions thereof.
Further particular aspects of the invention are detailed in the description part of the specification, wherever appropriate.

DETAILED DESCRIPTION
As set forth herein, embodiments of the present invention provide stable pharmaceutical composition in a single dosage form comprising Ibuprofen, Famotidine and at least one additive.
Accordingly, the present invention provides single dosage form units in the form of capsule, or tablet, or tablet-in-tablet, or tablet in capsule or coated granules into capsule.
In one embodiment the present invention provides stable pharmaceutical composition in a compressed dosage form comprising Ibuprofen, Famotidine and one or more pharmaceutically acceptable excipients.
In one embodiment according to present invention the compressed dosage form is a trilayer tablet composition.
Accordingly the tri-layer tablet comprise a first layer of Ibuprofen or its pharmaceutically acceptable salts; another layer of Famotidine or its pharmaceutically acceptable salts and a barrier or placebo layer present in between both the Ibuprofen and Famotidine layers.
Accordingly, the trilayer tablet comprise first layer containing Ibuprofen and one or more pharmaceutically active excipients, second or middle placebo layer containing one or more pharmaceutically acceptable excipients separating both the Ibuprofen and Famotidine layers and finally third layer containing Famotidine and one or more pharmaceutically active excipients.
In a preferred embodiment, according to present invention the first layer comprise about 800 mg of Ibuprofen or its pharmaceutically acceptable salts with suitable pharmaceutically acceptable excipients, middle placebo layer is free of any active ingredients and comprise one or more pharmaceutically acceptable excipients and third layer comprise about 26.6 mg of Famotidine or its pharmaceutically acceptable salts with suitable pharmaceutically acceptable excipients.
Accordingly one or more pharmaceutically excipients are selected from diluents, binders, disintegrants, polymers, glidants, lubricants and the like.
In another particular embodiment the present invention provides a process for preparing compressed dosage form in the form of trilayer tablets comprising the steps of:
(a) Preparation of First Ibuprofen layer separately by combining Ibuprofen with one or more pharmaceutically acceptable excipients (b) Preparation of second placebo layer by combining one or more pharmaceutically acceptable excipients (c) Preparation of third Famotidine layer by combining Famotidine with one or more pharmaceutically acceptable excipients and finally (d) loading all the layers separately in to compression machine to form trilayer tablet.
In another embodiment, according to the present invention it relates process for preparation of pharmaceutical composition by direct compression, dry granulation or wet granulation method.
In another embodiment, according to the present invention each layer of the tablet is prepared by direct compression, dry granulation or wet granulation method.
In another embodiment according to present invention the compressed dosage form is tablet-in-tablet composition.
In yet another embodiment tablet-in-tablet composition comprise inner core with Famotidine in an amount of 70-85% w/w of total Famotidine in the dosage form and an outer shell surrounding the inner core comprising Ibuprofen and remaining 15-30% w/w of total Famotidine in the dosage form.
In yet another embodiment according to present invention the amount of Ibuprofen present in the outer shell is about 800 mg and total amount of Famotidine present in both inner core and outer shell is about 26.6 mg.
In a preferred embodiment, according to present invention the inner core contains Famotidine in an amount of about 18.6 mg to 22.6 mg and outer shell comprises about 4 mg to 8 mg of Famotidine.
In a more preferred embodiment according to present invention, tablet-in-tablet composition comprise first component of inner core with 70-85% w/w of total Famotidine or its pharmaceutically acceptable salts in the dosage form with suitable pharmaceutically acceptable excipients and a second component of outer shell surrounding the inner core comprising Ibuprofen or its pharmaceutically acceptable salts and remaining 15-30% w/w of total Famotidine in the dosage form with suitable pharmaceutically acceptable excipients, wherein the amount of Ibuprofen present in the dosage form is 800 mg and total amount of Famotidine present in both inner core and outer shell is 26.6 mg.
In one embodiment the tablet-in-tablet composition is produced by first preparing a core tablet from a first component, and then applying a tablet shell through compression of a second component in a manner such that the finished formulation comprises the core surrounded by the shell.
In another particular embodiment according to the present invention first component comprise 70-85% w/w of total Famotidine or its pharmaceutically acceptable salts with one or more pharmaceutically acceptable excipients and second component comprise Ibuprofen or its pharmaceutically acceptable salts and remaining 15-30% w/w of total Famotidine with one or more pharmaceutically acceptable excipients.
In another embodiment, according to the present invention it relates process for preparation of tablet composition by direct compression, dry granulation or wet granulation method.
In another aspect the present invention relates to a capsule dosage form comprising compressed dosage forms of Ibuprofen and Famotidine.
In another embodiment according to the present invention the capsule dosage form comprise granules, pellets or minitablets of Ibuprofen and Famotidine filled in to capsule.
In another embodiment according to the present invention the capsule dosage form is produced by first preparing single unit dosage forms of Ibuprofen and Famotidine with one or more pharmaceutically acceptable excipients and then filling it in to a capsule.
In another embodiment according to the present invention relates process for preparation of unit compositions by direct compression, dry granulation or wet granulation method.
Accordingly, one or more pharmaceutically excipients are selected from diluents, binders, disintegrants, polymers, glidants, lubricants and the like
In yet another embodiment the compressed tablets may be coated with one or more polymer coatings.
According to any of the embodiment’s one or more pharmaceutically excipients are selected from diluents, binders, disintegrants, polymers, glidants, lubricants and the like.
Suitable "diluents" include, but are not limited to, either individually or in combination, microcrystalline cellulose, lactose, starch, corn starch, pregelatinized starch, maize starch, potato starch, powdered celluloses, sorbitol, xylitol, dibasic calcium phosphate, calcium phosphate, calcium carbonate, magnesium carbonate and the like.
Suitable "binders" include, but are not limited to, either individually or in combination, lactose, starches such as corn starch, potato starch, modified starches, sugars, guar gum, pectin, wax binders, microcrystalline cellulose, methylcellulose, carboxymethylcellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, copolyvidone, sodium alginate, acacia, alginic acid, tragacanth, carboxymethylcellulose sodium, ethyl cellulose, gelatin, liquid glucose, povidone and pregelatinized starch, and the like or mixtures thereof
Suitable "disintegrants" include, but are not limited to, either individually or in combination, sodium starch glycolate, croscarmellose sodium, polacrilin potassium, crospovidone, pregelatinized starch and the like.
Suitable "glidants" include, but are not limited to, either individually or in combination, colloidal silicon dioxide, talc, magnesium silicate, magnesium trisilicate, and other forms of silicon dioxide, such as aggregated silicates, hydrated silica and the like.
Suitable "lubricants" include, but are not limited to, either individually or in combination, glyceryl distearate, talc, magnesium stearate, stearic acid, fumaric acid, palmitic acid, sodium stearyl fumarate, carnauba wax, hydrogenated vegetable oils, mineral oil, polyethylene glycols and the like.
The term “stable,” as used herein, refers to a composition in which the active pharmaceutical ingredients (i.e., ibuprofen and/or famotidine) are present in an amount of at least 90%, and preferably at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% of the originally specified amount for each such ingredient, and no more than 3%, and preferably no more than 2%, no more than 1%, no more than 0.9%, no more than 0.8%, no more than 0.7%, or no more than 0.6% sulfamide is present after a specified period of time and under specified conditions.
The invention is further exemplified with following examples which are not intended to limit the scope of the invention.

EXAMPLES:
The following examples further describe and demonstrate particular embodiments within the scope of the present invention. It will be apparent to those skilled in the art that many modifications, both to materials and methods, may be practiced without departing from the scope of the invention.

Table 1: EXAMPLE-1 Tablet-in-tablet composition
Tablet shell
Item Material % w/w mg/Tab
1 Ibuprofen 87.8% 800.0
2 Famotidine 0.44 4.0
3 Microcrystalline cellulose 5.76 52.48
4 Pregelatinized starch 1.8 16.40
5 Povidone (K – 90) 0.3 2.73
6 Croscarmellose Sodium 3.0 27.33
7 Magnesium stearate 0.4 3.64
8 Colloidal Silicon Dioxide 0.5 4.55
9 Purified water Q.S Q.S
Total 100.00 911.13

Manufacturing process:
1. Binder solution is prepared by mixing povidone in purified water
2. Ibuprofen, pregelatinised starch and microcrystalline cellulose are loaded into Rapid Mixer Granulator and granulated using binder solution to form wet granules.
3. The obtained wet granules were dried milled, sifted and blended with Famotidine, croscarmellose sodium and colloidal silicon dioxide to form a blend for tablet shell.
4. The granules of step (3) were finally lubricated with magnesium stearate.

Table 2: Core tablet
Item Material % w/w mg/Tab-in-Tab
1 Famotidine 28.46 22.6
2 Lactose monohydrate 13.35 10.6
3 Microcrystalline cellulose 50.37 40.0
4 Croscarmellose sodium 6.29 5.0
6 Magnesium stearate 1.52 1.2
Total 100.00 79.4

Manufacturing process:
a) Famotidine, lactose, microcrystalline cellulose and croscarmellose sodium were sifted and blended.
b) The obtained blend was lubricated with magnesium stearate
c) The lubricated blend of step (b) was compressed to form a tablet (i.e., a Famotidine core) on a rotary tablet press.

Compression into Tablet in Tablet with Tablet Shell of Lubricated Ibuprofen granules and Core Tablet

Table 3:
S. No Name of the Ingredient For 800/26.6 mg
Qty/unit (mg)
1 Tablet Shell of Lubricated Ibuprofen granules 911.13 mg
2 Core Tablet 79.40 mg
Total Weight 990.53 mg

Manufacturing process:
a) The Famotidine core tablet is then centered in a tablet-in-tablet composition by compressing 911.13 mg of Ibuprofen granules around the Famotidine core using a tablet press.

Table 4: EXAMPLE-2 Trilayer tablet composition
Item Material % w/w mg/Tab
First layer
1 Ibuprofen 80.0 800.0
2 Microcrystalline cellulose 4.25 42.48
3 Povidone (K – 90) 0.27 2.73
4 Croscarmellose Sodium 1.73 17.33
5 Magnesium stearate 0.36 3.64
6 Purified water Q.S Q.S
Middle placebo layer
1 Lactose monohydrate 4.4 44.0
2 Povidone 0.20 2.0
3 Sodium starch glycolate 0.74 7.4
4 Magnesium stearate 0.21 2.1
Third Famotidine layer
1 Famotidine 2.66 26.6
2 Lactose monohydrate 1.06 10.62
3 Microcrystalline cellulose 3.3 32.9
4 Croscarmellose sodium 0.6 6.0
5 Magnesium stearate 0.22 2.2
6 Purified water Q.S Q.S
Total 100 1000

Manufacturing process:
Preparation of First Ibuprofen layer:
1. Binder solution was prepared by mixing povidone in purified water
2. Ibuprofen, microcrystalline cellulose and croscarmellose sodium were sifted, blended and granulated using binder solution to form wet granules.
3. The obtained wet granules were milled, dried, sifted and finally lubricated with magnesium stearate to form a blend for First Ibuprofen layer
Preparation of Middle Placebo layer:
1. Lactose, povidone and sodium starch glycolate were sifted separately, blended and finally lubricated with magnesium stearate to form a blend for placebo layer.

Preparation of Third Famotidine layer:
1. Famotidine, lactose, microcrystalline cellulose and croscarmellose sodium were sifted and blended.
2. The obtained blend was lubricated with magnesium stearate to form a blend for third Famotidine layer
Compression:
Blend of all the three layers were loaded separately in to compression machine with first Ibuprofen layer, middle placebo layer and third Famotidine layer and compressed to form a trilayer tablet
Stability Studies:
“Forced degradation” conditions (e.g., 40° C. and 75% relative humidity) are used to evaluate the long-term storage stability of a pharmaceutical ingredient or composition. Trilayer Tablet and Tablet-in-Tablet Compositions of the present invention are stable for extended periods under “forced degradation” conditions of elevated temperature and relative humidity.
In general terms, a stable composition is one which comprises the pharmaceutically active ingredients in an amount, for example 95%, relative to the amount initially present in the particular composition. Stability may be determined, using forced degradation or other methods, for periods of 1 week, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 9 months, 12 months, 15 months, 18 months, 24 months, 30 months, 36 months, longer.
Stability may also be determined by the presence and quantity of impurities. A principal degradant produced through the chemical interaction of famotidine and ibuprofen in compositions of the present invention is sulfamide. A quantitative determination of the presence of sulfamide in a unit dose form of the present invention held under forced degradation conditions for a period of time yields valuable information about the long-term stability of the composition under ordinary (e.g., room temperature) storage conditions.
Assays for evaluating the stability of a pharmaceutical composition, such as those described in the present invention, are known in the pharmaceutical arts. For example, one can determine the percentage of active pharmaceutical ingredients present in a given composition, as well as the presence and percentage of impurities, through the use of standard analytical techniques.
Stability of two distinct famotidine plus ibuprofen formulations of Example 1 (Tablet-in-tablet composition) and Example 2 (Trilayer tablet composition) were evaluated under “forced degradation” conditions of 40° C. and 75% relative humidity to assess the viability of the different combinations of the active pharmaceutical ingredients. Surprisingly, the formulations in accordance with the present invention exhibited stability, as shown in Table 5 below:
Table 5: Stability data
6 Month Stability of Famotidine + Ibuprofen Compositions
(@ 40° C. and 75% Relative Humidity)
Stability Indicator Tablet-in-tablet Trilayer tablet
% Sulfamide 0.60 0.45
Ibuprofen Impurities** 0.01 0.02
Total Impurities 0.70 0.53
% Ibuprofen* 100 100
%Famotidine* 96 96.5
*Calculated from initial sample assessment; each formulation includes 26.6 mg famotidine and 800 mg ibuprofen.
**Ibuprofen impurities comprise components attributable to the degradation of ibuprofen.
While the foregoing pages provide a detailed description of the preferred embodiments of the invention, it is to be understood that the summary, description are illustrative only of the core of the invention and non-limiting. Furthermore, as many changes can be made to the invention without departing from the scope of the invention, it is intended that all material contained herein be interpreted as illustrative of the invention and not in a limiting sense.

Dated this 20th day of Aug 2019
Signature: Dr. Vure Prasad
HEAD Corporate- IP
Granules India Ltd.

PHARMACETICAL COMPOSITIONS OF IBUPROFEN AND FAMOTIDINE
ABSTRACT
The present invention relates to stable pharmaceutical compositions of Ibuprofen and Famotidine in a single unit dosage form. The present invention also provides trilayer tablet and tablet-in-tablet dosage forms comprising Ibuprofen and Famotidine. It also relates to process for the preparation of dosage forms by combining Ibuprofen and Famotidine with at least one additive and turning down to a unit dosage form wherein , the unit dosage form can be capsule, tablet-in-tablet and tablets in capsule, separate coated granules filled into capsule.

Dated this 20th day of Aug 2019
Signature:


Dr. VURE PRASAD
Patent Agent Reg. No.: IN/PA-1636
HEAD-Global IP, Granules India Ltd.

,CLAIMS:We claim:
1. A pharmaceutical composition in the form of trilayer sandwich structure comprising:
a. A first layer comprising Ibuprofen and one or more pharmaceutically acceptable excipients
b. A second or middle placebo layer comprising one or more pharmaceutically acceptable excipients and
c. A third layer comprising Famotidine and one or more pharmaceutically acceptable excipients
Wherein the second or middle placebo layer separates both the Ibuprofen and Famotidine layers.
2. A pharmaceutical composition according to claim 1, where in the first layer comprise about 800 mg of Ibuprofen or its pharmaceutically acceptable salts and third layer comprise about 26.6 mg of Famotidine or its pharmaceutically acceptable salts, wherein the second or middle placebo layer is free of any active ingredients.
3. A pharmaceutical composition according to claim 1, where in one or more pharmaceutically excipients are selected from diluents, binders, disintegrants, polymers, glidants, lubricants and the like.
4. A pharmaceutical composition according to claim 1, where in the pharmaceutical composition is a trilayer tablet.
5. A process for preparing trilayer tablet composition of claim 4, where in the process comprise the steps of: (a) Preparation of First Ibuprofen layer separately by combining Ibuprofen with one or more pharmaceutically acceptable excipients (b) Preparation of second placebo layer by combining one or more pharmaceutically acceptable excipients (c) Preparation of third Famotidine layer by combining Famotidine with one or more pharmaceutically acceptable excipients and finally (d) loading all the three layers separately in to compression machine to form trilayer tablet.
6. A process for preparing trilayer tablet composition according to claim 5, where in each layer of the tablet is prepared by direct compression, dry granulation or wet granulation.
7. A pharmaceutical composition in the form of tablet-in-tablet composition comprising
a) A first component of inner core comprising 70-85% w/w of total Famotidine in the dosage form and one or more pharmaceutically acceptable excipients
b) A second component of outer shell surrounding the inner core comprising Ibuprofen, remaining 15-30% w/w of total Famotidine in the dosage form and one or more pharmaceutically acceptable excipients.
Wherein the amount of Ibuprofen present in the dosage form is 800 mg and total amount of Famotidine present in both inner core and outer shell is 26.6 mg.
8. A pharmaceutical composition according to claim 7, where in one or more pharmaceutically excipients are selected from diluents, binders, disintegrants, polymers, glidants, lubricants and the like.
9. A pharmaceutical composition according to claim 7, where in the tablet-in-tablet composition is produced by first preparing a core tablet from a first component, applying a tablet shell through compression of a second component in a manner such that the finished formulation comprises the core surrounded by the shell.
10. A pharmaceutical composition according to claim 7, where in the tablet-in-tablet composition is prepared by direct compression, dry granulation or wet granulation.

Dated this 20th day of Aug 2019

Signature:


Dr. VURE PRASAD
Patent Agent Reg. No.: IN/PA-1636
HEAD-Global IP, Granules India Ltd.