FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
THE PATENT (AMENDMENT) RULES, 2006
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION
Novel Pharmaceutical Compositions Of Antiflatulent With Antacids And Process
For Preparing The Same
2. APPLICANT
(a) NAME : Troikaa Pharmaceuticals Limited
(b) NATIONALITY : IN
(c) ADDRESS : Commerce House-1, Satya Marg, Bodakdev, Ahmedabad-380054,
Gujarat, India
3. PREAMBLE TO THE DESCRIPTION
COMPLETE
The following specification particularly describes the nature of this invention and the manner in which it is to be performed: -

FIELD OF THE INVENTION
The present invention relates to compressed oral pharmaceutical compositions. More particularly, it relates to novel compositions comprising a therapeutically effective amount of one or more antacids and antiflatulents, process for preparing the same and a method of use of such compositions,
BACKGOUND OF THE INVENTION
Hydrochloric acid is secreted from the walls of the human stomach which is necessary for the digestion of food. When the stomach contains an excessive amount of hydrochloric acid, then the condition is called as hyperacidity or acid dyspepsia. If the condition remains untreated for a long period of time it leads to various kinds of stomach ailments such as Stomach Ulcers, and Acid Reflux Disease. Often, the condition of hyperacidity is associated with flatulence and needs a treatment with quick therapeutic action. Therefore, the combinations of antacids with antiflatulents are commonly used for the treatment of hyperacidity and flatulence. A combination of various antacids with simethicone are know in the art and these formulations in the prior art are manufactured as compressed tablets that needs be chewed or in the form of thick suspensions.
There are various references disclosing the compositions of simethicone adsorbed on a solid carrier in order to easily incorporate them in different dosage forms with or without additional active ingredients.
Such compositions with simethicone adsorbed on an inert adsorbent material in different ratios are known in the art. U.S.Pat.No.4,906,478 discloses an antigas and/or antiflatulent composition comprising an admixture combinate of liquid simethicone and powdered calcium silicate. The simethicone and calcium silicate are blended and sheared to assure a uniform free-flowing powder combinate of less than 50 micron particle size. The simethicone and calcium silicate are preferably present in equal amounts by weight. Excipients may be blended with the powdered combinate and prepared in a unit dose in the form of a compressed tablet or powder-filled capsule.
Similarly, U.S.Pat.No.6, 103,260 relates to an antifoam oral solid formulations the from of a free flowing granular composition comprising an admixture of simethicone and either one or both of granular anhydrous tribasic calcium phosphate or dibasic calcium phosphate wherein the admixture is a uniform granular composition of not more than 1000 micron particle size which is suitable for compression into a solid dosage form for oral administration.

U.S.Pat.No.6,793,934 discloses solid pharmaceutical composition comprising a solid carrier containing one or more liquid ingredients such as liquid active agents, absorption enhancer, or solubility enhancers. The patent includes simethicone as one of the said active agent and Magnesium aluminometasilicate as a carrier. It is clear form the disclosure that the compositions are intended to incorporate a liquid ingredient in a solid dosage form and dose not teach anything about preparing a rapidly disintegrating formulation while combining Simethicone with an antacid such as Magaldrate.
WO/2008/056200 discloses an oral pharmaceutical composition that includes simethicone, a pharmaceutically acceptable salt of silicate, at least one adsorbent material that adsorbs simethicone, and optionally one or more pharmaceutically acceptable excipients. The reference discloses a laundry list of active ingredients that can be combined with simethicone and does not throw light on achieving rapid disintegration of the formulation in mouth upon sucking / minimum chewing the formulation. It is clear form the disclosed formulations that the main focus of the reference is to prepare a formulation that can be either chewed or swallowed.
U.S. Pat.No.7, 691,409 provides a composition for forming a compressed solid dosage form that is a free-flowing compressible admixture of simethicone, an adsorbent, and an optional active agent, wherein the weight ratio of simethicone to adsorbent is at least 1: 2.22. Also included are solid dosage forms made from a free-flowing compressible admixture of simethicone, an adsorbent, and an optional active agent, wherein the weight ratio of simethicone to adsorbent is at least 1:2.22. The patent generically discloses a list of additional active ingredients that can be included in the formulation and states that by maintaining the ratio in the said limit a formulation of nearly same or lesser in size can be achieved as compared to the formulations with lesser simethicone weight percentages. It is important to note that the patent does not address the issue of hardening of compressed formulation in case of combination of antiflatulents such as Simethicone and antacids such as Magaldrate and therefore does not disclose or provide teachings for achieving rapid disintegration of such formulations throughout the shelf life.
EP patent 00,03,589 discloses dispersible antacid formulations comprising one or more antacids in an amount of 50 to 90% and from 5 % to 15% by weight of a disintegrating agent. The patent focuses on the formulations of one or more antacids. The reference mentions in one of the examples that the formulation may include an anti-flatulent agent such as simethicone in order to prepare a tablet formulation by using a conventional process detailed in the example. The patent discloses that the approximate weight of the tablet is around 900 mg and the typical example disclosing the combination of antacid to antiflatulent is more than 770 mg. Based on the example it is apparent that the amount of

antacids that can be incorporated in a given weight of the tablet is less in comparison with the amount of other ingredients of the tablet. Therefore, it is clear that such formulations provide lesser acid neutralizing capacity as compared to the formulations having relatively high amount of antacids as compared to the other ingredients of the formulation.
The products for the treatment of hyperacidity and flatulence are desired to be available in a dispersed form in the stomach for better therapeutic action. Hence, they are available either in the form of hard chewable tablets or suspensions. It is well known that tablet formulations are more suitable as compared to suspensions due to ease of handling as well as administration. While using the chewable tablets, the patients are advised to chew the tablet properly to ensure that they break down in to small particles because if the tablet is not chewed completely, large size particles of the tablets reach the stomach where they do not provide the desired rapid action due to the formation of agglomerates of larger particles having very high hardness. In contrast, the suspensions are in liquid form and the active agents are readily available in a dispersed form once administered. However, the suspensions are associated with the problems of caking on storage, bulkiness while handling and uneven dose distribution if not properly agitated by the patients. Moreover, both of these formulations produce chalky taste in the mouth and therefore cause unpleasant feeling in the patients.
Another major disadvantage of the antacid formulations containing antiflatulent agents is the increase in the disintegration time of the on storage. Due to the nature of the composition comprising antacids in combination with antiflatulents such as simethicone, the disintegration time of the formulations increase steadily upon storage during the shelf life and crosses the acceptable limit of 15 minutes for swallowable tablets according to the Indian Pharmacopeia. Therefore, it is very difficult to achieve uniform dispersion of the active ingredients in mouth with minimum chewing or sucking of the formulation as well as to provide rapid disintegration of the tablet in the stomach when swallowed directly in order to provide rapid therapeutic action without causing unpleasant taste throughout the shelf life of the tablet.
None of the formulations of the prior art either disclose or teach the antacid formulations in combination with antiflatulents which throughout the shelf life, disperse rapidly without producing chalky taste in mouth if sucked/chewed mildly and if swallowed without chewing provide rapid therapeutic action due to negligible disintegration time in the stomach and at the same time provide higher acid neutralization capacity by maintaining a size of the tablet that can be either sucked/chewed mildly or swallowed directly without chewing.

Hence, there is a need for pharmaceutical compositions such as tablets of one or more antacids along with anti-flatulents, which upon minimum chewing, rapidly disperses in the mouth to a pleasant tasting, flavored suspension of fine particles, without any large agglomerates. On the other hand, when the same compositions are swallowed without chewing, they rapidly disintegrate in the stomach to provide the desired therapeutic benefits/effects. The formulations need to be designed in such a way that the disintegration time through out the shelf life is maintained within the acceptable limit and at the same time the use of a large quantity of excipients is avoided in order to achieve smaller/swallowable size of the formulation. Hence, there still exists a need to provide such stable compressed formulations of one or more antacids with antiflatulents that can be easily and inexpensively manufactured.
OBJECTS OF THE INVENTION:
The main object of the invention is to provide oral formulations of antacids and antiflatulents and process for preparation thereof.
Another object of the invention is to provide formulations that disperse rapidly if sucked/chewed mildly and if swallowed without chewing, provide rapid therapeutic action due to rapid disintegration in the stomach.
Another object of the invention is to provide formulations that disperse rapidly if sucked/chewed mildly without producing larger agglomerates or chalky taste in mouth.
Another object of the invention is to provide oral formulations with disintegration time (DT) maintained in the acceptable limit throughout the shelf life of the formulation.
Another object of the invention is to provide stable oral formulations with therapeutically effective amount of antacid as well as antiflatulents without allowing interaction of the components that can result in the impairment of the therapeutic activity of any one of the components or the formulation properties.
Another object of the invention is to provide oral formulations of antacid in combination with antiflatulents such as simethicone wherein the antiflatulents is adsorbed on a silicate adsorbent in such way that the formulations disintegrate rapidly if sucked/chewed mildly or swallowed without chewing. At the same time, the size/weight of the formulations is maintained in such a way that they can be easily swallowed if desired.

Another object of the invention is to provide rapidly disintegrating oral formulations of antacids and antiflatulents comprising effective amount of pharrnaceutically acceptable excipients such as disintegrating agents, binders, diluents, glidant, preservatives, flavoring agents and coloring agents.
Another object of the invention is to provide rapidly disintegrating oral formulations of antacids in combination with antiflatulents wherein, for given weight of the formulations the ratio of the amount of antacid to the amount of other ingredients of the formulations including the antiflatulents is selected in such a way that high acid neutralizing capacity of the formulations is achieved without significantly increasing the size of the formulations.
Another object of the present invention is to provide rapidly disintegrating oral formulations of antacids and antiflatulents wherein the high acid neutralizing capacity of the formulations is achieved by selecting the antacid to other excipients ratio for an appropriate dose of the antacids that needs to be included in the formulations and at the same time maintain acceptable size of the formulations that can be either chewed/sucked or swallowed without chewing.
Another object of the invention is to provide rapidly disintegrating oral formulations of antacids and antiflatulents comprising the therapeutically effective amount of antacids, antiflatulents, and minimum quantity of the pharrnaceutically acceptable excipients in order to maintain a smaller/easy to swallow size and shape of the tablet.
Another object of the invention is to provide formulations that can be prepared by a process which enables incorporation of requisite quantities of antiflatulent in formulae comprising antacid to provide free-flowing compressible granules which can be compressed in to tablets. The formulations disperse rapidly to provide a fine dispersion of the active constituents with minimum chewing in the mouth as well as disintegrate rapidly in the stomach, when swallowed without chewing throughout the shelf life of the formulation.
DESCRIPTION OF THE INVENTION
Conditions such as hyperacidity are often associated with flatulence and for the treatment of these conditions the use of combination of one or more antacids and antiflatulents is widely known. Antacid formulations either alone or in combination with antiflatulents are known to be available in the form of a suspension or chewable tables due to the larger size and higher hardness of the tablets.

As disclosed above these formulations impart several disadvantages related to patient compliance, therapeutic efficacy as well as consistency in the performance of the formulation through out the shelf life.
The present invention meets the above-mentioned and other needs by providing compressed dosage forms of therapeutically effective amount of one or more antacids with anti-flatulent, having unique feature, wherein such formulations disperse rapidly with minimum chewing or sucking in the mouth as well as disintegrate rapidly in the stomach, when swallowed without chewing, resulting in prompt therapeutic action of antacids, anti-flatulent in the treatment of hyperacidity and flatulence. Accordingly, such tablets will provide the desired therapeutic response through out the shelf life not just, when sucked or chewed mildly but even when swallowed directly without chewing.
One of the advantages that the formulations made in accordance with the present invention offer is that they disperse into fine particles upon minimum chewing. In contrast, the conventional chewable tablets comprising antacids and anti-flatulent have to be chewed adequately by the patients to ensure that upon mastication the tablet break down initially into large fragments and thereafter gradually upon persistent chewing further break down in to smaller particles. Therefore, if the patients in a hurry fails to chew the conventional chewable tablet of antacids with anti-flatulent adequately, the therapeutic response will be delayed.
Another advantage of the formulations made in accordance with the present invention is that such formulations as disclosed disintegrates rapidly to fine particles, even when swallowed without chewing. This feature of the formulations comprising one or more antacids with anti flatulent provides the rapid therapeutic action when swallowed. Moreover, if the formulations are placed in the oral cavity and sucked/chewed mildly it enables the patients to take the dose without producing chalkiness in the mouth.
The formulation of present invention further advantageously provide stable oral formulations with herapeutically effective amount of antacid as well as antiflatulents without allowing interaction of the Components that can result in the impairment of the therapeutic activity of any one of the components, vloreover, the formulation characteristics such as hardness, disintegration time etc. of the formulation prepared in accordance with the present invention are reproducible through out the shelf life of the Product.
n one of the embodiments, the present invention provides an oral pharmaceutical tablet dosage form

comprising an anti-flatulent such as simethicone/dimethicone, one or more antacids such as Magaldrate or aluminum hydroxide, at least one silicate adsorbent material that adsorbs simethicone and optionally one or more pharmaceutically acceptable excipients such as disintegrating agents, binders, diluents, glidant, preservatives, flavoring agents and coloring agents.
The said adsorbents may be selected from various grades of Neucillin, Zeopharm and pharmaceutically acceptable salts of silicate, like calcium silicate, colloidal silicon dioxide, and hydrophobic colloidal silica or combination thereof. More preferably the adsorbent material that adsorbs simethicone is magnesium aluminometasilicate (NEUSILIN - S1, FH2, US2 (granular/powder, and UFL2 - Fuji Chemical Industries (USA) Inc., Robbinsville, N.J.).
The anti-flatulents used in the compositions are selected from dimethicone, simethicone and other organopolysiloxane antifoam agent or combinations thereof. The amount of simethicone or other organopolysiloxane antifoam agent contained in the solid oral dosage form should be sufficient to provide a therapeutic dosage to a patient suffering from gas or flatulence and associated symptoms. The preferred dosage range for simethicone is in the range of about 10 mg to about 50 mg per dosage unit. The dose range may vary according to the age and weight of the patient as well as the severity of symptoms.
The ratio of simethicone to the adsorbent such as magnesium aluminometasilicate is selected in such a way that relatively high amount of simethicone is adsorbed on the adsorbent to provide smaller size tablets for equivalent amount of active ingredients, as compared to the composition, wherein the ratio of simethicone to adsorbent is less. The said ratio (Simethicone: Adsorbent) is selected to be atleast 1:1.75 or more preferably in the range of 1: 0.5 to 1:1.5. As we reduce the ratio of the simethicone to adsorbent for example say 1:2, higher amount of adsorbent is used to adsorb given quantity of simethicone. It is understood from the above explanation that the lesser or higher values of the ratio of simethicone to adsorbent are construed in terms of the value of the quotient obtained from the said ratio. It means that according to the present invention the quotient of the amount of simethicone to the amount of silicate adsorbent is atleast about 0.5714 and is more preferably in the range of 0.6667 to 0.2.
In the formulations of present invention the anti-flatulent like simethicone is adsorbed on magnesium aluminometasilicate, to provide compositions comprising simethicone with one or more antacids such as Magaldrate, which have excellent flow properties, wherein the ratio of simethicone to magnesium aluminometasilicate is at least 1:1.75. Such composition could be compressed in to tablets, which would

disperse rapidly with minimum chewing in the mouth as well as disintegrate rapidly in the stomach, when swallowed without chewing, resulting in prompt therapeutic action of antacids, anti-flatulent in the treatment of hyperacidity and flatulence through out the shelf life of the formulation.
In the present disclosure, the amount and the type of antacids used may be selected in accordance with the acid neutralizing capacity desired to be achieved with a single does of the antacid. For example, the formulation with 250 mg of Magnesium hydroxide and 200 mg of Aluminum hydroxide as disclosed in the example 4 of the patent EP 0,003,589 shows the acid neutralizing capacity of 5.85 mEq for a total weight of about 774 mg and another composition (Gelusil MPL, Pfizer India) comprising 250 mg of Magnesium Hydroxide, 250 mg of Dried Aluminium Hydroxide gel with 50 mg Magnesium Aluminum silicate provide acid neutralizing capacity of about 6 mEq with the total weight of the formulation of about 1154mg .
More over, a formulation comprising 400 mg Magaldrate and 20mg simethicone (Ulgel, Alembic) showed acid neutralization capacity of 8.5 with a total weight of the formulation of about 1195 mg. On the other hand, the composition disclosed in the present invention comprising 400 mg of Magaldrate with total weight not more than about 700 mg provides acid neutralizing capacity of about 8.5 mEq whereas the composition with 800 mg of Magaldrate having the total weight not more than about 1360 mg provides the acid neutralizing capacity of about 17 mEq once measured as per the standards of Indian Pharmacopoeia.
Further, the in vitro efficacy of a formulation of present invention and the marketed formulation (Ulgel, Alembic Pharmaceuticals Ltd.) having the dose of 400 mg Magaldrate and 20 mg Simethicone was compared using the Rossett & Rice method known in the art. (N. E. Rossett and Marion L. Rice, JR, Antacids, March 195, Vol. 26, No. 3,Pages 490-5) The results provided in the Figure 1 clearly indicate that the formulation of the present invention provide superior efficacy in terms of neutralizing the acid. The formulation of present invention neutralizes the acid more efficiently and rapidly as compared to the reference product (Ulgel, Alembic Pharmaceuticals Ltd.). The results also indicate that due to rapid disintegration of the formulation into very fine suspension, relatively higher surface area is available for acid neutralization which translates in to improved efficacy of the formulation.
The antacids such as Magaldrate include the antacids with similar acid neutralizing capacity when used in the equivalent quantum as well as the antacids that in combination with antiflatulents such as simethicone can be compressed in the form of oral formulations with a disintegration time less than about 10 minutes. The said disintegration time of the formulations of present invention is preferably less than about 5 minutes and more preferably less than about 3 minutes. Further, the composition of the

present invention ensure that the disintegration time of the said composition comprising antacids in combination with antiflatulents such as simethicone, do not increase beyond the acceptable limit for a tablet to be swallowed upon storage. Accordingly, the disintegration times of the compressed formulations of antacids such as Magaldrate in combination with antiflatulents such as simethicone as per the present invention are maintained within the acceptable limits throughout the shelf life of the formulation.
The ratio of the amount of antacids such as Magaldrate to the amount of other ingredients of the formulation including the antiflatulent such as simethicone can be selected according to the dose of the antacid that needs to be incorporated in the formulation after considering the desired acid neutralizing capacity of the formulation.
The formulation of the present invention can be prepared for the dose of about 450 mg of antacids such as Magaldrate in order to achieve the acid neutralizing capacity of not less than 7 mEq. It was surprisingly found that when such formulations of antacids in combination with antiflatulents were prepared in accordance with the present invention, the acid neutralizing capacity of more than 7 mEq was achieved without increasing the weight of the table beyond 700 mg. Therefore the formulations of the present invention provide an additional advantage of higher acid neutralizing capacity at the same time providing an option of directly swallowing the formulation without any difficulty due to larger size or thickness of the formulation. Accordingly, for the formulation of present invention with weight not more than about 700 mg, the diameter of the formulation is not more than about 16/32 inch and the thickness of the formulations is not more than about 5 mm.
Such formulations comprising antacids such as Magaldrate in combination with antiflatulents such as Simethicone according to the present invention provide the acid neutralizing capacity of not less than 7 mEq without impairing the antiflatulent action of Simethicone. In order to achieve this benefit the quantum of antacid such as Magaldrate is selected in such a way that the ratio of the amount of antacid to the amount of other ingredients of the formulation including simethicone is atleast about 1: 0.7 preferably the said ratio is atleast about 1:0.69 and more preferably the said ratio is atleast about 1:0.6833. As the ratio of antacid to the other ingredients reduces from the said ratio for example say 1:0.75 or 1:0.8 etc. the amount of antacid included in the formulation reduces for a given weight of the formulation. It is cognizable that the higher or lesser values of the said ratio needs to be interpreted in terms of the value of the quotient obtained by dividing the amount of antacid with the amount of other ingredients of the formulation including the antiflatulent. Accordingly the said quotient of the obtained by dividing the amount of antacid with the amount of other ingredients of the formulation including the antiflatulent is atleast about 1.4286.

The formulation of the present invention can also be prepared for the dose of around 800 mg of antacids such as Magaldrate in order to achieve the acid neutralizing capacity of not less than 15 mEq. It was surprisingly found that when such formulations of antacids in combination with antiflatulents were prepared in accordance with the present invention, the acid neutralizing capacity of more than 15 mEq was achieved without increasing the weight of the table beyond about 1360 mg. Such formulation of higher dose of the antacids can be prepared in the form of compressed oval shaped tablets that can be swallowed easily. Therefore the formulations of the present invention provide an additional advantage of higher acid neutralizing capacity at the same time providing an option of directly swallowing the formulation without any difficulty due to larger size or thickness of the formulation. Accordingly, the dimensions of the formulation with higher dose of the antacids such as Magaldrate are selected in such a way that the formulation is easily swallowable for example in the form of an oval or capsule shaped tablet. According to the formulations of the present invention with weight not more than about 1360mg, the length of the formulation is not more than about 23 mm, the width of the formulation is not more than about 10 mm and the thickness of the formulation is not more than about 7 mm.
Such formulations comprising antacids such as Magaldrate in combination with antiflatulents such as Simethicone according to the present invention provide the acid neutralizing capacity of not less than 15 mEq without impairing the antiflatulent action of Simethicone. In order to achieve this benefit the quantum of antacid such as Magaldrate is selected in such a way that the ratio of the amount of antacid to the amount of other ingredients of the formulation including simethicone is atleast about 1: 0.70. As the ratio of antacid to the other ingredients reduces from the said ratio for example say 1:0.75 or 1:0.8 etc. the amount of antacid included in the formulation reduces for a given weight of the formulation. As stated above, the higher or lesser values of the said ratio can to be interpreted in terms of the value of the quotient obtained by dividing the amount of antacid with the amount of other ingredients of the formulation including the antiflatulent. Accordingly, the said quotient of the obtained by dividing the amount of antacid with the amount of other ingredients of the formulation including the antiflatulent is atleast about 1.4286.
According to the present invention, irrespective of the dose of the antacids included in the formulation of the present invention the ratio of the amount of antacid to the amount of other ingredients of the formulation including the antiflatulent is atleast about 1: 0.70. As we reduce the ratio of antacid to the other ingredients of the formulations including antiflatulent such as simethicone from 1:0.70 for example to 1:0.75, or to 1:1.7, or to 1:1.72 etc. the amount of antacid included in the formulation reduces and the amount of other ingredients of the formulations increases for a given weight of the

formulation. It is understood from the above explanation that the lesser or higher values of the ratio of the amount of antacid to the amount of other ingredients of the formulation are construed in terms of the value of the quotient obtained from the said ratio. Therefore according to the present invention the value of the said quotient is atleast about 1.4286.
The formulations of the present invention further comprise pharmaceutically acceptable disintegrating agents suitable for compressed oral formulations. The said disintegrating agents can be selected from a group of Starch (corn or maize), pregelatinized starch e.g. Starch 1500 G, clays (Veegum or Bentonite), microcrystalline cellulose, cellulose and powdered cellulose or derivatives thereof; or Super-disintegrating agents selected from sodium starch glycolate, sodium salt of carboxymethyl starch, modified cellulose and cross- linked polyvinyl pyrrolidone. Sodium starch glycolate is available commercially under the trade names Explotab® (Edward Mendell Co.), Primojel® (Generichem Corp) and Tablo® (Blanver, Brazil). An example of modified cellulose includes croscarmellose, sodium salt of carboxymethyl cellulose etc. Croscarmellose is available commercially under the trade names AcDiSol® (FMC Corf).), Nymcel ZSX® (Nyma, Netherlands), Primellose® (Avebe, Netherlands), Solutab® (Blanver, Brazil). An example of a cross-linked polyvinyl pyrrolidone includes Crospovidone and the like.
More preferably, in the formulations of present invention the pharmaceutically acceptable disintegrating agents are super-disintegrating agents. The said disintegrating agents are used in an amount necessary to achieve the disintegration time of the formulation that is less than about 10 minutes at the room temperature. The said disintegration time of the formulations of present invention is preferably less than about 5 minutes and more preferably less than about 3 minutes.
It is obvious from the disclosures and the teachings of the prior art that in order to achieve rapid disintegration of formulations of antacids in combination with antiflatulents, the quantum of the excipients augmenting the disintegration time of the formulations including the disintegrating agents should be increased. In effect, for a given weight of the formulation, the amount of antacid component incorporated is reduced as compared to the amount of the other ingredients of the formulations, resulting in lower acid neutralization capacity. Moreover, mere achievement of the rapid disintegration time of such formulations is not sufficient as it does not address the formulation issue related to increase in the disintegration time upon storage arising from the nature of the combination of antacids such as Magaldrate and antiflatulents such as Simethicone.
Therefore, it is difficult to obtain formulations comprising antacids in combination with antiflatulents

that provide rapid disintegration maintained within the acceptable limit for the swallowable tablets throughout the shelf life and yet achieve high acid neutralization capacity for the size of the formulations that can be either sucked/chewed mildly or swallowed directly without chewing.
It was surprisingly found that the formulations of present invention provide high acid neutralization capacity for given weight of the formulations and yet achieve rapid disintegration time well within the acceptable limit all throughout the shelf life. At the same time, the size and the weight of formulations for a desired dose of antacids to be incorporated in the formulations is not increased significantly resulting in the formulations that can either be sucked/chewed mildly or swallowed directly without chewing.
More surprisingly, according to the formulations of the present invention, a careful selection of the ratio of the antacid to the other ingredients of the formulation including antiflatulent and the type and the amount of the disintegrating agent not only resulted in excellent acid neutralizing capacity but also the formulations provided rapid disintegration throughout the shelf life. It is important to note that while achieving these advantages the weight and therefore the size of the compressed formulation is maintained in such a way that the formulation so formed can be easily swallowed directly without chewing if desired.
The amount and type of disintegrating agent is selected in order to achieve rapid disintegration of the formulation if the formulation is sucked/chewed mildly or swallowed directly without chewing. More preferably the amount of disintegrating agent used in the formulation is less than about 7%, preferably less than about 5% by weight of the formulation.
The formulations of present invention may also comprise one or more pharmaceutically acceptable excipients selected from a group comprising Binders, Diluents, Lubricants. Glidants, Preservatives, Sweetening agents, and Flavoring agents.
The said diluents may be selected from a group comprising sucrose, glucose, lactose, fructose, dextrose, poly dextrose, maltose, dextrin, starch, pre-gelatinized starch, mannitol, lacititol, sorbitol, xylitol, malto dextrin, maltitol, lacititol, iso-malt, erythritol, directly compressible lactose, directly compressible mannitol, directly compressible starch, microcrystalline cellulose and such other conventionally used diluents.
The said binders may be selected from a group comprising microcrystalline cellulose, starch, corn

maize starch, modified corn starch, wheat starch, modified wheat starch, potato starch, pregelatinized starch such as commercially available Starch 1500 G or prejel; polymers and cellulose derivatives or combinations thereof. If the binding agent includes a polymer, suitably it is polyvinyl pyrrolidone or povidone (PVP), polyvinyl alcohol (PVA), polyethylene oxide, polaxamer, polymethacrylate e.g. a carbomer, polyethylene glycol (PEG) such as PEG 3350 and calcium polycarbophil; or a combination of two or more thereof. If the binding agent includes a cellulosic derivative it is preferably hydroxypropyl cellulose (HPC) (low to medium viscosity versions thereof) such as commercially available Klucel®, (Aqualon division of Hercules Inc.) or Klucel GF, Klucel JF, Klucel LF and Klucel EF; hydroxypropylmethyl cellulose (HPMC) (low to medium viscosity versions thereof) e.g. commercially available Methocel CR, Methocel El5 Premium, Methocel E3 Premium LV, Methocel KIOOLV (Dow Chemical Company) etc., carboxymethylcellulose (CMC), sodium carboxymethylethyl cellulose; or a combination thereof.
The said lubricants may be selected from a group comprising calcium stearate, hydrogenated castor oil, glycerine monostearate, magnesium lauryl sulphate, magnesium stearate, myristic acid, sodium stearyl fumarate, fumaric acid, stearic acid, maleic acid, talc, zinc stearate, colloidal silica dioxide and the like or combination thereof.
The formulation of present invention may comprise pharmaceutically acceptable glidants selected from talc, silicone dioxide, hydro phobic colloidal silica, tribasic calcium phosphate and the. like or combination thereof.
The sweetening agents if used in the formulation of present invention may be selected from a group comprising sugar, fructose, glucose, dextrose, Maltose, Aspartame, saccharine, sucralose, stevia, stevio-sides and the likes or combination thereof. The formulation of the present invention may further comprise one or more pharmaceutically acceptable flavoring agents or coloring agents or combination thereof in order to obtain desired flavors and improve the organoleptic properties of the formulations.
The formulations of the present invention may further comprise pharmaceutically acceptable excipients to improve the stability or prevent microbial growth in the formulations such as anti-oxidants/ chelating agent or preservatives. The said Preservatives may be selected from a group comprising methyl paraben, ethyl paraben, propyl paraben, benzalkonium chloride, benzoic acid, benzyl alcohol, bronopol, butylated, hydroxyl anisole, butylated hydroxyl toluene, chlorocresol, Isopropyl alcohol,
Another embodiment, the present invention is to provide novel pharmaceutical composition comprising one or more antacid and at least one anti-flatulent in the form of a free flowing compressible mass,

which can be further compressed to provide a tablet, which provides rapid therapeutic actions both when sucked/chewed mildly and swallowed without chewing, processes for preparing the same and methods of use of such composition.
Another embodiment of the present invention is to provide compressed oral formulations of one or more antacids such as Magaldrate and antiflatulents such as simethicone in order to achieve rapid disintegration of the formulations not only in the oral cavity if the formulations are sucked or chewed mildly but also in the stomach when the formulations are swallowed without chewing. This feature of the formulations results in the advantage of providing rapid onset of therapeutic action in the treatment of hyperacidity and flatulence.
The type and the amount of said pharmaceutically acceptable excipients used in the formulations of present invention are selected in such a way that the ratio of the amount of antacid to the amount of other ingredients of the formulation including Simethicone is atleast 1:0.70. Further, the formulations of present invention are designed in such a way that the disintegration time for the formulations in the environment of the oral cavity or in the stomach is less than about 10 minutes. The said disintegration time of the formulations of present invention is preferably less than about 5 minutes and more preferably less than about 3 minutes.
Another embodiment of the present invention is to provide compressed oral formulation of one or more antacids such as Magaldrate and antiflatulents such as simethicone in order to achieve characteristics of the formulation such as hardness, and disintegration time of the compressed formulations that are maintained within the acceptable limit throughout the shelf life. These formulations avoid the disadvantage of hardening of the compressed formulation upon storage leading to impaired therapeutic effectiveness.
The compressed formulations of present invention may be prepared by the process known in the art including direct compression or wet granulation methods for the preparation of tablets. The hardness of the compressed formulation according to the present invention is adjusted in such a way that rapid disintegration of the formulation, in less than about 10 minutes, preferably less than about 5 minutes and more preferably less than about 3 minutes, is achieved not only in the oral cavity if the formulation is sucked or chewed mildly but also in the stomach when the formulation is swallowed without chewing. Further the hardness of the tablet is optimized for the disintegration time as well as the friability of the formulations. The hardness of the prefered formulations is not more than 18 Kgf.

In another embodiment, the present invention provides a method for making free flowing composition of antacids and anti-flatulent that can be compressed into oral unit dosage forms. The method includes (i) blending an anti-flatulent such as simethicone with an adsorbent such as magnesium aluminometasilicate to ensure that the entire amount of the anti-flatulent is adsorbed on the said adsorbent; (ii) blending the mixture of step (i) with antacids, along with one or more pharmaceutically acceptable excipients such as disintegrates agents, flavors, lubricants, sweeteners and diluents to produce a free flowing composition.
In another embodiment the mixture of step (i) stated above can be blended with the granules of antacids such as Magaldrate along with one or more pharmaceutically acceptable excipients such as disintegrates agents, flavors, lubricants, sweeteners and diluents that are prepared from the wet granulation process known in the art.
The formulations compressed from such compositions have excellent hardness resulting in low friability of the formulations the and yet disintegrate rapidly. When chewed in the mouth they disperse rapidly, within about 10 minutes and preferably within about 5 minutes and more preferably within about 3 minutes, to fine particles, to form a pleasant tasting fine suspension, without any large agglomerates.
EXAMPLES
The following non-limiting examples illustrate in details about the invention. However, they are, not intended to be limiting the scope of present invention in any way.

EXAMPLE 1
No Ingredients mg/Tab
01 Magaldrate 483
02 Mannitol 100
03 Crospovidone 6
04 Starch (1.78%) 12.25
05 Methyl paraben 0.125
06 Propyl Paraben 0.125
07 Water q.s.
08 Simethicone 20
09 Magnesium aluminometasilicate (Neuciline US2, granular form) 30

10 Perlitol 16
11 Crospovidone 6
12 Sucralose 4.5
13 Aneeseed Flavour 4
14 Talc 3
15 Magnesium stearate 3
Average weight 688 mg
Manufacturing procedure:
1. Blend Magaldrate with Mannitol and Crospovidone.
2. Prepare a Starch Paste incorporating Methyl Paraben and Propyl Paraben.
3. Bind the blend of step (1) with starch paste of step (2) to form a mass.
4. Granulate the mass of step (3) and dried the granules .
5. Blend Magnesium Aluminometasilicate (Neuciline US2, granular form) with Simethicone to ensure
that entire quantity of Simethicone is adsorbed by Magnesium Aluminometasilicate.
6. Blend the granules of step (4) with the blend of Simethicone and Magnesium Aluminometasilicate
(Neuciline US2, granular form), as obtained in step (5).
7. Add Perlitol, Crospovidone, Sucralose, Aneeseed flavor, Talc and Magnesium stearate to the blend,
as obtained in step (6).
8. Compress the blend of step (7) using 16/32 inch diameter puches, to produce tablets with hardness of
value about 10-14 Kgf and having disintegration time of about 2 minutes. The tablets disperse to
fine particles in about 2 minutes, when sucked or chewed mildly. The acid neutralizing capacity of
the tablet is more than 7mEq.
EXAMP LE2
No Ingredients mg/Tab
01 Magaldrate 800
02 Simethicone 50
03 Magnesium aluminometasilicate (Neuciline US2, granular form) 75
04 Flowlac 100 175
05 Perlitol 150
06 Crospovidone 20
07 Sucralose 10
08 Aneeseed Flavour 8
09 Talc 6
10 Magnesium stearate 6

Average Weight 1300
Manufacturing procedure:
1. Blend Simethicone with Magnesium Aluminometasilicate (Neuciline US2, granular form) to ensure
that entire quantity of Simethicone is adsorbed by Magnesium Aluminometasilicate.
2. Add Magaldrate to the blend of step (1) and blend the mixture.
3. Add Flowlac 100, Perlitol, Crospovidone, Sucralose, Aneeseed flavor, Talc and Magnesium stearate
to the blend of step (2).
4. Compress blend of step (3) using 16/32 inch diameter puches, to produce tablets with hardness of
value about 14 to 18 Kgf and having disintegration time is about 3 minutes. The tablets disperse to fine
particles in about 2 minutes, when sucked or chewed mildly. The acid neutralizing capacity of the tablet
is more than 16 mEq.
EXAMPLE 3
No. Ingredients Mg/Tab
01 Magaldrate 483
02 Mannitol 100
03 Crospovidone 6
04 Starch (1.78%) 12.25
05 Methyl paraben 0.125
06 Propyl Paraben 0.125
07 Water q.s.
08 Simethicone 20
09 Magnesium aluminometasilicate (Neuciline US2, granular form) 20
10 Perlitol 16
11 Crospovidone 6
12 Sucralose 4.5
13 Aneeseed Flavour 4
14 Talc 3
15 Magnesium stearate 3
Manufa Average weight 678 mg.

cturine procedure:
1. Blend Magaldrate with Mannitol and Crospovidone.
2. Prepare a Starch Paste incorporating Methyl Paraben and Propyl Paraben.
3. Bind the blend of step (1) with starch paste of step (2) to form amass.
4. Granulate the mass of step (3) and dried the granules.
5. Blend Magn esium Aluminometasilicate (Neuciline US2, granular form) with S imethicone tc ) ensure

that an entire quantity of Simethicone is adsorbed by Magnesium Aluminometasilicate.
6. Blend the granules of step (4) with the blend of Simethicone and Magnesium Aluminometasilicate
(Neuciline US2, granular form), as obtained in step (5).
7. Add Perlitol, Crospovidone, Sucralose, Aneeseed flavor, Talc and Magnesium stearate to the blend,
as obtained in step (6).
8. Compress the blend of step (7) using 16/32 inch diameter puches, to produce tablets with hardness of
value about 10 to 14 kgf & disintegration time is about 2 minutes. The tablets disperse to fine particles
in about 2 minutes, when sucked or chewed mildly. The acid neutralizing capacity of the tablet is more
than 7mEq.
EXAMPLE 4
No Ingredients mg/Tab
01 Magaldrate 483
02 Mannitol 104
03 Crospovidone 6
04 Starch (1.78%) 12.25
05 Methyl paraben 0.125
06 Propyl Paraben 0.125
07 Water q.s.
08 Simethicone 20
09 Magnesium aluminometasilicate (Neuciline US2, granular form) 15
10 Perlitol 16
11 Crospovidone 6
12 Sucralose 4.5
13 Aneeseed Flavour 4
14 Talc 3
15 Magnesium stearate 3
Average weight 678 mg
Manufa cturing procedure:
1. Blend Magaldrate with Mannitol and Crospovidone.
2. Prepare a Starch Paste incorporating Methyl Paraben and Propyl Paraben.
3. Bind the blend of step (1) with starch paste of step (2) to form a mass.
4. Granulate the mass of step (3) and dried the granules .
5. Blend Magnesium Aluminometasilicate (Neuciline US2, granular form) with Simethicone to ensure
that entire quantity of Simethicone is adsorbed by Magnesium Aluminometasilicat e.

6. Blend the granules of step (4) with the blend of Simethicone and Magnesium Aluminometasilicate
(Neuciline US2, granular form), as obtained in step (5).
7. Add Perlitol, Crospovidone, Sucralose, Aneeseed flavor, Talc and Magnesium stearate to the blend,
as obtained in step (6).
8. Compress the blend of step (7) using 3 6/32 inch diameter puches, to produce tablets with hardness of
value about 10 to 14 Kgf & disintegration time is about 2 minutes. The tablets disperse to fine particles
in about 2 minutes, when sucked or chewed mildly. The acid neutralizing capacity of the tablet is more
than 7mEq.
EXAMPLE 5
No. Ingredients Mg/Tab
01 Magaldrate 483
02 Mannitol 100
03 Crospovidone 6
04 Starch (1.78%) 12.25
05 Methyl paraben 0.125
06 Propyl Paraben 0.125
07 Water q.s.
08 Simethicone 20
09 Synthetic Amorphous Silica (Zeopharm 80) 30
10 Perlitol 16
11 Crospovidone 6
12 Sucralose 4.5
13 Aneeseed Flavour 4
14 Talc 3
15 Magnesium stearate 3
Average weight 688 mg.
Manufacturing P rocedure:
1. Blend Magaldrate with Mannitol and Crospovidone.
2. Prepare a Starch Paste incorporating Methyl Paraben and Propyl Paraben.
3. Bind the blend of step (1) with starch paste of step (2) to form a mass.
4. Granulate the mass of step (3) and dried the granules .
5. Blend Synthetic Amorphous Silica (Zeopharm 80) with Simethicone to ensure that entire quantity of
Simethicone is adsorbed by Synthetic Amorphous Silica (Zeopharm 80)
6. Blend the gr anules of step (4) with the blend of Simethicone and Synth etic Amorphous

Silica(Zeoph arm 80), as obtained in step (5).
7. Add Perlitol, Crospovidone, Sucralose, Aneeseed flavor, Talc and Magnesium stearate to the blend,
as obtained in step (6).
8. Compress the blend of step (7) using 16/32 inch diameter puches, to produce tablets with hardness of
value about 6-8 Kgf & disintegration time is about 2 minutes. The tablets disperse to fine particles in
about 2 minutes, when sucked or chewed mildly. The acid neutralizing capacity of the tablet is more
than 7mEq.
EXAMPLE 6
No. Ingredients Mg/Tab
01 Magaldrate 483
02 Mannitol 100
03 Crospovidone 6
04 Starch (1.78%) 12.25
05 Methyl paraben 0.125
06 Propyl Paraben 0.125
07 Water q.s.
08 Simethicone 20
09 Synthetic Amorphous Silica (Zeopharm 80) 35
10 Perlitol 16
11 Crospovidone 6
12 Sucralose 4.5
13 Aneeseed Flavour 4
14 Talc 3
15 Magnesium stearate 3
Average weight 693 mg
Manufacturing i procedure:
1. Blend Magaldrate with Mannitol and Crospovidone.
2. Prepare a Starch Paste incorporating Methyl Paraben and Propyl Paraben.
3. Bind the blend of step (1) with starch paste of step (2) to form a mass.
4. Granulate the mass of step (3) and dried the granules .
5. Blend Synthetic Amorphous Silica(Zeopharm 80) with Simethicone to ensure that entire quantity of
Simethicone is adsorbed by Synthetic Amorphous Silica(Zeopharm 80)
6. Blend the granules of step (4) with the blend of Simethicone and Synthetic Amorphous
Silica(Zeopha rm 80), as obtained in step (5).

7. Add Perlitol, Crospovidone, Sucralose, Aneeseed flavor, Talc and Magnesium stearate to the blend,
as obtained in step (6).
8. Compress the blend of step (7) using 16/32 inch diameter puches, to produce tablets with hardness of
value about 6-8 Kgf & disintegration time is about 2 minutes. The tablets disperse to fine particles in
about 2 minutes, when sucked or chewed mildly. The acid neutralizing capacity of the tablet is more
than 7mEq.
EXAMPLE 7
Sr.no
Ingredients Quantity
(mg/tab)
1 Magaldrate 400
2 Mannitol** 158.5
Crospovidone 15
4 Colour Ponceau4R Supra 0.172
5 Colour Erythrosine 0.172
6 Starch 12.25
7 Methyl paraben 0.125
8 Propyl Paraben 0.125
9 Simethicone 20
10 Magnesium aluminometasilicate (Neuciline US2, granular form) 20
11 Mannitol spray dried (Pearlitol) 16
12 Crospovidone 15
13 Sucralose 6
14 Aniseed Flavour TP-130 powder 4
15 Talc 3
16 Magnesium stearate 3
Avg. wt 673.34
Manuf acturing procedure:
1. Blend Magaldrate with Mannitol and Crospovidone.
2. Prepare a Starch Paste incorporating Methyl Paraben and Propyl Paraben.
3. Bind the blend of step (1) with starch paste of step (2) to form a mass.
4. Granulate the mass of step (3) and dried the granules .
5. Blend Magne sium Aluminometasilicate (Neuciline US2, granular form) with Simet hi cone to en sure

that entire quantity of Simethicone is adsorbed by Magnesium Aluminometasilicate.
6. Blend the granules of step (4) with the blend of Simethicone and Magnesium Aluminometasilicate
(Neuciline US2, granular form), as obtained in step (5).
7. Add PerJitol, Crospovidone, Sucralose, Aneeseed flavor, Talc and Magnesium stearate to the blend.
as obtained in step (6).
8. Compress the blend of step (7), to produce tablets with hardness of value about 4-5 Kgf &
disintegration time is about 1 minute. The tablets disperse to fine particles in about 2 minutes, when
sucked or chewed mildly. The acid neutralizing capacity of the tablet is more than 7mEq. The tables
with the formula stated above were compressed in the form of a petal shaped tablets or round tablets by
using a 16/32 inch diameter puches.
EXAMPLE 8
Sr.
No Ingredients Quantity (mg/tab)
1 Magaldrate 800
2 Mannitol 333.02
3 Crospovidone 30
4 Colour Ponceau4R Supra 0.334
5 Colour Erythrosine 0.334
6 Starch 24.50
7 Methyl paraben 0.250
8 Propyl Paraben 0.250
9 Simethicone 40
10 Magnesium aluminometasilicate (Neuciline US2, granular form) 40
11 Mannitol spray dried (Pearlitol) 32.312
12 Crospovidone 30
13 Sucralose 9
14 Aniseed Flavour TP-130 powder 8
15 Talc 6
16 Magnesium stearate 6
Avg. wt 1360

Manufacturing procedure:
1. Blend Magaldrate with Mannitol and Crospovidone.
2. Prepare a Starch Paste incorporating Methyl Paraben and Propyl Paraben.
3. Bind the blend of step (1) with starch paste of step (2) to form a mass.
4. Granulate the mass of step (3) and dried the granules .
5. Blend Magnesium Aluminometasilicate (Neuciline US2, granular form) with Simethicone to ensure
that entire quantity of Simethicone is adsorbed by Magnesium Aluminometasilicate.
6. Blend the granules of step (4) with the blend of Simethicone and Magnesium Aluminometasilicate
(Neuciline US2, granular form), as obtained in step (5).
7. Add Perlitol, Crospovidone, and Sucralose, Aneeseed flavor, Talc and Magnesium stearate to the
blend, as obtained in step (6).
8. Compress the blend of step (7), to produce tablets with hardness of value about 4-5 Kgf &
disintegration time is about 1 minute. The tablets disperse to fine particles in about 2 minutes, when
sucked or chewed mildly. The acid neutralizing capacity of the tablet is more than 16 mEq. The tables
with the formula stated above were compressed in the form of an oval or capsule shaped tablets with
length of not less than about 22.6mm, width of not less than about 10mm and the thickness of about 7
mm.
In the above description, like reference characters designate like or corresponding parts throughout the several illustrations shown in figures/examples. It is also understood that terms such as "a", "an", "the", and like are words for convenience and are not to be constructed as limiting terms. Moreover, it will be understood that the illustrations are for the purpose describing exemplary embodiment of the invention thereto.

We claim:
1. A compressed oral formulation of antacid and antiflatulent comprising therapeutically effective amount of antacids such as Magaldrate in combination with antiflatulent agents such as Simethicone adsorbed on a silicate adsorbent and a disintegrating agent, wherein the ratio of the amount of antacid to the amount of other ingredients including antiflatulent agent such as Simethicone is atleast about 1:0.70 and the disintegration time of the formulation is less than about 10 minutes if the formulation is sucked or swallowed directly without chewing,
2. A compressed oral formulation as claimed in claim 1, wherein the disintegration time of the formulation is preferably less than about 5 minutes.
3. A compressed oral formulation as claimed in claim 1, wherein the disintegration time of the formulation is more preferably less than about 3 minutes.
4. A compressed oral formulation as claimed in claim 1, wherein the disintegration time of the formulation for complete shelf life is maintained within the acceptable standard limit for tablets to be swallowed.
5. A compressed oral formulation as claimed in any one of the preceding claims, wherein the amount of the disintegrating agent used in the formulation is less than about 7% by weight of the formulation.
6. A compressed oral formulation as claimed in any one of the preceding claims, wherein the amount of the disintegrating agent used in the formulation is preferably less than about 5% by weight of the formulation.
7. A compressed oral formulation as claimed in any one of the preceding claims, wherein the hardness of the formulation is not more than about 18 kgf.
8. A compressed oral formulation as claimed in any one of the preceding claims, wherein the ratio of the amount of antiflatulent agent such as Simethicone to the amount of the silicate adsorbent is atleast about 3:1.75.
9. A compressed oral formulation as claimed in claim 8, wherein the ratio of the amount of antiflatulent agent such as Simethicone to the amount of the silicate adsorbent is preferably in the range of about 1: 0.5 to 1:1.5.
10. A compressed oral formulation as claimed in claim 1, wherein the acid neutralizing capacity of the formulation is not less than about 7 mEq.
11. A compressed oral formulation as claimed in claim 10 wherein the weight of the formulation is not more than about 700 mg, the thickness of the formulation is not more than about 5 mm and the diameter of the formulation is not more than about 16/32 inches.
12. A compressed oral formulation as claimed in claim 10, wherein the acid neutralizing capacity of the

formulation is not less than about 15 mEq.
13. A compressed oral formulation as claimed in claiml2, wherein the weight of the formulation is not more than about 1360 mg, the thickness of the tablet is not more than about 7 mm, the length of the formulation is not more than about 23 mm and the width of the formulation is not more than about 10 mm.