DESC:TECHNICAL FIELD OF THE INVENTION

The invention relates to a chewable tablet composition comprising sulpho-adenosyl-L-methionine (SAMe) or a salt thereof. In particular, the invention relates to chewable tablet comprising sulpho-adenosyl-L-methionine or salt thereof, an alkalizing agent, a moisture repelling agent and one or more pharmaceutically acceptable excipients. The invention is particularly designed for systemic buccal delivery. The invention further provides the process for preparing the tablet composition.

BACKGROUND OF THE INVENTION

Administration of drugs through oral route is the most common and the easiest way to administer a drug. However, pediatric, geriatric and bedridden patient shows inconvenience for swallowing conventional tablets or capsules due to difficulties in swallowing with lesser amounts of water with the medication, unable to tolerate the taste of many drugs when formulated as liquid dosage forms, resulting in poor patient compliance.

Chewable tablets are solid, single dose preparations intended for chewing to obtain a local or systemic effect. These are formulated and manufactured so that they may be chewed in the mouth producing a pleasant tasting residue in the oral cavity that is easily swallowed and does not leave a bitter or unpleasant taste.

S-adenosylmethionine (SAMe) is a natural molecule synthesized from the amino acid methionine in the presence of magnesium and adenosine triphosphate (ATP). The SAMe molecule is a carrier of methyl groups and provides a sulfur molecule as well. The liver is a site of methylation and sulfation reactions necessary for detoxification, and can use SAMe to assist in these processes. SAMe is also a cofactor in several metabolic reactions. By donating its methyl group, SAMe is converted to adenosylhomocysteine which, in turn, is rapidly hydrolysed to adenosine and homocysteine and eventually to the amino acid, cysteine.

S-adenosylmethionine is necessary for the production of glutathione, the primary antioxidant found in the liver. SAMe has also been found effective in the treatment of cholestasis. SAMe is also used in the treatment of fibromyalgia, osteoarthritis and depression.

SAMe is a highly temperature sensitive and moisture sensitive material. Therefore, several researches have attempted to provide stable salts of SAMe which can be used in drug formulations (e.g. US Patent 5,114,931 and 4,309,177).

The US Patent Number 3,893,999 and 4,057,686 discloses different salts of SAMe such as 1-4 butane sulphonates and disulphate tosylates. These salts can be prepared by conventional methods such as fermentation or the synthetic route.

Most SAMe salts are hygroscopic and quickly degrade on exposure to moisture and heat. Pharmacokinetic studies conducted in respect of SAMe suggest that the drug is mainly absorbed in the intestinal tract, specifically, the duodenum. Currently, SAMe is available in the market mostly in the tablet form.

The absorption time of this drug in solid dosage form is relatively long and erratic for at least two reasons: first, the drug is introduced into the body as a solid and therefore must be dissolved before it can be absorbed by the body; secondly, the acidic environment of the stomach influences absorption of SAMe. Moreover the active ingredient does not get absorbed in the intestine as intended or desired by the manufacturer.

US Patent No. 7,838,030 describes stable pharmaceutical composition of SAMe or salt thereof.

US Patent Publication No 20110236463 discloses pharmaceutical composition for systemic buccal delivery, in particular chewing gums, chewable tablets, orodispersible tablets and oromucosal preparations comprising SAMe.

Accordingly, there is a need for preparing chewable composition comprising SAMe that exhibits reduced hygroscopicity and increased stability.

The inventors of the inventions have surprisingly found that by the addition of alkalizing agent, it is possible to achieve an improved composition of SAMe or a salt thereof that in turn show increased stability.

The inventors of the inventions further unexpectedly found that, moisture repelling agent such as magnesium aluminometasilicate, when used in a different manner to prepare chewable dosage forms, that overcomes or at least ameliorates the problems associated with SAMe or salt thereof.

SUMMARY OF THE INVENTION

In one general aspect, there is provided a chewable tablet composition comprising SAMe or a salt thereof in combination with alkalizing agent and one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a chewable tablet composition comprising SAMe or a salt thereof in combination with moisture repelling agent and one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a chewable dosage form comprising of SAMe or a salt thereof, an alkalizing agent, a moisture repelling agent and one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a chewable tablet comprising SAMe or a salt thereof in an amount of between 5% to 95% by weight in combination with an alkalizing agent and one or more pharmaceutical acceptable excipients.

In another general aspect, there is provided a chewable tablet comprising SAMe or a salt thereof in an amount of between 5% to 95% by weight, in combination with an alkalizing agent in an amount of between 0.01% to 30% by weight, preferably between 0.5% to 15% by weight, relative to the weight of the composition.

In another general aspect, there is provided a chewable tablet comprising SAMe or a salt thereof in an amount of between 5 to 95% by weight, preferably between 20% to 60% by weight, relative to the weight of the composition in combination with an alkalizing agent and one or more pharmaceutical acceptable excipients.

The chewable tablet comprising SAMe or a salt thereof of the invention, wherein the alkalizing agent is selected from the list of meglumine, magnesium hydroxide, magnesium silicate, sodium carbonate, sodium bicarbonate, magnesium oxide, sodium citrate, tris (hydroxymethyl) aminomethane, meglumine mixture of acrylic resin, preferably meglumine is used.

In another general aspect, there is provided a chewable tablet composition comprising SAMe or a salt thereof in combination with meglumine and one or more pharmaceutically acceptable excipients.

In another general aspect, the weight ratio of active ingredient such as SAMe or a salt thereof to meglumine is between in the range of about 1:1 to about 1:30, preferably about 1:20.

Magnesium aluminometasilicate can be described by the chemical formula Al2O3.MgO2SiO2.H2O and preferably the aluminium oxide is present in the range of from 25% to 40%, the magnesium oxide present in the range of from 10% to 15%, and the silicon dioxide is present in the range of from 25% to 40%. As a substance that absorbs moisture, these percentages are based on drying the substance at 1100C for 7 hours. In a preferred aspect of the invention the magnesium aluminometasilicate may be Neusilin™ as produced by Fuji Chemical use as a moisture repelling agent.

In another general aspect, there is provided a chewable tablet composition comprising sulpho-adenosyl-L-methionine (SAMe) or a salt thereof in combination with magnesium aluminometasilicate and one or more pharmaceutically acceptable excipients, wherein the said magnesium aluminometasilicate present in an amount not more that about 10% w/w of the weight of composition.

In another general aspect, the weight ratio of SAMe or a salt thereof to magnesium aluminometasilicate is between in the range of about 1:1 to about 1:30, preferably about 1:12.

In another general aspect, there is provided a chewable tablet composition comprising sulpho-adenosyl-L-methionine (SAMe) or a salt thereof in combination meglumine in an amount of about 1.80% w/w of the total weight of tablet and not more that about 10% w/w of magnesium aluminometasilicate. The said tablet further comprises one or more pharmaceutically acceptable excipients.

In one embodiment, a chewable dosage form for oral administration consisting of SAMe or a salt thereof, meglumine, magnesium aluminometasilicate and one or more pharmaceutically acceptable excipients.

In another embodiment, a chewable tablet comprising SAMe or a salt thereof in an amount of between 5% to 95% by weight, preferably between 30 and 40% by weight, relative to the weight of the composition, in combination with meglumine in an amount of between 0.01% to 30% by weight, preferably between 0.5% to 15% by weight, relative to the weight of the composition and one or more pharmaceutical acceptable excipients.

In another embodiment, a chewable tablet comprising SAMe or a salt thereof in an amount of between 30% to 40% by weight in combination with meglumine in an amount of between 0.5% to 15% by weight and not more that 10% w/w of magnesium aluminometasilicate. The said composition according to embodiment further comprises one or more pharmaceutically acceptable excipients.

In another embodiment, a compositions comprising SAMe or a salt thereof in an amount of between 30% to 40% by weight relative to the weight of the composition, in combination with meglumine in an amount of between 0.5% and 15% by weight, relative to the weight of the composition.

In another embodiment, a chewable tablet composition comprising sulpho-adenosyl-L-methionine or a salt thereof in combination meglumine in an amount of about 1.80% w/w of the total weight of tablet and not more that about 10% w/w of magnesium aluminometasilicate.

In another embodiment, the ratio of meglumine to magnesium aluminometasilicate is in between about 0.5:1 to 0.5:3.

In another embodiment, a process for the preparation of a chewable tablet, wherein the process comprises step of:
a) preparing a mixture containing SAMe or a salt thereof, meglumine, sweetener;
b) granulate with binder solution to form granules;
c) drying the granules;
d) sizing the dried granules and adding one or more pharmaceutical acceptable excipients;
e) the said lubricated granules formulating further in a solid oral chewable dosage form.

In another embodiment, a process for the preparation of a chewable tablet, wherein the process comprises step of:
a) preparing a mixture containing SAMe or a salt thereof, magnesium aluminometasilicate, sweetener;
b) granulate with binder solution to form granules;
c) drying the granules;
d) sizing the dried granules and adding one or more pharmaceutical acceptable excipients;
e) the said lubricated granules formulating further in a solid oral chewable dosage form.

DETAILED DESCRIPTION OF THE INVENTION

According to the invention, "SAMe" is understood to mean either the racemic mixture or the individual diastereomers (RS)-(+)-S-adenosyl-L-methionine [(RS)-(+)-SAMe)] and (SS)-(+)-S-adenosyl-L-methionine [(SS)-(+)-SAMe)], including mixtures different from the racemic one. Preferably, said SAMe or a salt thereof is S-adenosylmethionine Disulfate p-Toluenesulfonate.

The pharmaceutically acceptable excipients used in the composition according to the invention are preferably selected from but not limited to diluents, disintegrants, binders, alkalizer, stabilizer, moisture repelling agent, fillers, bulking agents, anti-adherants, carriers, flavoring agents, plasticizers, lubricants, solubilizers, glidants, and the like known to the art used either alone or in combination thereof. It will be appreciated that certain excipients used in the composition can serve more than one purpose.

Diluents increase the bulk of a solid pharmaceutical composition. The term "diluent" will be understood by the skilled person to include a material that is primarily used in oral solid dosage forms as inert filler. Exemplary diluents for solid compositions include, but are not limited to microcrystalline cellulose, microfine cellulose, lactose, starch, pregelatinized starch, calcium carbonate, calcium sulfate, sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, kaolin, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, polymethacrylates, potassium chloride, powdered cellulose, sodium chloride, sorbitol, talc and mixture thereof.

Preferably, the compositions of the invention comprise from 5% to 50% w/w of diluent, based on the total weight of the composition. Preferred diluents are mannitol, F-melt, sorbitol, xylitol, microcrystalline cellulose, silicified microcrystalline cellulose, cellulosic polymers, such as hydroxypropylmethylcellulose and hydroxypropylcellulose.

Solid pharmaceutical compositions that are compacted into a dosage form, such as a tablet, may include excipients whose functions include helping to bind the active ingredient and other excipients together after compression. Exemplary binders for solid pharmaceutical compositions include, but are not limited to, ethyl cellulose, acacia, alginic acid, carbomer, carboxymethylcellulose sodium, dextrin, gelatin, guar gum, hydrogenated vegetable oil, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, liquid glucose, magnesium aluminum silicate, maltodextrin, methylcellulose, polymethacrylates, povidone, pregelatinized starch, sodium alginate, starch or combinations thereof.

Disintegrants may be selected from but are not limited to sodium starch glycolate, alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, croscarmellose sodium, crospovidone, guar gum, magnesium aluminum silicate, methyl cellulose, microcrystalline cellulose, polacrilin potassium, powdered cellulose, pregelatinized starch, sodium alginate and starch.

Glidants can be added to improve the flowability of a non-compacted solid composition and to improve the accuracy of dosing. The incorporation of the inert glidant of the compositions of the invention ensures satisfactory and reproducible content uniformity by ensuring acceptable blend homogeneity during processing. Exemplary excipients that may function as glidants include glyceryl monostearate, glyceryl behenate, glyceryl palmitostearate, colloidal silicon dioxide, magnesium trisilicate, powdered cellulose, starch, talc, tribasic calcium phosphate and mixtures thereof.

Preferably, the compositions of the invention comprise from 0.5% to 15% w/w of glidant, such as talc, more preferably from 0.8% to 12% w/w, based on the total weight of the composition.

A lubricant can be added to the composition to reduce adhesion. Exemplary lubricants include, but are not limited to, magnesium stearate, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc and zinc stearate.

The sweetener is added in the amount sufficient to achieve a desired sweetness. The sweeteners may be chosen from the following non-limiting list: glucose, dextrose, invert sugar, fructose, and combinations thereof, saccharin and its various salt such as the sodium salt; artificial sweeteners such as Neotame, aspartame, acesulfame K, cyclamates; chloro derivatives of sucrose such as sucralose; sugar alcohols such as sorbitol, mannitol, xylitol and other sweeteners well-known to those of skill in the art. Typically, the total amount of sweetener(s) is present in the chewable tablet composition from about 0.01% to about 3.5%.

The particular excipient used depends on the means and the purpose for which the active ingredient is applied.

The advantages obtained with the composition according to the invention are evident since all of them allow an easy and pleasant administration, do not require water to swallow and therefore can be taken anywhere, do not present problems of swallowing and are suitable both for acute and prolonged treatment.

Since the active principle dissolves and get absorbed through saliva its passage in the blood is very quick (few minutes) avoiding the first-pass metabolism and increasing the bio-availability which in turn permits lower dosage.

The chewable tablets according to the invention can be easily prepared according to the techniques and methods known in the art for this kind of products.

If the use of granulation becomes necessary to improve the properties of the mixture, the preferred method is the wet granulation that can be performed in a tabletting machine and in a rapid mixture granulator.

In another general aspect, the invention provides a process for the preparation of a chewable tablet according to the invention comprising wet granulation method wherein the active pharmaceutical ingredient are granulated together with an alkalizing agent; a moisture repelling agent and one or more pharmaceutically acceptable excipients.

In another general aspect, the invention provides a process for the preparation of a chewable tablet, wherein the process comprises step of preparing a mixture containing SAMe or a salt thereof, alkalizing agent, sweetener and granulate with binder solution to form granules, drying the granules, sizing the dried granules and adding one or more pharmaceutical acceptable excipients. The said lubricated granules formulating further in a solid oral chewable dosage form.

In another general aspect, the invention provides a process for the preparation of a chewable tablet, wherein the process comprises step of preparing a mixture containing SAMe or a salt thereof, moisture repelling agent, sweetener and granulate with binder solution to form granules, drying the granules, sizing the dried granules and adding one or more pharmaceutical acceptable excipients. The said lubricated granules formulating further in a solid oral chewable dosage form.

In another general aspect, the invention provides a process for the preparation of a chewable tablet, wherein the process comprises step of preparing a mixture containing SAMe or a salt thereof, alkalizing agent, moisture repelling agent, sweetener and granulate with binder solution to form granules, drying the granules, sizing the dried granules and adding one or more pharmaceutical acceptable excipients. The said lubricated granules formulating further in a solid oral chewable dosage form.

In another general aspect, the invention provides a process for the preparation of a chewable tablet, wherein the process comprises step of preparing a mixture containing SAMe or salt thereof, alkalizer such as meglumine, moisture repelling agent such as magnesium aluminometasilicate, aspartame and granulate with binder solution to form granules, drying the granules, sizing the dried granules and adding one or more pharmaceutical acceptable excipients. The said lubricated granules formulating further in a solid oral chewable dosage form.

As used herein, the term "composition" is intended to encompass a product comprising the specified ingredients, as well as any product which results, directly or indirectly, from combining the specified ingredients.

The term "chewable tablet" as used herein refers to a solid dosage form administered by mouth.

The term "pharmaceutically acceptable excipient" as used herein is intended to denote any material, which is inert in the sense that it substantially does not have any therapeutic and/or prophylactic effect per se. Such an excipient may be added with the purpose of making it possible to obtain a pharmaceutical composition, which has acceptable technical properties.

The term "disintegrant" refers to a substance added to the dosage form to help it break apart (disintegrate) and release the medicinal agent(s).

The invention relates to a chewable tablet of SAMe or a salt thereof comprising an alkalizing agent; a moisture repelling agent and one or more pharmaceutically acceptable excipients, which improves composition in terms of a simple, easy to operate, stable quality, controllable, reproducible, low cost, simple production process, good bioavailability and stability.

In one embodiment, a chewable tablet composition comprising sulpho-adenosyl-L-methionine (SAMe) or a salt thereof; an alkalizing agent and one or more pharmaceutically acceptable excipients.

In another embodiment, a chewable tablet composition comprising sulpho-adenosyl-L-methionine (SAMe) or a salt thereof; an moisture repelling agent and one or more pharmaceutically acceptable excipients.

In another embodiment, a chewable dosage form for oral administration consisting of SAMe or a salt thereof, an alkalizing agent, a moisture repelling agent and one or more pharmaceutically acceptable excipients.

In another embodiment, the moisture repelling agent is magnesium aluminometasilicate.

In another embodiment, a chewable tablet comprising SAMe or a salt thereof in an amount of between 5% to 95% by weight, preferably between 30 and 40% by weight, relative to the weight of the composition, in combination with an alkalizing agent in an amount of between 0.01% to 30% by weight, preferably between 0.5% to 15% by weight, relative to the weight of the composition and one or more pharmaceutical acceptable excipients.

In another embodiment, a chewable tablet comprising SAMe or a salt thereof in an amount of between 30% to 40% by weight in combination with an alkalizing agent in an amount of between 0.5% to 15% by weight and not more that 10% w/w of magnesium aluminometasilicate. The said composition according to embodiment further comprises one or more pharmaceutically acceptable excipients.

In another embodiment, a chewable tablet composition comprising sulpho-adenosyl-L-methionine or a salt thereof in combination with meglumine and one or more pharmaceutically acceptable excipients.

In another embodiment, a compositions comprising SAMe or a salt thereof in an amount of between 5% to 95% by weight, preferably between 30% to 40% by weight, relative to the weight of the composition, in combination with meglumine in an amount of between 0.01% to 30% by weight, preferably between 0.5% and 15% by weight, relative to the weight of the composition.

In another embodiment, a chewable tablet composition comprises sulpho-adenosyl-L-methionine or a salt thereof in combination meglumine in an amount of about 1.80% w/w of the total weight of tablet and not more that about 10% w/w of magnesium aluminometasilicate.

In another embodiment, the ratio of meglumine to magnesium aluminometasilicate is in between about 0.5:1 to 0.5:3.

In another embodiment, the one or more pharmaceutically acceptable excipients are selected from diluents, disintegrants, binders, alkalizer, moisture repelling agent, stabilizers, fillers, bulking agents, anti-adherants, carriers, flavoring agents, plasticizers, lubricants, solubilizers, glidants or mixture thereof.

In another embodiment, a chewable tablet of the invention comprises from 5% to 50% w/w of diluent based on the total weight of the composition.

In another embodiment, the chewable tablet of the invention comprises from 0.5% to 15% w/w of glidant, such as talc, more preferably from 0.8 to 5% w/w, based on the total weight of the composition.

In another embodiment, the chewable tablet of the invention comprises the total amount of disintegrant from about 0.1% to about 4.5%.

In another embodiment, the chewable tablet of the invention comprises the total amount of one or more sweetener from about 0.01% to about 3.5%.

In another embodiment, a process for the preparation of a chewable tablet, wherein the process comprises step of:
a) preparing a mixture containing SAMe or a salt thereof, alkalizing agent, sweetener;
b) granulate with binder solution to form granules;
c) drying the granules;
d) sizing the dried granules and adding one or more pharmaceutical acceptable excipients;
e) the said lubricated granules formulating further in a solid oral chewable dosage form.

In another embodiment, a process for the preparation of a chewable tablet, wherein the process comprises step of:
a) preparing a mixture containing SAMe or a salt thereof, moisture repelling agent such as magnesium aluminometasilicate, sweetener;
b) granulate with binder solution to form granules;
c) drying the granules;
d) sizing the dried granules and adding one or more pharmaceutical acceptable excipients;
e) the said lubricated granules formulating further in a solid oral chewable dosage form.

In another embodiment, the invention provides a process for the preparation of a chewable tablet, wherein the process comprises step of:
(a) preparing a mixture containing SAMe or a salt thereof, an alkalizing agent, a moisture repelling agent and sweetener
(b) granulating the mixture of step (a) with binder solution comprising ethyl cellulose and glyceryl behenate in suitable granulating solvent to form granules, (c) drying the granules, sizing the dried granules and adding one or more pharmaceutical acceptable excipients and
(d) formulating the blend of step (c) it further in a solid oral chewable tablet.

In another embodiment, the invention provides a process for the preparation of a chewable tablet, wherein the process comprises step of preparing a mixture containing SAMe or a salt thereof, meglumine, magnesium aluminometasilicate, aspartame and granulate with binder solution to form granules, drying the granules, sizing the dried granules and adding one or more pharmaceutical acceptable excipients. The said lubricated granules formulating further in a solid oral chewable dosage form.

Packaging of hygroscopic materials will protect the contents for long periods of time against moisture, deterioration and furthermore spoilage. Suitable packaging materials for chewable tablets according to the invention are selected from, but not limited to: aluminum/aluminum blisters, PVC/PVDC blisters and HDPE (high density polyethylene bottles). Preferably Formpack® Dessiflex™ Plus is used as a packaging material.

The chewable tablet of SAMe or a salt thereof may retain at least 90% by weight of the total content of SAMe when stored at 40°C and 75% relative humidity over a period of at least 3 months.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

The invention is further illustrated by the following examples which are provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the invention.

Examples 1-4: SAM-e Chewable Tablet

Sr. No. Name of Ingredients Unit qty. (% w/w)
Formula 1 Formula 2 Formula 3 Formula 4
1. S-Adenosyl L-methionine
Disulfate P-Toluenesulfonate 35.67 35.54 35.54 35.54
2. Heavy Magnesium oxide 5.11 5.09 5.09 5.09
3. Meglumine 1.85 1.85 1.39 2.31
4. Neusillin US2 2.78 2.77 2.59 2.95
5. Aspartame 0.93 0.92 0.92 0.92
6. Ethyl cellulose 10 cps 4.08 4.06 4.06 4.06
7. Glyceryl Behenate 1.30 1.29 1.29 1.29
8. Mannitol SD 200 36.89 36.75 37.40 36.10
9. F-Melt 1.85 1.85 1.85 1.85
10. Neotame 0.23 0.23 0.23 0.23
11. Sodium Chloride 2.27 2.26 2.26 2.26
12. Sodium Starch glycolate 2.78 2.77 2.77 2.77
13. Sylloid 1 FP 1.85 1.85 1.85 1.85
14. Orange Tang flavour 0.5 0.37 0.37 0.37
15. Talc 1.02 1.02 1.02 1.02
16. Mg. Stearate 1.39 1.39 1.39 1.39
Total 100% 100% 100% 100%

Manufacturing Process:

The chewable tablet pharmaceutical composition was prepared in four parts. The first part consists of S-Adenosyl L-methionine Disulfate P-Toluenesulfonate, magnesium oxide, meglumine, neusillin and aspartame. All these ingredients were sieved and premixed in rapid mixture granulator for 5 minuets. The second part consists of binder solution preparation containing ethyl cellulose and glyceryl behenate in suitable granulating solvent. The first part dry mixture in rapid mixture granulator was granulated till suitable consistent granulate formed. The dried granules was passed through sieve number #30 (600?m). The third part prepared by mixing mannitol, F-Melt, sodium starch glycollate, sylloid, sodium chloride, neotame, flavour and talc. The second part granules were mixed with third part material in octagonal blender for 20 minutes at slow speed. The final granules were lubricated with magnesium stearate and lubricated blend was compressed into tablets using suitable tooling. The said chewable tablet then packed in blister pack of Formpack Dessiflex Plus. The process is carried out in an environment in which the relative humidity is below 25% and the temperature is maintained between 15°C and 30°C, preferably at about 25°C.

Stability Data of Formula I
Sr. No. Content Condition % Assay Water By Kf %Dissolution
1hr 0.1N HCl
1 SAMe Disulfate p-Toluenesulfonate Initial 100.3 1.51 30mins- 66%
45mins- 89%
60mins- 103%
2 1M 40ºC/75%RH 100.6 1.63 30mins- 65%
45mins- 88%
60mins- 103%
4 3M 40ºC/75%RH 98.6 1.75 30mins- 60%
45mins- 81%
60mins- 97%
4 6M 40ºC/75%RH 98.1 1.90 30mins- 60%
45mins- 85%
60mins- 97%
,CLAIMS:1. A chewable tablet pharmaceutical composition comprising sulpho-adenosyl-L-methionine (SAMe) or a salt thereof, an alkalizing agent and one or more pharmaceutically acceptable excipients, wherein the said alkalizing agent is meglumine.

2. The chewable tablet pharmaceutical composition according to claim 1, wherein the composition further comprises a moisture repelling agent.

3. The chewable tablet pharmaceutical composition according to claim 2, wherein the moisture repelling agent is magnesium aluminometasilicate.

4. The chewable tablet pharmaceutical composition according to claims 1-3, wherein said SAMe salt is S-adenosylmethionine Disulfate p-Toluenesulfonate.

5. The chewable tablet pharmaceutical composition according to claims 1-3, wherein the SAMe is in an amount ranging from about 20% to 60% by weight relative to the weight of the composition.

6. The chewable tablet pharmaceutical composition according to claims 1-5, wherein the meglumine is present in an amount ranging from about 0.5% to 15% by weight, relative to the weight of the composition.

7. The chewable tablet pharmaceutical composition according to claim 3, wherein the magnesium aluminometasilicate is present in an amount of not more that about 10% w/w of the total composition.

8. The chewable tablet pharmaceutical composition according to claim 1, wherein the weight ratio of SAMe or a salt thereof to meglumine is in the range of about 1:1 to about 1:30.

9. A chewable tablet pharmaceutical composition comprising,
(a) 30% to 40% SAMe or a salt thereof,
(b) 0.5% to 15% meglumine,
(c) not more that 10% w/w of magnesium aluminometasilicate,
(d) 3-8% magnesium oxide and optionally,
(e) one or more pharmaceutically acceptable excipients.

10. A process of preparing chewable tablet composition according to claims 1-8, wherein said process comprising the steps of: (a) preparing a mixture containing SAMe Disulfate p-Toluenesulfonate (SAMe), an alkalizing agent, a moisture repelling agent, and sweetener, (b) granulating the mixture of step (a) with binder solution comprising ethyl cellulose and glyceryl behenate in suitable granulating solvent to form granules, (c) drying the granules, sizing the dried granules and adding one or more pharmaceutical acceptable excipients, and (d) formulating the blend of step (c) further in a solid oral chewable tablet.