TECHNICAL FIELD OF THE INVENTION
The present invention relates to dispersible pharmaceutical tablet compositions of therapeutically active aliphatic amine polymers and salts thereof. More specifically this invention relates to dispersible pharmaceutical tablet composition comprising hydrochloride and carbonate salt of the aliphatic amine polymers such as sevelamer hydrochloride and carbonate; optionally with one or more pharmaceutically acceptable excipient(s). The said tablet compositions are designed to disintegrate rapidly, thus eliminating the need to chew the tablet or swallow an intact tablet. The dispersible tablets are taken with minimal quantity of liquid, thus enhancing patient compliance. The present invention also provides process for the preparation of such compositions and method of treatment of patients suffering from chronic kidney disease such as hyperphosphatemia or a disease or condition associated with chronic kidney disease.
BACKGROUND OF THE INVENTION
Chronic kidney disease (CKD) is a worldwide public health problem. It is recognized as a common condition that is associated with an increased risk of cardiovascular disease and chronic renal failure (CRT). Chronic kidney disease occurs when one suffers from gradual and usually permanent loss of kidney function over time. This happens gradually, usually months to years. With loss of kidney function, there is an accumulation of water; waste; and toxic substances, in the body, that are normally excreted by the kidney and most individuals in this stage of kidney disease need dialysis or transplantation to stay alive. Factors that may cause progressive renal injury include the following: systemic hypertension, acute insults from nephrotoxins or decreased perfusion, proteinuria, increased renal ammoniagenesis with interstitial injury, hyperlipidemia, hyperphosphatemia with calcium phosphate deposition, decreased levels of nitrous oxide and smoking. Hyperphosphatemia frequently accompanies diseases associated with inadequate renal function, hyperparathyroidism, and certain other medical conditions due to the increased concentration of inorganic phosphates in the blood serum. Hyperphosphatemia is typically defined for humans as a serum phosphate level of greater than about 6.0 mg/dL of the normal adult range. The condition, especially if present over
extended periods of time, leads to severe abnormalities in calcium and phosphorus metabolism and can be manifested by aberrant calcification in joints, lungs and eyes.
Patients of chronic renal failure are unavoidably treated by dialysis normally at regular intervals over a prolonged period of time, and pathological conditions of increased plasma phosphate concentrations (6.0 mg/dl or more), i.e., hyperphosphatemia often appeared in the patients. Because no direct etiological treatment of hyperphosphatemia has been developed so far, diet therapy to lower phosphate absorption, or as a symptomatic therapy, treatment by oral administration of a medicament for hyperphosphatemia which adsorbs phosphate ions in the digestive tract has been generally applied.
To date, high phosphorus serum levels are treated with vitamin D or substances, which, when administered by oral route, bind phosphorus through chelating action (phosphorus binders) and eliminate it by fecal route. Although effective in their action of eliminating phosphorus, some of these substances must be avoided because of their side effects. For example, substances containing calcium, magnesium or aluminium are avoided by those experts in the field. These calcium salts when ingested binds to the intestinal phosphate to form insoluble calcium phosphate salts such as calcium hydrogen phosphate, calcium dihydrogen phosphate or tricalcium phosphate and thus prevents the phosphate absorption. However, the drawback associated with this mode of treatment is that due to absorption of high amount of ingested calcium, the patient develops hypercalcemia which in turn results in cardiac arrhythmias, renal failure and skin and visceral calcification.
Aliphatic amine polymers are useful as active pharmaceutical ingredients for use in many pharmaceutical compositions. Aliphatic amine polymers have also been used in the treatment of chronic kidney diseases such as hyperphosphatemia. Such polymeric materials bind or otherwise sequester a target molecule, such as a phosphate ion, provide an effective treatment for decreasing the serum level of phosphate, without concomitantly increasing the absorption of any clinically undesirable materials.
A particularly interesting aliphatic amine polymer is Sevelamer, an epichlorohydrin cross-linked poly(allylamine), disclosed in U.S. Pat. No. 5,496,545, which is incorporated by reference herein which is a polymeric phosphate binder intended for oral administration. The aliphatic amine polymer is available in the form of both carbonate and the hydrochloride salts (HC1) that are useful in the treatment of chronic kidney disease such as hyperphosphatemia. Instant invention deals with Sevelamer hydrochloride and carbonate. Sevelamer HC1 is poly(allylamine hydrochloride) crosslinked with epichlorohydrin in which forty percent of the amines are protonated. It is known chemically as poly(allylamine-co-N,N'-diallyl l,3-diamino-2-hydroxypropane) hydrochloride. Sevelamer hydrochloride is hydrophilic, but insoluble in water. Sevelamer carbonate is a polymeric amine that binds phosphate and is meant for oral administration. It is known chemically as poly (allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) carbonate salt. Sevelamer carbonate is hygroscopic, but insoluble in water. Structure of Sevelamer carbonate is represented below:
(Figure Removed)
Currently, sevelamer hydrochloride and sevelamer carbonate are being marketed under the trade name of Renagel® and Renvela® respectively. The recommended starting dose of sevelamer is 800 mg to 1600 mg. The high dose and the hygroscopic nature of sevelamer make it difficult to formulate it in a suitable dosage form.
The use of sevelamer and its pharmaceutical compositions, and processes for its preparation are disclosed in U.S. Patent No. 5,496,545.
US publication 20060251614 discloses tablet compositions comprising a carbonate salt of an aliphatic amine polymer and monovalent anion can prevent or ameliorate acidosis, in particular acidosis in patients with renal disease. The tablets and compositions of the present invention maintain a disintegration time of no greater than 30 minutes at 37degree C. and at pH of at least 1 for a period of at least ten weeks at 60.degree. C.
US patent bearing patent no. 7748036 discloses pharmaceutical compositions comprising aliphatic amine polymers such as for example Sevelamer HC1 as the active pharmaceutical ingredient, wherein the aliphatic amine polymers are spray granulated.
US publication 20090155368 discloses crosslinked polyamine particles and/or pharmaceutical compositions comprising, at least in part, crosslinked polyamine particles and aggregates of such particles (including cured aggregates of crosslinked polyamine particles) and may be in the form of tablets comprising, for example, particles larger than 500 .mu.m, and used for treating patients.
US patent bearing patent no. 6383518 discloses a tablet comprising a phosphate-binding polymer which has an average particle size of 400 µm or less, contains particle size of 500 urn or less in size at a ratio of 90% or more, and has a moisture content of 1 % to 14%, together with crystalline cellulose and/or low substituted hydroxypropylcellulose, said phosphate-binding polymer being a polymer selected from a specific group. Further, it discloses that crystalline cellulose and low- substituted hydroxypropyl cellulose are desired to obtain a tablet disintegration time of less than 15 minutes, which is not
obtained by using additives other than low- substituted hydroxypropyl cellulose or crystalline cellulose.
PCT publication 2009034540 discloses a pharmaceutical composition for oral administration comprising: a) less than about 80% w/w of sevelamer or pharmaceutically acceptable salts thereof; and b) pharmaceutically acceptable inert excipients; wherein the composition is free of crystalline cellulose and low-substituted hydroxypropyl cellulose.
US publication 20070190135 discloses a tablet preparation comprising particles of a phosphate-binding polymer having an average particle size of no more than 400 microns, with at least 90% of the particles being occupied by particles no larger than 500 microns, and having a true specific gravity of 1.20-1.22 and a water content of 1-14%; and at least one of crystalline cellulose or low substituted hydroxypropyl cellulose wherein the crystalline cellular or the low substituted hydroxypropyl cellulose or mixture thereof is present in an amount of at least 10% of the weight of the phosphate-binding polymer.
US20100008988 discloses a core tablet comprising less than about 80% by weight of an aliphatic amine polymer, wherein the aliphatic amine polymer is selected from sevelamer hydrochloride, sevelamer carbonate and colesevelam hydrochloride.
However none of the above listed references disclose pharmaceutical compositions comprising sevelamer and its salts thereof specifically hydrochloride or carbonate in dispersible dosage form as disclosed in context of present invention that are specifically useful in treating chronic kidney disease such as hyperphosphatemia or other related conditions or diseases. The inventors of the instant invention have invested considerable intellectual efforts to solve the unmet medical need for development of dispersible tablet pharmaceutical compositions comprising sevelamer and its salts thereof optionally with one or more pharmaceutically acceptable excipient(s) that disintegrates rapidly with minimal quantity of water as compared to marketed film coated tablet and powder for oral suspension compositions thus providing optimal convenience to the patient.

The present invention provides safe and effective therapy and method of treatment of patients suffering from chronic kidney disease such as hyperphosphatemia or a disease or condition associated with hyperphosphatemia.
SUMMARY OF THE INVENTION
An aspect of the present invention relates to dispersible pharmaceutical tablet compositions comprising from about 0.1% w/w to about 95% w/w of sevelamer and salts thereof selected from group comprising sevelamer hydrochloride or sevelamer carbonate as an active agent(s), optionally with one or more pharmaceutically acceptable excipient(s), wherein at least 90% of the particles of sevelamer and salts thereof as an active agent(s) have particle size of not more than about 500µm; and wherein said tablet disintegrates rapidly with a disintegration time of less than about 3 minutes.
An aspect of the present invention relates to dispersible pharmaceutical tablet compositions comprising from about 45% to 85% w/w of sevelamer and salts thereof selected from group comprising sevelamer hydrochloride or sevelamer carbonate as an active agent(s); from about 2% to 15% by weight of disintegrants present intragranularly or extragranularly or both; and optionally from about 0.1 to 45% w/w of one or more pharmaceutically acceptable excipient(s), wherein at least 90% of the particles of sevelamer and salts thereof as an active agent(s) have particle size of not more than about 500µm; and wherein said tablet disintegrates rapidly with a disintegration time of less than about 3 minutes.
An aspect of the present invention relates to dispersible pharmaceutical tablet compositions comprising from about 45% to 85% w/w of sevelamer carbonate as an active agent(s); from about 2% to 15% by weight of disintegrants present intragranularly or extragranularly or both; and optionally from about 0.1 to 45% w/w of one or more pharmaceutically acceptable excipient(s), wherein at least 90% of the particles of sevelamer carbonate as an active agent(s) have particle size of not more than about 500µm; and wherein said tablet disintegrates with a disintegration time of less than about 3 minutes.
Another aspect of the present invention relates to dispersible pharmaceutical tablet compositions, wherein the drug to disintegrant ratio is from about 2:1 to about 50:1.
One aspect of the present invention is to provide a process for the preparation of such
pharmaceutical tablet compositions comprising the following steps:
i) sifting sevalamer hydrochloride or carbonate as active agent(s);
ii) optionally adding one or more pharmaceutically acceptable excipient(s); and
iii) compressing the mixture into suitably sized tablets.
In another aspect, the present invention provides a process for the preparation of such
pharmaceutical tablet compositions comprising the steps of:
i) sifting sevalamer hydrochloride or carbonate as active agent(s);
ii) mixing the active agent(s) with a diluent(s);
iii) optionally adding one or more pharmaceutically acceptable excipient(s);
iv) granulating the blend;
v) lubricating the blend or granules; and
vi) compressing the blend or granules into suitably sized tablets.
In another aspect, the present invention provides a process for the preparation of such
pharmaceutical tablet compositions comprising the steps of:
i) sifting sevalamer carbonate as active agent(s);
ii) mixing the active agent(s) with a diluent(s);
iii) optionally adding one or more pharmaceutically acceptable excipient(s);
iv) granulating the blend;
v) lubricating the blend or granules; and
vi) compressing the blend or granules into suitably sized tablets.
In yet another aspect, the present invention also relates to method of using such compositions which comprises administering to a patient in need thereof an effective amount of the composition.
Another aspect of the present invention is to provide a method of treatment in chronic kidney disease such as hyperphosphatemia or other related conditions or diseases by administering to a patient in need thereof a pharmaceutical composition of the present invention.
DETAILED DESCRIPTION OF THE INVENTION:
It is believed that one skilled in the art based upon the description herein utilize the present invention to its fullest extent. The following specific embodiments are to be construed as merely illustrative and not limitative of the remainder of the disclosure in any way whatsoever. The present invention satisfies the existing unmet medical need for development of pharmaceutical compositions for chronic kidney disease such as hyperphosphatemia or a disease or condition associated with the same that could differ the composition associated with the prior art.
The term "dispersible tablet" used elsewhere in the specification is defined as the tablet that disperses or disintegrates in less than about 5 minutes in the mouth before swallowing. Such a tablet disintegrates into smaller granules or melts in the mouth from a hard solid to a gel-like structure, allowing easy swallowing by patients. It shall be understood to a person skilled in the art that the "dispersible tablet" in the context of the present invention can also encompass effervescence generating agents such as carbonates, bicarbonates, acids and the like which help in the disintegration of the tablet.
The present invention relates to dispersible pharmaceutical tablet compositions comprising from about 0.1% w/w to about 95% w/w of sevelamer and salts thereof selected from group comprising sevelamer hydrochloride or sevelamer carbonate as an active agent(s), optionally with one or more pharmaceutically acceptable excipient(s), wherein at least 90% of the particles of sevelamer and salts thereof as an active agent(s) have particle size of not more than about 500µm; and wherein said tablet disintegrates rapidly with a disintegration time of less than about 3 minutes.
In an embodiment of the present invention is provided dispersible pharmaceutical tablet compositions comprising from about 45% to 85% w/w of sevelamer and salts thereof selected from group comprising sevelamer hydrochloride or sevelamer carbonate as an active agent(s); from about 2% to 15% by weight of disintegrants present intragranularly or extragranularly or both; and optionally from about 0.1 to 45% w/w of one or more pharmaceutically acceptable excipient(s), wherein at least 90% of the particles of sevelamer and salts thereof as an active agent(s) have particle size of not more than about 500µm; and wherein said tablet disintegrates rapidly with a disintegration time of less than about 3 minutes.
In an embodiment of the present invention is provided dispersible pharmaceutical tablet compositions comprising from about 45% to 85% w/w of sevelamer carbonate as an active agent(s); from about 2% to 15% by weight of disintegrants present intragranularly or extragranularly or both; and optionally from about 0.1 to 45% w/w of one or more pharmaceutically acceptable excipient(s), wherein at least 90% of the particles of sevelamer carbonate as an active agent(s) have particle size of not more than about 500µm; and wherein said tablet disintegrates with a disintegration time of less than about 3 minutes.
In an embodiment of the present invention is provided dispersible pharmaceutical tablet composition, wherein the drug to disintegrant ratio is from about 2:1 to about 50:1, preferably from about 4:1 to about 40:1. In another embodiment, atleast 90% of the particles of sevelamer carbonate as an active agent(s) have particle size of about 400um, preferably upto 250 µm.
Taste is an important parameter governing the patient compliance. Since the drug is administered in the form of dispersible tablet, the bitter/disagreeable taste of the drugs and unpleasant properties of grittiness remains in the oral cavity which causes difficulties in swallowing or causes patients to avoid their medication. The dispersible tablets of the present invention also tend to decrease the negative taste sensation of the drug sevelamer and its salts with the use of taste masking agents such as sweeteners and flavors which thus provide pleasant taste and mouth feel.
The dispersible pharmaceutical tablet compositions comprising sevelamer hydrochloride or sevelamer carbonate as active agent involves simple manufacturing procedure which avoids batch to batch process variations, consumes less time, and is cost effective, more economically viable and easy handled by patients. The dispersible pharmaceutical tablet compositions have the added advantage over the existing marketed tablet dosage forms (Renagel® 800 mg and Renvela® 800 mg) which are bulky in size, difficult to administer and swallow leading to decrease in patient compliance. Further, a critical finding of the present invention is to overcome the administration issues of marketed film coated tablets and powder for oral suspension dosage forms comprising 800 mg of sevelamer hydrochloride and sevelamer carbonate which require comparatively large volume of water (-30 to 250 ml). Moreover, patients require three times a day dosing of marketed film coated tablets and powder for oral suspension (~2.4g) which further increases the water intake. In general, patients suffering from chronic kidney disease are advised less uptake of water due to water overload in the kidney. The inventors of the present invention have invested intellectual efforts to overcome the administration issues by preparing dispersible compositions that are easy to dispense as they disintegrate rapidly in about 15 to 30 ml of water as compared to marketed film coated tablets and powder for oral suspension forms. This further tends to decrease the dose loss of the active ingredient which happens in marketed powder for oral suspension dosage forms as the drug particles get attached to the walls of the administration container which further requires more water to rinse the particles completely. The said compositions eliminates the need to swallow an intact tablet thus enhancing patient compliance which is a significant advancement as compared to the prior art.
In another embodiment of the present invention, the one or more pharmaceutically acceptable excipient(s) of the present invention are selected from but not limited to a group comprising diluents, lubricants, binders, disintegrants, viscosity modifiers, surfactants, anti-caking agents, thixotropic agents, anti-oxidants, colorants, flavoring agents, sweeteners, preservatives, glidants, chelating agents, plasticizers, vehicles, complexing agents, buffering agents, preservatives, suspending agents, viscosity enhancing agents and the like known to the art used either alone or in combination
thereof. Certain excipients used in the present composition can serve more than one purpose.
Suitable diluents useful in the present invention is selected from but not limited to a group comprising microcrystalline cellulose, lactose, starch, dibasic calcium phosphate, saccharides, calcium lactate, calcium carbonate, cellulose powder, pregelatinized starch, dextrates, dextrins, dextrose, fructose, kaolin, lactitol, mannitol, xylitol, sorbitol, sucrose, sodium chloride, polyethylene glycol, glycine, or bentonites and the like, or mixtures thereof. Examples of diluents include microcrystalline celluloses such as Avicel® PH101, Avicel® PH102, Avicel® PHI 12, Avicel® PH200, Avicel® PH301 and Avicel® PH302; lactose such as lactose monohydrate, lactose anhydrous and Pharmatose® DCL21, including anhydrous, monohydrate and spray dried forms; dibasic calcium phosphate such as Emcompress®; mannitol such as Pearlitol® SD200; starch; sorbitol; sucrose; glucose, and the like used either alone or in combination thereof.
Suitable binders useful in the present invention is selected from but not limited to a group comprising polyvinylpyrrolidone (e.g. PVP K-90 or PVP K-30), copovidone (e.g. Plasdone® S630), crospovidone (e.g. Polyplasdone XL, Polyplasdone XL-10, Kollidon-CL, Kollidon CL-M), cellulosic polymers (e.g. hydroxypropyl cellulose, hydroxypropylmethyl cellulose, or the like), gums such as xanthan, alginates such as sodium alginate, polyvinylacetate, and the like used either alone or in combination thereof.
The disintegrants useful in the present invention is selected from but not limited to a group comprising croscarmellose sodium such as Solutab®, Vivasol® and the like, starches such as maize starch, potato starch, starch 1500 and the like, modified starches such as sodium starch glycollate, carboxymethylstarches and the like, starch derivatives such as amylose and the like, pregelatinized starch, celluloses, cross-linked carboxymethylcellulose, crospovidone (e.g. Polyplasdone XL, Polyplasdone XL-10, Kollidon-CL, Kollidon CL-M), methacrylic acid-divinylbenzene copolymer salts such as Amberlite™ IRP88, clays, aliginic acid, alginates, gums, bicarbonates, carbonates, acids and the like used either alone or in combination thereof.
Suitable lubricants are selected from but not limited to a group comprising talc; stearic acid, stearates such as magnesium stearate, calcium stearate, zinc stearate; colloidal silicon dioxide such as Aerosil® 200; sodium stearyl fumarate, hydrogenated vegetable oil, glyceryl behenate, waxes and the like used either alone or in combination thereof.
In another embodiment of the present invention, the wetting agent useful in the present invention is a surfactant selected from but not limited to a group comprising anionic, cationic, nonionic or zwitterionic surfactant, or combinations thereof. Examples of suitable wetting agents include sodium lauryl sulphate, cetrimide, polyethylene glycols; polyoxyethylene-polyoxypropylene block copolymers known as poloxamer; polyglycerin fatty acid esters such as decaglyceryl monolaurate and decaglyceryl monomyristate; sorbitan fatty acid ester such as sorbitan monostearate (SPAN® 80); polyoxyethylene sorbitan fatty acid ester such as polyoxyethylene sorbitan monooleate (TWEEN® 80, TWEEN® 40); polyethylene glycol fatty acid ester such as polyoxyethylene monostearate; polyoxyethylene alkyl ether such as polyoxyethylene lauryl ether; polyoxyethylene castor oil and hardened castor oil, such as polyoxyethylene hardened castor oil; and the like used either alone or in combination thereof. Suitable sweeteners include sucrose, sucralose, saccharin, compressible sugar or aspartame, Cyclamate, Mannitol, Lactose, Sucrose, Dextrose, acesulfame potassium and mixtures thereof. Suitable anticaking agent useful in the present invention is selected from but not limited to a group comprising Sodium bicarbonate, Sodium ferrocyanide, Potassium ferrocyanide, Calcium ferrocyanide, Bone phosphate, Sodium silicate, Silicon dioxide, Calcium silicate, Magnesium trisilicate, Talcum powder, Sodium aluminosilicate, Potassium aluminium silicate, Calcium aluminosilicate, Bentonite, Aluminium silicate, Stearic acid, Polydimethylsiloxane, or mixtures thereof. Suitable anticaking agent useful in the present invention is amorphous silica. Suitable antioxidant is selected from but not limited to a group comprising ascorbic acid and their esters, alpha-tocopherol, ethylene diamine tetra acetic acid, sodium metabisulfite, sodium bisulfate, Butylated Hydroxy Toluene (BHT), Butylated Hydroxy Anisole (BHA), citric acid, and tartaric acid and the like. Suitable vehicle is selected from but not limited to a group comprising lactose, white
sugar, sodium chloride, glucose, starch, calcium carbonate, kaolin, microcrystalline cellulose, and silicic acid. Suitable plasticizer is selected from but not limited to a group comprising triethylcitrate, tributyl citrate, acetyl triethylcitrate, acetyl tributyl citrate and the like. Suitable glidant is selected from but not limited to a group comprising talc, magnesium stearate, stearic acid, zinc stearate, magnesium stearate, calcium stearate or hydrogenated castor oil and the like used either alone or in combination thereof.
The composition can be prepared by either direct compression, dry compression (slugging) or by granulation. The composition prepared by granulation technique is either by aqueous or non-aqueous technique or combination of both or melt granulation technique. The non-aqueous solvent used is selected from a group comprising dehydrated alcohol, isopropyl alcohol (IPA), methylene chloride or acetone.
In an embodiment of the present invention is provided a process for the preparation of
such oral dispersible compositions which comprises of the following steps:
i) sifting sevalamer hydrochloride or carbonate as active agent(s);
ii) optionally adding one or more pharmaceutically acceptable excipient(s); and
iii) compressing the mixture into suitably sized tablets.
In another embodiment of the present invention is provided a process for the preparation
of such oral dispersible compositions which comprises of the following steps:
i) sifting sevalamer hydrochloride or carbonate as active agent(s);
ii) mixing the active agent(s) with a diluent(s);
iii) optionally adding one or more pharmaceutically acceptable excipient(s);
iv) granulating the blend;
v) lubricating the blend or granules; and
vi) compressing the blend or granules into suitably sized tablets.
In another embodiment of the present invention is provided a process for the preparation of such pharmaceutical tablet compositions comprising the steps of: i) sifting sevalamer carbonate as active agent(s);
ii) mixing the active agent(s) with a diluent(s);
iii) optionally adding one or more pharmaceutically acceptable excipient(s);
iv) granulating the blend;
v) lubricating the blend or granules; and
vi) compressing the blend or granules into suitably sized tablets.
In yet another embodiment of the present invention is provided a method of using such compositions which comprises administering to a subject in need thereof an effective amount of the composition. In a further embodiment, the composition of the present invention may be useful for the management such as prophylaxis, amelioration or treatment of chronic kidney disease such as hyperphosphatemia or other related conditions or diseases associated with same.
The foregoing examples are illustrative embodiments of the invention and are merely exemplary. A person skilled in the art may make variations and modification without depending from the spirit and scope of the invention. All such modification and variation are intended to be included within the scope of the invention as discussed in this specification.
EXAMPLES
Example-1
S. No. Ingredient mg/tablet
Intragranular
1. Sevelamer Carbonate 800
2. Crospovidone 65
3. Microcrystalline cellulose 107
4. Povidone K-90 65
5. IPA q.s Extragranular
6. Crospovidone 65
7. Microcrystalline cellulose 74

8. Sucralose 6.5
9. Sodium chloride 13
10. Zincstearate 13
11. Strawberry Flavor 6.5
Procedure:
i) Ingredient 1 was sifted.
ii) Ingredients 2 and 3 were mixed together and sifted.
iii) Ingredient 4 was dissolved in IPA to obtain a homogeneous solution.
iv) The material of step (i) and (ii) were mixed together.
v) The material of step (iv) was granulated with the material of step (iii) followed by
drying and sifting, vi) Ingredients 6, 7, 8, 9, 10 and 11 were passed through a sieve of mesh size 30 and
mixed together with material of step (v). vii) Ingredients of step (vi) were compressed to form tablet.
(Table Removed)
Example-2
S. No. Ingredient mg/tablet
Intragranular
1. Sevelamer Carbonate 800
2. Crospovidone 65
3. Microcrystalline cellulose 107
4. Povidone K 30 65
5. IPA q.s
Extragranular
6. Crospovidone 65
7. Microcrystalline cellulose 74
8. Aspartame 13
9. Sodium chloride 13
10. Magnesium stearate 13
11. Strawberry Flavor 6.5
Procedure:
i) Ingredient 1 was sifted.
ii) Ingredients 2 and 3 were mixed together and sifted.
iii) Ingredient 4 was dissolved in IPA to obtain a homogeneous solution.
iv) The material of step (i) and (ii) were mixed together.
v) The material of step (iv) was granulated with the material of step (iii) followed by
drying and sifting, vi) Ingredients 6, 7, 8, 9, 10 and 11 were passed through a sieve of mesh size 30 and
mixed together with material of step (v). vii) Ingredients of step (vi) were compressed to form tablet.
(Table Removed)
Example-3
S. No. Ingredient mg/tablet
Intragranular
1. Sevelamer Carbonate 800
2. Crospovidone 65
3. Microcrystalline cellulose 181
4. Povidone K-90 65
5. IPA q.s
6. Purified water q.s Extragranular
7. Crospovidone 65
8. Sucralose 6.5
9. Sodium chloride 13
10. Zinc stearate 13
11. Strawberry Flavor 6.5
Procedure:
i) Ingredient 1 was sifted.
ii) Ingredients 2 and 3 were mixed together and sifted.
iii) Ingredient 4 was dissolved in a mixture of IPA and Purified water to obtain a
homogeneous solution, iv) The material of step (i) and (ii) were mixed together, v) The material of step (iv) was granulated with the material of step (iii) followed by
drying and sifting, vi) Ingredients 7, 8, 9, 10 and 11 were passed through a sieve of mesh size 30 and
mixed together with material of step (v). vii) Ingredients of step (vi) were compressed to form tablet.
(Table Removed)

Example-4
S. No. Ingredient mg/tablet
Intragranular
1. Sevelamer Carbonate 800
2. Crospovidone 65
3. Povidone K 30 65
4. IPA q.s
Extragranular
5. Crospovidone 65
6. Microcrystalline cellulose 238
7. Sucralose 6.5
8. Sodium chloride 13
9. Zinc stearate 13
10. Strawberry Flavor 6.5 Procedure:
i) Ingredients 1 and 2 were sifted and mixed together.
ii) Ingredient 3 was dissolved in IPA to obtain a homogeneous solution.
iii) The material of step (i) was granulated with the material of step (ii) followed by
drying and sifting, iv) Ingredients 5, 6,7,8,9 and 10 were passed through a sieve of mesh size 30 and
mixed together with material of step (iii). v) Ingredients of step (iv) were compressed to form tablet.
(Table Removed)
Example-5
S. No. Ingredient mg/tablet
Intragranular
1. Sevelamer Carbonate 800
2. Crospovidone 130
3. Povidone K 30 65
4. IPA q.s
5. Purified water q.s Extragranular
6. Microcrystalline cellulose 238

7. Sucralose 6.5
8. Sodium chloride 13
9. Zinc stearate 13
10. Strawberry Flavor 6.5
Procedure:
i) Ingredients 1 and 2 were sifted and mixed together.
ii) Ingredient 3 was dissolved in a mixture of IPA and Purified water to obtain a
homogeneous solution, iii) The material of step (i) was granulated with the material of step (ii) followed by
drying and sifting, iv) Ingredients 6, 7, 8, 9 and 10 were passed through a sieve of mesh size 30 and
mixed together with material of step (iii). v) Ingredients of step (iv) were compressed to form tablet.
(Table Removed)

Example-6
S. No. Ingredient mg/tablet
Intragranular
1. Sevelamer Carbonate 800
2. Povidone K 30 65
3. IPA q.s

4. Purified water q.s Extragranular
5. Microcrystalline cellulose 303
6. Crospovidone 130
7. Sucralose 6.5
8. Sodium chloride 13

9. Zinc stearate 13
10. Strawberry Flavor 6.5 Procedure:
i) Ingredient 1 was sifted.
ii) Ingredient 2 was dissolved in a mixture of IPA and Purified water to obtain a
homogeneous solution, iii) The material of step (i) was granulated with the material of step (ii) followed by
drying and sifting, iv) Ingredients 5, 6, 7, 8, 9 and 10 were passed through a sieve of mesh size 30 and
mixed together with material of step (iii). v) Ingredients of step (iv) were compressed to form tablet.
(Table Removed)

Example-7
S. No. Ingredient mg/tablet
Intragranular
1. Sevelamer Hydrochloride 800
2. Crospovidone 65
3. Microcrystalline cellulose 120
4. Povidone K 30 65
5. IPA q.s
Extragranular
6. Crospovidone 65
7. Microcrystalline cellulose 74
8. Aspartame 13
9. Magnesium stearate 13
10. Strawberry Flavor 6.5 Procedure:
i) Ingredient 1 was sifted.
ii) Ingredients 2 and 3 were mixed together and sifted.
iii) Ingredient 4 was dissolved in IPA to obtain a homogeneous solution.
iv) The material of step (i) and (ii) were mixed together.
v) The material of step (iv) was granulated with the material of step (iii) followed by
drying and sifting, vi) Ingredients 6, 7, 8, 9 and 10 were passed through a sieve of mesh size 30 and
mixed together with material of step (v). vii) Ingredients of step (vi) were compressed to form tablet.
(Table Removed)

We claim:
1. A dispersible pharmaceutical tablet composition comprising from about 0.1% w/w to about 95% w/w of sevelamer and salts thereof selected from group comprising sevelamer hydrochloride or sevelamer carbonate as an active agent(s), optionally with one or more pharmaceutically acceptable excipient(s), wherein at least 90% of the particles of sevelamer and salts thereof as an active agent(s) have particle size of not more than about 500um; and wherein said tablet disintegrates rapidly with a disintegration time of less than about 3 minutes.
2. The composition as claimed in claim 1, comprising from about 45% to 85% w/w of sevelamer and salts thereof selected from group comprising sevelamer hydrochloride or sevelamer carbonate as an active agent(s); from about 2% to 15% by weight of disintegrants present intragranularly or extragranularly or both; and optionally from about 0.1 to 45% w/w of one or more pharmaceutically acceptable excipient(s), wherein at least 90% of the particles of sevelamer and salts thereof as an active agent(s) have particle size of not more than about 500µm; and wherein said tablet disintegrates rapidly with a disintegration time of less than about 3 minutes.
3. The composition as claimed in claim 1 or 2, comprising from about 45% to 85% w/w of sevelamer carbonate as an active agent(s); from about 2% to 15% by weight of disintegrants present intragranularly or extragranularly or both; and optionally from about 0.1 to 45% w/w of one or more pharmaceutically acceptable excipient(s), wherein at least 90% of the particles of sevelamer carbonate as an active agent(s) have particle size of not more than about 500µm; and wherein said tablet disintegrates with a disintegration time of less than about 3 minutes.
4. The composition as claimed in claims 1 to 3, wherein the drug to disintegrant ratio is from about 2:1 to about 50:1.
5. The composition as claimed in claims 1 to 4, wherein the one or more pharmaceutically acceptable excipient(s) of the present invention are selected from a group comprising diluents, lubricants, binders, disintegrants, viscosity modifiers, surfactants, anti-caking agents, thixotropic agents, anti-oxidants, colorants, flavoring agents, sweeteners, preservatives, glidants, chelating agents,
plasticizers, vehicles, complexing agents, buffering agents, preservatives, suspending agents, viscosity enhancing agents used either alone or in combination thereof.
6. The composition as claimed in claim 5, wherein the diluent is selected from a group comprising microcrystalline cellulose, lactose, starch, dibasic calcium phosphate, saccharides, calcium lactate, calcium carbonate, cellulose powder, pregelatinized starch, dextrates, dextrins, dextrose, fructose, kaolin, lactitol, mannitol, xylitol, sorbitol, sucrose, sodium chloride, polyethylene glycol, glycine, bentonites or mixtures thereof; the binder is selected from a group comprising polyvinylpyrrolidone, copovidone, crospovidone, cellulosic polymers, gums, alginates, polyvinylacetate used either alone or in combination thereof; the disintegrant is selected from a group comprising croscarmellose sodium, starches, modified starches, starch derivatives, pregelatinized starch, celluloses, cross-linked carboxymethylcellulose, crospovidone, methacrylic acid-divinylbenzene copolymer salts, clays, aliginic acid, alginates, gums, bicarbonates, carbonates, acids used either alone or in combination thereof; the lubricant is selected from a group comprising talc; stearic acid, stearates such as magnesium stearate, calcium stearate, zinc stearate; colloidal silicon dioxide such as Aerosil® 200; sodium stearyl fumarate, hydrogenated vegetable oil, glyceryl behenate, waxes used either alone or in combination thereof.
7. A process of preparation of the composition as claimed in claim 1, which comprises of the following steps:
i) sifting sevalamer hydrochloride or carbonate as active agent(s);
ii) optionally adding one or more pharmaceutically acceptable excipient(s); and
iii) compressing the mixture into suitably sized tablets.
8. A process of preparation of the composition as claimed in claim 7, which
comprises of the following steps:
i) sifting sevalamer hydrochloride or carbonate as active agent(s);
ii) mixing the active agent(s) with a diluent(s);
iii) optionally adding one or more pharmaceutically acceptable excipient(s);
iv) granulating the blend;
v) lubricating the blend or granules; and
vi) compressing the blend or granules into suitably sized tablets.
9. A process of preparation of the composition as claimed in claim 7, which
comprises of the following steps:
i) sifting sevalamer carbonate as active agent(s);
ii) mixing the active agent(s) with a diluent(s);
iii) optionally adding one or more pharmaceutically acceptable excipient(s);
iv) granulating the blend;
v) lubricating the blend or granules; and
vi) compressing the blend or granules into suitably sized tablets.
10. The pharmaceutical compositions and processes for the preparation of
pharmaceutical compositions substantially as herein described and illustrated by
the examples.