This application claims priority to Indian patent application No. 1897/CHE/2010 filed on July 05,2010 and 3639/CHE/2010 filed on December 01, 2010, the contents of which are incorporated by reference in their entirety.

FIELD OF THE INVENTION

The present invention relates to an improved process for the preparation of Sevelamer or its pharmaceutically acceptable salts thereof.

BACKGROUND OF THE INVENTION

Sevelamer is a phosphate binding polymer indicated for the control of serum phosphorus in patients with Chronic Kidney Disease (CKD) on hemodialysis. It binds phosphorus in the gastrointestinal tract to facilitate phosphorus excretion in feces, by inhibiting phosphorus absorption from the gut, and thereby lowering the plasma phosphorus concentration.

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 to 1600 mg. The high dose and the hygroscopic nature of Sevelamer make it difficult to formulate it in a suitably dosage form.

Cross-linked polyallylamine polymers having therapeutic applications include Sevelamer hydrochloride, Sevelamer carbonate are indicated for the control of serum phosphorus in patients with Chronic Kidney Disease (CKD) on hemodialysis. They are available in tablet form for oral use. These polymers are used to treat high blood levels of phosphorous in patients [hyperphosphatemia]. It binds phosphorous and prevents it from being absorbed into the blood stream. By binding phosphate in the gastrointestinal tract, Sevelamer hydrochloride and Sevelamer carbonate lowers the phosphate concentration in the serum.

The structure of Sevelamer hydrochloride, Sevelamer carbonate is shown below in Structural Formulae (I &II): The primary amine groups shown in the structure are derived directly from poly(allylamine hydrochloride). The crosslinking groups consist of two secondary amine groups derived from poly(allylamine hydrochloride) and one molecule of epichlorohydrin.

US 4,528,347 patent discloses a process for producing a polymer of monoallylamine or a salt thereof by polymerizing an inorganic monoallylamine acid salt in a polar solvent in the presence of an azo type initiator and further converted to crossed linked polymers.

U.S. Pat. No. 4,605,701 discloses a process for preparing cross-linked polymer wherein cross- linking is performed with partially neutralized aqueous solution of polyallylamine using liquid medium that is immiscible with aqueous solvents. One of the difficulties in this process is that this process employs aliphatic or aromatic hydrocarbons for use as the liquid medium. The difficulty is that the polymerization process results in a high volume of effluents making the process difficult in terms of operation and batch cycle time. Since the polymerization occurs in heterogeneous immiscible phases, achieving consistency in the cross-linked product would depend upon number of process parameters such as mixing. It is highly important to have consistency in product quality to meet the requirements of drug product. Hence there is need to improve the process which would give product of consistent quality.

U.S. Pat. No. 6,083,495 covers an aqueous process to make Sevelamer hydrochloride from the polyallylamine hydrochloride. It uses an aqueous alkaline solution for making the cross- linked polyallylamine, wherein the polyallylamine is reacted with a difunctional cross-linking agent in an aqueous alkaline solution to get the cross-linked polymer gel. Cross-linking in aqueous medium is associated with issues such as solubility of cross-linking agent as well as stoichiometric adjustment to achieve desired level of cross-linking.

U.S. Pat. No. 6,180,754 covers a process to make Sevelamer hydrochloride using a special type of reactor known as LIST reactor. It discloses a process for producing a cross-linked polyallylamine polymer by reacting a reduced salt, aqueous solution of a polyallylamine polymer with a multifunctional cross-linking agent in a special LIST reactor to give a cross-linked polyallylamine polymer.

U.S. Pat. No. 6,362,266 discloses a method for producing a cross-linked polyallylamine polymer by (a) reacting an aqueous solution of a polyallylamine polymer with a multifunctional cross- linking agent to give a cross-linked polyallylamine polymer; (b)
washing this aqueous solution of cross-linked polyallylamine polymer with an alcohol/ water solution; (c) adding a surfactant to the washed cross-linked polyallylamine polymer; (d) drying the cross-linked polyallylamine polymer; (e) grinding and sieving the cross-linked polyallylamine polymer; and (f) isolating the cross-linked polyallylamine polymer.

U.S. Pat. No. 6,600,011 relates to methods for purifying and drying an organic polymer hydrogel by washing the polymer hydrogel with a water wash medium and then spray drying the resulting slurry.

These aforementioned methods to produce cross-linked polymers have several disadvantages such as for the removal of generated sodium chloride in the process, extra water washings are required & extra washings leads to the bulging (enlargement) of Sevelamer HC1 gel since it absorbs the water and swells up to 15 times, which ultimately affect on efficiency & productivity during Industrial scale. Achieving desired industrial scale and consistency in product quality. Also the cross-linked product obtained from known methods requires intensive purification to produce desired quality of product on industrial scale. Hence, there is a need to provide an improved process for the preparation of cross-linked amine polymers which can overcome the above mentioned drawbacks.

OBJECT AND SUMMARY OF THE INVENTION

The main object of the present invention relates to an improved process for the preparation of Sevelamer or its pharmaceutically acceptable salts thereof.

In one object, the present invention relates to an improved process for the preparation of
Sevelamer or its pharmaceutically acceptable salts thereof, which comprises;

(a) dissolving polyallylamine hydrochloride in a mixture of water and organic solvent,
(b) adjusting pH with base,
(c) optionally adding a phase transfer catalyst,
(d) adding epichlorohydrin and
(e) isolating Sevelamer hydrochloride and optionally converting into pharmaceutically acceptable salts thereof.

In another object, the present invention relates to an improved process for the preparation of Sevelamer or its pharmaceutically acceptable salts thereof, which comprises;

(a) suspending polyallylamine hydrochloride in a mixture of water and organic solvent,
(b) adjusting pH with base,
(c) optionally adding a phase transfer catalyst,
(d) reacting with epichlorohydrin and
(e) isolating Sevelamer hydrochloride and optionally converting into pharmaceutically acceptable salts thereof.

In yet another object, the present invention relates to a process for the preparation of Sevelamer and pharmaceutically acceptable salts comprising the steps of dissolving polyallylamine hydrochloride in water and neutralizing by appropriate base. This reaction mass was added with an organic solvent and distilled out for two to three times to remove the water. Filtering the inorganic salts and concentrating the filtrate obtains a residue. Optionally a phase transfer catalyst is added. The residue was added with water and polyallylamine hydrochloride followed by addition of an organic solvent, epichlorohydrin and water and cooling the reaction mass, filtering and drying results in Sevelamer hydrochloride.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is an X-ray powder diffraction (XRD) pattern of amorphous Sevelamer hydrochloride.

DETAILED DESCRIPTION OF THE IVENTION

The present invention provides an improved process for the preparation of Sevelamer or its pharmaceutically acceptable salts thereof.

In one embodiment, the present invention provides an improved process for the preparation of Sevelamer or its pharmaceutically acceptable salts thereof comprising the steps of:

(a) dissolving polyallylamine hydrochloride in a mixture of water and organic solvent,
(b) adjusting pH with base,
(c) optionally adding a phase transfer catalyst,
(d) adding epichlorohydrin and
(e) isolating Sevelamer hydrochloride and optionally converting into pharmaceutically acceptable salts thereof.

According to the present invention, polyallylamine hydrochloride is dissolved in a mixture of water and organic solvent selected from hydrocarbons such as cyclohexane, toluene or alcohols such as n-butanol followed by adjustment of pH to basic by using a base selected from sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide. The resultant reaction mass is optionally added with a phase transfer catalyst followed by addition of crosslinking agent such as epichlorohydrin. The solid thus obtained is filtered and dried to obtain Sevelamer hydrochloride which is then optionally converted to other pharmaceutically acceptable salts.

According to the present invention, the pH is adjusted to basic pH in the range of about 10 to 12 using 20% to 60% sodium hydroxide solution. The resultant reaction mass is optionally added with a phase transfer catalyst and heated to about 50 to 60°C. Epichlorohydrin is added to the reaction mass and maintained for about 3 to 5 hours.

Cooling the reaction mass to the room temperature separates the solid which is then washed with alcoholic solvent such as isopropyl alcohol and water to afford Sevelamer Hydrochloride.

In another embodiment, the present invention provides an improved process for the preparation of Sevelamer or its pharmaceutically acceptable salts thereof comprising the steps of:

(a) suspending polyallylamine hydrochloride in a mixture of water and organic solvent,
(b) adjusting pH with base,
(c) optionally adding a phase transfer catalyst,
(d) reacting with epichlorohydrin and
(e) isolating Sevelamer hydrochloride and optionally converting into pharmaceutically acceptable salts thereof.

According to the present invention, polyallylamine hydrochloride is suspended in a mixture of water and organic solvent selected from hydrocarbons such as cyclohexane, toluene or alcohols such as n-butanol followed by adjustment of pH to basic by using a base such as sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide. The resultant reaction mass is optionally added with a phase transfer catalyst followed by addition of epichlorohydrin. The solid thus obtained is separated, filtered and dried to obtain Sevelamer hydrochloride which is then optionally converted to other pharmaceutically acceptable salts.

According to the present invention, the phase transfer catalyst is selected from tetrabutyl ammonium chloride, tetrabutyl ammonium bromide, benzyl triethyl ammonium chloride, benzyl tributyl ammonium chloride, Tetrabutyl ammonium hydroxide, Tetrabutyl ammonium hydrogen sulphate, etc.

In yet another embodiment, the present invention provides a process for the preparation Sevelamer or its pharmaceutically acceptable salts thereof, comprises the steps of:

a) dissolving polyallyl amine hydrochloride in water or mixture of water and orangic solvent,
b) neutralizing polyallyl amine hydrochloride,
c) removing the inorganic salts,
d) optionally adding a phase transfer catalyst,
e) adding a cross linking agent, and
f) isolating Sevelamer or its pharmaceutically acceptable salt.

According to the present invention, polyallylamine hydrochloride is dissolved in water and neutralized partially or completely using an appropriate base such as metal hydroxides like sodium hydroxide, potassium hydroxide, magnesium hydroxide or calcium hydroxide and carbonates like sodium carbonate, potassium carbonate and bicarbonates like sodium bicarbonate, potassium bicarbonate the like. The resultant solution is added with an organic solvent such as alcohols (like methanol, ethanol, isopropyl alcohol, butanol) or hydrocarbon (like toluene, cyclohexane, heptane, etc) or alkyl ester (like ethyl acetate, methyl acetate, etc.) or nitrile (like acetonitrile or propionitrile, etc.) or ethers (like tetrahydro furan, methyl tert-butyl ether, etc.) or ketone (like acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.) and removed by distillation thus removing the water present in the reaction mixture. Further adding an organic solvent as mentioned above and cooling the reaction mixture to lower temperature results in the precipitation of inorganic salts. Filtering the salts and concentrating the filtrate results in reaction mass. Optionally a phase transfer catalyst is added. Adding required amount of Polyallylamine HC1, water and organic solvent such as hydrocarbon (like toluene, xylene, cyclohexane, n-heptane, hexane etc) or alkyl ester (like ethyl acetate, methyl acetate, etc.) or nitrile (like acetonitrile or propionitrile, etc.) or ethers (like tetrahydro furan, methyl tert-butyl ether, etc.) or ketone (like acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.) to the reaction mass and heating from minimum 40 to 70 or its reflux temp followed by addition of epichlorohydrin and maintaining for about 2 to 6 hours followed by cooling the reaction mixture results in the precipitation of Sevelamer Hydrochloride which is washed with water and isopropyl alcohol and dried.

Preferably the polyallylamine acid salt polymer is neutralized prior to crosslinking. Neutralization can be accomplished with suitable base such as ammonium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate preferably sodium hydroxide. Preferably, the polyallylamine acid salt polymer is neutralized whereby at least about 60% to about 100%. Neutralization of polyallylamine hydrochloride with sodium hydroxide on commercial scale, results in formation of copious quantity of sodium chloride. Salt such as sodium chloride is undesirable in the final cross linked polyallylamine for the use in therapeutic applications. In the present invention, removal of salt, such as sodium chloride, prior to cross linking eliminated the tedious and costly process of removing the salt from the cross-linked polymer. Polyallylamine polymer after removal of salt again mixed with suitable quantity of polyallylamine hydrochloride preferably equivalent to the required % of chloride in the crosslinked polyallylamine.

Normally the inorganic salts formed in the reaction mixture are removed by giving more number of water washings. The more number of water washings results in swelling of the gel material to a tune of about 8 to 15 times. The present invention helps in reducing the number of water washings by filtering the precipitated inorganic salts. As the number of water washing are reduced, the gel material will not swell as given in the prior art process.

This mechanism of filtering the inorganic salts by reducing the number of water washings and maintaining the swelling of the gel material within the limits makes this process industrially feasible thus saving time and cost.

According to the present invention, epichlorohydrin is added at a temperature 45 to 60°C.
According to the present invention, the final product is washed with water and alcoholic solvent such as isopropyl alcohol and dried in Fluid Bed dryer.

Yet another embodiment of the present invention provides an improved process for the preparation of Sevelamer or its pharmaceutically acceptable salts thereof, wherein polyallylamine hydrochloride is subjected to setting free of acid in the presence of base and reacted with epichlorohydrin in the solvent or mixture of solvents in the optional presence of a phase transfer catalyst to give Sevelamer hydrochloride.

According to the present invention, the amorphous Sevelamer hydrochloride disclosed in the present invention is confirmed by PXRD pattern shown in Fig. 1.

According to one more embodiment of the present invention, Sevelamer hydrochloride is optionally converted into Sevelamer or it's pharmaceutically acceptable salts thereof.
Sevelamer hydrochloride is granular in nature and hence easily filtered, effectively washed and dried and hence easily scalable, optionally converted into pharmaceutically acceptable salts, which is having phosphate binding capacity 4.0 to 6.5 mMole/g & Chloride content between 16.0 to 20.0% w/w.

The present process is helpful in maintaining the chloride content in the required range as well decreases the number of water washings thus making the process industrially feasible. The processes disclosed in the present invention are industrially feasible and easy to practice at industrial level. The invention is further illustrated by the following non-limiting examples.

Examples
Example 1: Preparation of Polyallylamine HC1
Con. HC1 solution (212.0g) was charged to RB flask at 25-30°C & cooled to 0-5°C. Allylamine (100 gm) was added slowly to the flask. Temperature was raised to 25-30°C. 2,2'-Azobis-(2-methyl propionamidine) dihydrochloride (4.0 gm) was added to the reaction mass at 25-30°C under Nitrogen (N2) atmosphere. Reaction mass was stirred for 30 min. at 25-30°C. Reaction mass was then heated to 50±3°C and maintained for 6.0 hrs., (2.0 gm) 2,2'-Azobis-(2-methyl propionamidine) dihydrochloride was added to the reaction mass and maintained for next 18 hrs. Again (3.0 gm) 2,2'-Azobis-(2-methyl propionamidine) dihydrochloride was added and maintained for next 44 hrs at 50±3°C. In another flask 2500ml methanol was charged & above solution was slowly added to the methanol. Material was filtered under Nitrogen blanketing, bed washing with methanol (200ml) and dried under vacuum drier at 40-45 °C for 24 hrs to get 160g white polyallyl amine Hydrochloride.

Example-2: Preparation of Sevelamer HC1
Polyallylamine HC1 (200 gm) was charged into RB flask at 25-30°C. 150 ml of Water was charged to the above flask and dissolved it completely. Sodium hydroxide (38 g) was dissolved in 150ml water and this solution was added slowly to the above flask. The reaction mixture was maintained for 30 mins. at 25-30°C. Cyclohexane (600ml) was charged to the reaction mass and heated to 35±3°C. Heat the reaction mass, Epichlorohydrin (15.34 gm) was added to the reaction mass at 53±3°C. Stirring was maintained for 3-4 hrs at 53±3°C. Water (800ml) was added to the reaction mass and stirred for 1 hr at 53±3°C. The reaction mass was cooled, added purified water, filter the reaction mass, wash the cake with Isopropyl alcohol, spin dry the material. Dry the material in FBD till LOD of the material is NMT 6.0%.

Example-3: Preparation of Sevelamer HC1100 gm of Polyallylamine HC1 was dissolved in 400 ml of water and cyclohexane (800 ml) at 25-30 °C. pH was adjusted to 10-10.5 by adding 20% Sodium hydroxide solution. The reaction mixture was maintained for 30 mins. 10.4 gm of Tetrabutyl ammonium chloride was added to the reaction mass. Stirred for 10 min, reaction mass was heated to -50 °C. 11.8 gm of Epichlorohydrin was added to the reaction mass at 50 °C. Reaction mass was maintained for 3-4 hrs at 50 °C. The reaction mass was cooled to 25-30°C. Solid was filtered and washed with Isopropyl alcohol followed by water. Dry the material in Fluid Bed dryer at 40 - 60°C.
Dry wt. ~ 75 g.

Example-4: Preparation of Sevelamer HC1
100 gm of Polyallylamine HC1 was dissolved in 400 ml of water and Toluene (800 ml) at
25-30 °C. pH was adjusted to 10-10.5 by adding 20% Sodium hydroxide solution. The
reaction mixture was maintained for 30 mins. 12.0 gm of Tetrabutyl ammonium bromide
was added to the reaction mass. Stirred for 10 min, reaction mass was heated to 50±5 °C.
11.8 gm of Epichlorohydrin was added slowly to the reaction mass at 50±5 °C. Reaction
mass was maintained for 3-4 hrs at 50±5 °C. The reaction mass was cooled to 25-30°C.
Solid was filtered and washed with Isopropyl alcohol followed by water.
Dry the material in Fluid Bed dryer at 40 - 60°C.
Dry wt. ~ 75 g.

Example-5: Preparation of Sevelamer HC1
100 gm of Polyallylamine HC1 was dissolved in 300 ml of water and Cyclohexane (800
ml) at 25-30 °C. pH was adjusted to 10-10.5 by adding 20% Sodium hydroxide solution.
The reaction mixture was maintained for 30 mins. 12.0 gm of Tetrabutyl ammonium
bromide was added to the reaction mass. Stirred for 10 min, reaction mass was heated to
50±5 °C. 11.8 gm of Epichlorohydrin was added slowly to the reaction mass at 50±5 °C.
Reaction mass was maintained for 3-4 hrs at 50±5 °C. The reaction mass was filtered and
sluried in Isopropyl alcohol and washed with water followed by Isopropyl alcohol
washing. Dried the material in Fluid Bed dryer at 40 - 80°C.
Dry wt. ~ 75 g.

Example-6:
100 gm of Polyallylamine HC1 was dissolved in 400 ml of water and n-Butanol (800 ml)
at 25-30 °C. pH was adjusted to 10-10.5 by adding 20% Sodium hydroxide solution. The
reaction mixture was maintained for 30 mins. 12.0 gm of Tetrabutyl ammonium bromide
was added to the reaction mass. Stirred for 10 min, reaction mass was heated to 50±5 °C.
11.8 gm of Epichlorohydrin was added slowly to the reaction mass at 50±5 °C. Reaction
mass was maintained for 3-4 hrs at 50±5 °C. The reaction mass was cooled to 25-30°C.
Solid was filtered and washed with Isopropyl alcohol followed by water.
Dry the material in Fluid Bed dryer at 40 - 60°C.
Dry wt. ~ 75 g.

Example-7:
100 gm of Polyallylamine HC1 was dissolved in 300 ml of water and Cyclohexane (800
ml) at 25-30 °C. pH was adjusted to 10-10.5 by adding 20% Sodium hydroxide solution.
The reaction mixture was maintained for 30 mins. 12.0 gm of Benzyl tributyl ammonium
chloride was added to the reaction mass. Stirred for 10 min, reaction mass was heated to
50±5 °C. 11.8 gm of Epichlorohydrin was added slowly to the reaction mass at 50±5 °C.
Reaction mass was maintained for 3-4 hrs at 50±5 °C. The reaction mass was filtered and
sluried in Isopropyl alcohol and washed with water followed by Isopropyl alcohol
washing. Dried the material in Fluid Bed dryer at 40 - 80°C.
Dry wt. ~ 75 g.

Example-8:
100 gm of Polyallylamine HC1 was dissolved in 300 ml of water and Cyclohexane (800
ml) at 25-30 °C. pH was adjusted to 10-10.5 by adding 20% Sodium hydroxide solution.
The reaction mixture was maintained for 30 mins. 12.0 gm of Benzyl triethyl ammonium
chloride was added to the reaction mass. Stirred for 10 min, reaction mass was heated to
50±5 °C. 11.8 gm of Epichlorohydrin was added slowly to the reaction mass at 50±5 °C.
Reaction mass was maintained for 3-4 hrs at 50±5 °C. The reaction mass was filtered and
sluried in Isopropyl alcohol and washed with water followed by Isopropyl alcohol
washing. Dried the material in Fluid Bed dryer at 40 - 80°C.
Dry wt. ~ 75 g.

Example -9: Preparation of Sevelamer HC1
Polyallylamine HC1 (100 gm) was charged into RB flask at 25-30°C. 150 ml of Water was charged to the above flask and dissolved it completely. Sodium hydroxide (42.7g) was dissolved in 150ml water and this solution was added slowly to the above flask. The reaction mixture was maintained for 30 mins. at 25-30°C. Methanol (400ml) was added to reaction mass and distilled out under vacuum at 55±5°C, again Methanol (400ml) was added to reaction mass and distilled out under vacuum at 55±5°C. Methanol (1000 ml) was added to the reaction mass and cooled to 0-5°C, sodium chloride salt was removed by filtration and filtrate was concentrated to residue by vacuum distillation. Water (300ml) was added to reaction mass, Polyallylamine HC1 (35.6g) was charged to the reaction mass & reaction mass was stirred for 30 mins. Cyclohexane (600ml) was charged to the reaction mass and heated to 53±3°C. Epichlorohydrin (15.93 gm) was added to the reaction mass at 53±3°C. Stirring was maintained for 3-4 hrs at 53±3°C. Water (800ml) was added to the reaction mass and stirred for 1 hr at 53±3°C. The reaction mass was cooled to 25-30°C. Solid was filtered and washed with water (800ml) & Isopropyl alcohol (500 ml). The material was dried in Fluid Bed dryer at 40 - 60°C. Dry wt. - 110 g

We claim

1. A process for the preparation Sevelamer or its pharmaceutically acceptable salts
comprises the steps of

a) dissolving polyallyl amine hydrochloride in water or mixture of water and orangic solvent,
b) neutralizing polyallyl amine hydrochloride,
c) removing the inorganic salts,
d) optionally adding a phase transfer catalyst,
e) adding a cross linking agent, and
f) isolating Sevelamer or its pharmaceutically acceptable salt.

2. The process according to claim 1, wherein the organic solvent is selected from hydrocarbons such a cyclohexane, heptane, toluene or alcohols such as butanol.

3. A process according to claim 1, wherein the neutralizing agents are selected from sodium hydroxide, potassium hydroxide, magnesium hydroxide or calcium hydroxide and carbonates like sodium carbonate, potassium carbonate and bicarbonates like sodium bicarbonate, potassium bicarbonate.

4. The process according to claim 1, wherein the inorganic salts formed during the neutralization is removed by filtration.

5. The process according to claim 1, wherein the phase transfer catalyst is selected from tetrabutyl ammonium chloride, tetrabutyl ammonium bromide, benzyl triethyl ammonium chloride, benzyl tributyl ammonium chloride, tetrabutyl ammonium hydroxide, tetrabutyl ammonium hydrogen sulphate.

6. The process according to claim 1, wherein the cross linking agent is epichlorohydrin.

7. The process according to claims 1, wherein the epichlorohydrin is added at a temperature 45 to 60°C.

8. Sevelamer hydrochloride prepared according to claim 1 having at least one of the parameter selected from

a) Sevelamer hydrochloride having phosphate binding capacity of 4.0 to 6.5 mMole/g

b) Sevelamer hydrochloride having chloride content between 16.0 to 20.0% w/w

9. A process for the preparation of Sevelamer or its pharmaceutically acceptable salts thereof comprising the steps of:

(a) suspending polyallylamine hydrochloride in a mixture of water and organic solvent,
(b) adjusting pH with base,
(c) optionally adding a phase transfer catalyst,
(d) reacting with epichlorohydrin and
(e) isolating Sevelamer hydrochloride and optionally converting into pharmaceutically acceptable salts thereof.

10. A process for the preparation of Sevelamer hydrochloride by neutralizing
polyallylamine hydrochloride and filtering the resultant inorganic salts, adding required
amount of polyallylamine hydrochloride, heating the reaction mass and treating with an
crossliking agent, isolating Sevelamer hydrochloride having phosphate binding capacity
of 4.0 to 6.6mMole/g and chloride content between 16 to 20% w/w.