DESC:RELATED PATENT APPLICATION(S)
This application claims the priority to, and benefit of Indian Patent Application No. 202041023135 filed on June 02, 2020; the disclosures of which are incorporated herein by reference.
FIELD OF THE INVENTION:
The present invention relates to an improved process for the preparation of Sodium zirconium cyclosilicate. More specifically, the invention relates to an improved process for the preparation of ZS-9 crystal form of sodium zirconium cyclosilicate.

BACKGROUND OF THE INVENTION:
Sodium zirconium cyclosilicate has the chemical formula Na~1.5H~0.5ZrSi3O9•2–3H2O. Sodium zirconium cyclosilicate exists in different forms. Among other forms, ZS-9 form of sodium zirconium cyclosilicate exhibits a high capacity to selectively entrap monovalent cations specifically excess potassium and ammonium ions in gastrointestinal tract. The high specificity of ZS-9 form is due to the chemical composition and diameter of the micro pores. ZS-9 form of sodium zirconium cyclosilicate microporous ion exchangers is approved for the treatment of hyperkalemia. Sodium zirconium cyclosilicate is non-absorbed, odorless, insoluble powder.

The Product is first disclosed in the Patent US 5338527 and discloses a process for the preparation of the same thereof. There are different forms of sodium zirconium cyclosilicate disclosed in the Patent US5891417. Among the forms, ZS-9 form is particularly used for absorption of potassium and ammonium ions from the gastrointestinal tract. During the preparation of ZS-9 of Sodium zirconium cyclosilicate other undesired crystalline forms are also formed. The undesired forms have to be controlled during the manufacturing process itself since reprocessing the product is difficult as it is insoluble in all solvents.

The Patent US 9662352 discloses the preparation of Sodium zirconium cyclosilicate by hydrothermal crystallizing the reaction mixture prepared by combining zirconium acetate solution, source of silica, alkali metal hydroxide and water characterized by a specialized process and reactor configuration that lifts and more thoroughly suspends crystals throughout the reaction. This Patent also discloses the use and proper positioning of a baffle-like structure in relation to the agitator within the crystallization vessel and the cooling jacket comprising serpentine-type coils proximate to the outside wall of the reaction vessel in the reactor vessel to produces the desired ZS-9 form.
Besides the availability of process for the preparation of sodium zirconium cyclosilicate in state of the art, there is a need for an improved process for the preparation of pure sodium zirconium cyclosilicate ZS-9 form that is economically significant.

OBJECTIVES OF THE INVENTION:
The main objective of the present invention is to provide an improved process for the preparation of crystal form of Sodium zirconium cyclosilicate.

It is the objective of the present invention to provide an improved process for the preparation of ZS-9 crystal form of sodium zirconium cyclosilicate which is substantially free from the other forms such as ZS-7 and ZS-8.

Yet, it is the objective of the present invention to provide an improved process for the preparation of pure sodium zirconium cyclosilicate ZS-9 crystal form that is economically significant.

SUMMARY OF THE INVENTION:
Accordingly, the present invention discloses and describes an improved process for the preparation of Sodium zirconium cyclosilicate, more particularly ZS-9 crystal form of sodium zirconium cyclosilicate which is substantially free from the other forms such as ZS-7 and ZS-8.

A process for the preparation of sodium zirconium cyclosilicate crystal form ZS-9 which is substantially free of other forms ZS-7 and ZS-8, wherein the process is performed in a reactor.

In one embodiment, a pure sodium zirconium cyclosilicate ZS-9 form is obtained by the process of the invention described, which is economically significant.

One aspect of the present invention is to provide a process for the preparation of crystal form of sodium zirconium cyclosilicate in a reactor comprising the steps of:
(i) providing a mixture of sodium silicate solution and sodium hydroxide solution in the reactor;
(ii) applying nitrogen pressure to the mixture provided in step (i);
(iii) adding zirconium acetate solution to the mixture provided in step (ii);
(iv) stirring the reaction mixture obtained in step (iii) with the agitator at 100 to 1000 RPM in the reactor at temperatures above 175°C; and
(v) obtaining sodium zirconium cyclosilicate from the reactor,
wherein the reactor comprises:
- a reaction vessel having a volume of at least 2-L with an inside and outside wall;
- an agitator within the reaction vessel;
- a cooling jacket comprising serpentine-type coils proximate to the outside wall of the reaction vessel; or at least one baffle-like structure proximate the inside wall of the reaction vessel and placed in operative proximity to the agitator to provide uniform suspension of solids within the reaction vessel.

In one embodiment, the obtained sodium zirconium cyclosilicate is prepared in a reaction vessel having volume ranging about 2-L (2-Litre) to 5-L (5-Litre).

In one embodiment, the volume of reaction vessel in which the reaction is performed is at least about 2L (2-Litre).

In one embodiment, the volume of reaction vessel in which the reaction is performed is about 5L (5-Litre).

In one embodiment, the stirring of the reaction mixture in each step, is carried out in the range of 100 to 1000 RPM by using the agitator.

In one embodiment, the nitrogen pressure applied in step (ii) to the reaction mixture of step (i), is applied about 10 Kg.

In one embodiment, the stirring of the reaction mixture in step (iv) is carried out at temperature ranging between 210 °C to 250 °C.

In one embodiment, the stirring of the reaction mixture of step (iii) carried out in step (iv) may be carried out by the seeding crystalline ZS-9 material obtained from previous batches in the rection mixture.

In one embodiment, the pH of the reaction mass in step (v) is adjusted about 5 and about 6 by dilute acid. Preferably the obtained sodium zirconium cyclosilicate is washed with one or multiple washings with purified water.

A pure sodium zirconium cyclosilicate ZS-9 crystal form having the peaks pattern (2 Theta) as shown in PXRD of Figure-1 and Sodium zirconium cyclosilicate ZS-9 crystal form particle size distribution as shown in Figure-2 and the process as described below and in examples.

BRIEF DESCRIPTION OF DRAWING FIGURES:

Figure-1: The PXRD pattern of sodium zirconium cyclosilicate resulted in Example-1.
Figure-2: The Particle size distribution of sodium zirconium cyclosilicate resulted in Example-1.

DETAILED DESCRIPTION OF THE INVENTION:
Accordingly, in one aspect the present invention discloses and describes an improved process for the preparation of crystal form of Sodium zirconium cyclosilicate, more particularly ZS-9 form of sodium zirconium cyclosilicate which is substantially free from the other forms such as ZS-7 and ZS-8.

A pure sodium zirconium cyclosilicate ZS-9 form which is economically significant is prepared and provided.

In one embodiment the present invention provides a process for the preparation of crystal form of sodium zirconium cyclosilicate in a reactor comprising the steps of:
(i) providing a mixture of sodium silicate solution and sodium hydroxide solution in the reactor;
(ii) applying nitrogen pressure to the mixture provided in step (i);
(iii) adding zirconium acetate solution to the mixture provided in step (ii);
(iv) stirring the reaction mixture obtained in step (iii) with the agitator at 100 to 1000 RPM in the reactor at temperatures above 175°C; and
(v) obtaining sodium zirconium cyclosilicate from the reactor,
wherein the said reactor comprises:
- a reaction vessel having a volume of at least 2-L with an inside and outside wall;
- an agitator within the reaction vessel;
- a cooling jacket comprising serpentine-type coils proximate to the outside wall of the reaction vessel; or at least one baffle-like structure proximate the inside wall of the reaction vessel and placed in operative proximity to the agitator
to provide uniform suspension of solids within the reaction vessel.

Step (i)
Step (i) involves mixing a sodium silicate solution and sodium hydroxide solution in the reactor.
In one embodiment, the providing a mixture of sodium silicate solution and sodium hydroxide solution in the reactor according to the step (i) of the present invention is preferably done by adding sodium silicate solution to a solution of sodium hydroxide in the reactor and stirring the mixture in the range of 100 to 1000 RPM by using agitator.
Step (ii)
Step (ii) involves applying nitrogen pressure to the mixture provided in step (i). In one embodiment, preferably 10 Kg of nitrogen pressure was applied in step (ii) of the present invention and maintained during the step (iv).
Step (iii)
Step (iii) involves adding zirconium acetate solution to the mixture provided in step (ii). In one embodiment, the addition of zirconium acetate solution to the mixture according to the step (iii) of the present invention may be done directly into the reactor, preferably by slow addition of zirconium acetate in the reactor with stirring in the range of 100 to 1000 RPM by agitator.

Step (iv)
Step (iv) involves stirring the reaction mixture obtained in step (iii) with the agitator at 100 to 1000 RPM in the reactor at temperatures above 175°C.
In one embodiment the step of stirring the reaction mixture obtained in step (iii) according to the step (iv) is carried out in the range of 100 to 1000 RPM by the agitator for 20 to 50 hours at temperatures above 175°C, preferably above 200°C, more preferably in the range of 210°C to 250°C.
Preferably the step of stirring the reaction mixture obtained in step (iii) according to the step (iv) may be carried out after the seeding crystalline ZS-9 material obtained from previous batches in the reaction mixture.
Step (v)
Step (v) involves obtaining sodium zirconium cyclosilicate from the reactor. In one embodiment, preferably the pH of the reaction mass is adjusted to 5 to 6 by dilute acid solution after obtaining sodium zirconium cyclosilicate from the reactor as in step (v) of the present invention.
Preferably the obtained sodium zirconium cyclosilicate is washed with one or multiple washings with purified water.
Surprisingly the present inventors found that the process for achieving predominantly ZS-9 of sodium zirconium cyclosilicate from sodium silicate and zirconium acetate, could be performed either a cooling jacket comprising serpentine-type coils proximate to the outside wall of the reaction vessel; or at least one baffle-like structure proximate the inside wall of the reaction vessel and placed in operative proximity to the agitator, whereas the previous process as described in the prior art Patent US 9457050 ensures the presence of both the cooling jacket comprising serpentine-type coils proximate to the outside wall of the reaction vessel; and at least one baffle-like structure proximate the inside wall of the reaction vessel and placed in operative proximity to the agitator for achieving predominantly ZS-9 of sodium zirconium cyclosilicate from sodium silicate and zirconium acetate.
Unexpectedly the process of the present invention is achieved in smaller reaction vessels of volume such as 2L (2-Litre) and 5L (5-Litre) respectively whereas the prior art process as disclosed in the Patent US 9457050 is not suitable in smaller reaction vessels of volume lesser than 20 L (20-Litre).

The process of the present invention achieved in smaller reaction vessels of volume such as 2L (2-Litre) and 5L (5-Litre) could be achieved in large scale manufacturing of the product.

Preferably Sodium zirconium cyclosilicate resulted in the process of the present invention is the ZS-9 form of sodium zirconium cyclosilicate substantially free of the other forms such as ZS-7 and ZS-8.

A pure ZS-9 form of sodium zirconium cyclosilicate substantially free of the other forms such as ZS-7 and ZS-8.

The PXRD peaks pattern (2 Theta) of sodium zirconium cyclosilicate obtained in one example embodiment of present invention is shown in Figure-1.

The Particle size distribution of sodium zirconium cyclosilicate obtained in one example embodiment of present invention is shown in Figure-2 and the distribution result as shown below:

The present invention is explained in detail with reference to the following examples described below, which are given for the purpose of illustration only and are not intended to limit the scope of the invention.

Examples:

Example-1:
Sodium hydroxide solution (73.8 gm of sodium hydroxide in 920 ml of purified water) was added to 5L-autoclave reactor having an agitator within the reaction vessel and fitted with a cooling jacket having a serpentine configuration to provide a baffle-like structure within the reactor. Sodium silicate solution (568.4 gm) was added into the reactor at 150-200 RPM by the agitator for 30 minutes. Zirconium acetate (230 gm) was slowly into the reaction mixture at 150-200 RPM by the agitator for 40 minutes. The reactor was sealed; 10 Kg nitrogen pressure was applied; heated to 210°C-225°C and the reaction mixture was stirred at 150-200 RPM by the agitator at 20-30 kg pressure for 48 hours. After the completion of 48 hours, the reaction mass was cooled to 40°C± 5°C. The solid was filtered, slurried in purified water (920 ml) and stirred at 35°C for 30 minutes. The solid was then filtered and slurried in purified water (920 ml). The pH of the contents was adjusted to 5.0 to 6.0 by the dilute hydrochloric acid; stirred at 35°C for 30 minutes and filtered. The filtered solid was dried at 80°C under vacuum for 6 hours. Yield: 131.4 gm

Example-2:
Sodium hydroxide solution (38.32 gm of sodium hydroxide in 150 ml of purified water) was added to 2L-autoclave reactor having an agitator within the reaction vessel with baffle-like structure proximate the inside wall of the reaction vessel. Sodium silicate solution (206 gm) was added slowly into the reactor at 1000 RPM by the agitator for 40 minutes. Zirconium acetate (120 gm) was slowly into the reaction mixture at 1000 RPM by the agitator for 45 minutes. The reactor was sealed; 10 Kg nitrogen pressure was applied; heated to 210°C-225°C and the reaction mixture was stirred at 1000 RPM by the agitator at 20-30 kg pressure for 48 hours. After the completion of 48 hours, the reaction mass was cooled to 40°C± 5°C. The solid was filtered, washed in purified water (3600 ml) and dried at 80°C under vacuum. Yield: 62 gm

Example-3:
Sodium hydroxide solution (36.4 gm of sodium hydroxide in 460 ml of purified water) was added to 2L-autoclave reactor having an agitator within the reaction vessel and fitted with a cooling jacket having a serpentine configuration to provide a baffle-like structure within the reactor. Sodium silicate solution (284.22 gm) was added slowly into the reactor at 150-200 RPM by the agitator for 30 minutes. Zirconium acetate (115 gm) was slowly into the reaction mixture at 150-200 RPM by the agitator for 40 minutes. The product obtained in Example-1 was used as a seeding material (5.75 gm) and added in the reactor. Then the reactor was sealed; 10 Kg nitrogen pressure was applied; heated to 210°C-230°C and the reaction mixture was stirred at 150-200 RPM by the agitator at 20-30 kg pressure for 24 hours. After the completion of 24 hours, the reaction mass was cooled to 40°C± 5°C. The solid was filtered, slurried in purified water (460 ml) and stirred at 35°C for 1 hour. The solid was then filtered and slurried in purified water (460 ml). The pH of the contents was adjusted to 5.0 to 6.0 by the diliute hydrochloric acid; stirred at 35°C for 30 minutes and filtered. The filtered solid was dried at 85°C under vacuum for 6 hours. Yield: 68 gm
,CLAIMS:
1) A process for preparation of sodium zirconium cyclosilicate crystal form ZS-9 which is substantially free of other forms ZS-7 and ZS-8, wherein the process is performed in a reactor, comprising the steps of:
(i) mixing a sodium silicate solution and sodium hydroxide solution in the reactor;
(ii) applying nitrogen pressure to the mixture provided in step (i);
(iii) adding zirconium acetate solution to the mixture provided in step (ii);
(iv) stirring the reaction mixture obtained in step (iii) with the agitator at 100 to 1000 RPM in the reactor at temperatures above 175° C; and
(v) obtaining sodium zirconium cyclosilicate from the reactor;
wherein the said reactor comprises:
- a reaction vessel having a volume of at least 2-L with an inside and outside wall;
- an agitator within the reaction vessel;
- a cooling jacket comprising serpentine-type coils proximate to the outside wall of the reaction vessel; or at least one baffle-like structure proximate the inside wall of the reaction vessel and placed in operative proximity to the agitator to provide uniform suspension of solids within the reaction vessel.

2) The process as claimed in claim 1, wherein the obtained sodium zirconium cyclosilicate is prepared in a reaction vessel having volume ranging about 2-L to 5-L.

3) The process as claimed in claim 1, wherein the stirring of the reaction mixture in each step, is carried out in the range of 100 to 1000 RPM by using the agitator.

4) The process as claimed in claim 1, wherein about 10 Kg of nitrogen pressure is applied in step (ii).

5) The process as claimed in claim 1, wherein the stirring of the reaction mixture in step (iv) is carried out at temperature ranging between 210 °C to 250 °C.

6) The process as claimed in claim 1, wherein the stirring in step (iv) may be carried out by the seeding crystalline ZS-9 material obtained from previous batches in the rection mixture.

7) The process as claimed in claim 1, wherein the pH of the reaction mass in step (v) is adjusted about 5 and about 6 by dilute hydrochloric acid.