DESC:FIELD OF THE INVENTION
The present invention relates to a stable pharmaceutical composition of calcium polystyrene sulfonate. The pharmaceutical composition of calcium polystyrene sulfonate is in the form of a stable oral suspension. The present invention further relates to use of a stable oral suspension for the treatment of Hyperkalemia. The present invention also describes the preparation of such compositions in form of oral suspension.

BACKGROUND OF THE INVENTION
Potassium has many functions in the body. It helps to regulate the activity of all muscle tissue-smooth muscles (such as the muscles in the intestines), the muscles of the heart, and skeletal muscles. Potassium also plays a part in the enzymatic reactions involved in digestion and other metabolisms of the body. Potassium further plays a role in homeostasis, the mechanism used by the body to maintain a balance between the many electrical and chemical processes of the body.
Almost all (98%) of the potassium in the body is found inside cells (intracellular). Only about 2% occurs in the fluids outside of the cells (extracellular). Potassium can move into and out of cells as necessary to maintain the proper balance in the body. Blood tests reveal the extracellular potassium levels and are not indicative of the amount of intracellular potassium. Movement of potassium into or out of the cells can change the blood potassium level (serum potassium) when there is no change in the overall amount of potassium in the body.
Hyperkalemia occurs when the level of potassium in the bloodstream is higher than normal. This may be related to an increase in total body potassium or excessive release of potassium from the cells of the body into the bloodstream.
Sodium polystyrene sulfonate suspension, USP is an approved pharmaceutical product for the treatment of hyperkalemia. It can be administered orally or rectally (by enema). One current marketed formulation consists of several ingredients, including sorbitol solution, USP. This ingredient is used as a vehicle in the formulation. High density liquids such as sorbitol are often used in suspension formulations to increase physical stability. Recent literature indicates potential harmful gastrointestinal side effects with the concomitant use of sorbitol and sodium polystyrene sulfonate such as bleeding, hematochezia, colonic perforation, colonic necrosis and/or serpiginous ulcers. (Chaudhury, et al., American Journal of Kidney Diseases, Vol. 30, No. 1 (July) 1997: pp. 120-122; Gerstman, et al., American Journal of Kidney Diseases, Vol. XX, No. 2 (August) 1992: pp. 159-161; Gardiner, Can J. Gastroenterol, Vol. 11, No. 7 (October) 1997: pp. 573-577.)
Conventional therapies applied to patients with hyperpotassemia include calcium gluconate therapy, glucose-insulin therapy, sodium bicarbonate therapy, saline therapy or a combination thereof for relative emergency cases, or dialysis therapy and cation-exchange therapy based on administration of cation-exchange resin such as polystyrene sulfonate for non-emergency cases. Among these therapies, the cation-exchange therapy involving removing potassium from the body by replacement of potassium ions in intestinal tracts is generally conducted for patients with chronic renal insufficiency, and in this therapy, a daily dosage of 15 to 30 g polystyrene sulfonate for an adult person is divided into 2 to 3 portions and each portion is suspended in 30 to 50 ml water and orally administered. However, polystyrene sulfonate is a powder which is hardly dissolved in water and it should be taken in a large amount, so it feels strongly unpleasant in the oral cavity upon ingestion, and it is noted that there are many cases where compliance with clinician's instructions is not obeyed.
The polystyrene sulfonate when suspended in water is easily precipitated at the bottom of a cup, thus making it difficult to take the whole dose all at once, so some patients take powdery sulfonate polystyrene with water in the oral cavity without previously suspending it. In this case, there is a possibility that the polystyrene sulfonate is not uniformly dispersed in digestive tracts and forms agglomerates, thus failing to bring about the desired pharmaceutical effect. Further, the polystyrene sulfonate when taken in the form of powder feels strongly unpleasant in the oral cavity, to become a great mental burden on the patient. Hence, the polystyrene sulfonate gives a remarkably unpleasant feeling in the oral cavity, and according to the present application method, it is difficult to take the whole of a prescribed dose all at once, so under the present circumstances, the patient drinks a large amount of water to take it, which is contraindicated for renal insufficiency.
Recently, the method of administering the pharmaceutical preparation is recently devised in some hospitals, and it is reported that the improvement of compliance is attempted by manufacturing calcium polystyrene sulfonate etc. into jelly preparations {"Shinryo To Shinyaku", Vol. 29, No. 2, p. 514 (1992), "Shinryo To Shinyaku", Vol. 31, No. 11, p. 1911 (1994); and "Iyaku No Mon", Vol. 31, No. 3, p. 190 (1991)}.
A patent application KR20120013285A discloses preparation of the pharmaceutical composition of calcium polystyrene sulfonate in the form of a powder, a granule or a dry syrup.
Accordingly, development of a sorbitol-free sodium polystyrene sulfonate suspension which is physically and chemically stable for the treatment of hyperkalemia is desirable.
Therefore, it is necessary to develop an alternate formulation which can be overcome the problem of prior art.
The present invention provides a stable pharmaceutical composition in form of suspension of calcium polystyrene sulfonate comprising a calcium polystyrene sulfonate and other suitable pharmaceutically acceptable excipients for the treatment of Hyperkalemia.
The inventors of the present invention surprisingly found that the stable oral suspension of calcium polystyrene sulfonate which overcoming the problem of prior art.

EMBODIMENTS OF THE INVENTION
The main objective of the invention is to provide a stable pharmaceutical composition of calcium polystyrene sulfonate in form of suspension.
In embodiment, the main objective of the present invention is to provide stable oral suspension which comprising
(a) Calcium polystyrene sulfonate
(b) Suitable suspending agents;
(c) Suitable solvents selected from water, propylene glycol, glycerin, polyethylene glycol or combination thereof;
(d) Optionally other suitable pharmaceutically acceptable excipients.
The calcium polystyrene sulfonate used in preparation of suspension of the present invention is having particle size less than 150 µm.
Another objective of the invention is to provide a process for the preparation of the stable oral suspension of calcium polystyrene sulfonate.
In a further embodiment, the stable oral suspension of calcium polystyrene sulfonate is use for the treatment of Hyperkalemia.
In embodiment, the present invention is also provide a stable oral suspension which comprises:
(a) Sodium polystyrene sulfonate
(b) Suitable suspending agents;
(c) Suitable solvents selected from water, propylene glycol, glycerin, polyethylene glycol or combination thereof;
(d) Optionally other suitable pharmaceutically acceptable excipients.
The sodium polystyrene sulfonate used in preparation of suspension of the present invention is having particle size less than 150 µm.
Another objective of the invention is to provide a process for the preparation of the stable oral suspension of sodium polystyrene sulfonate.
In a further embodiment, the stable oral suspension of sodium polystyrene sulfonate is use for the treatment of Hyperkalemia.
DETAILED DESCRIPTION OF THE INVENTION
The main objective of the invention is to provide a stable pharmaceutical composition of calcium polystyrene sulfonate in form of suspension.
The calcium polystyrene sulfonate exists as a cation exchange resin and is typically administered as an oral solution or in an enema. As the resin passes along the intestine after oral administration or is retained in the colon by rectal administration, the calcium ions are partially released and replaced by potassium ions. For the most part, this action occurs in the large intestine, which excretes potassium ions to a greater extent than does the small intestine.
In an embodiment, the main objective of the present invention is to provide stable oral suspension which comprising;
(a) Calcium polystyrene sulfonate
(b) Suitable suspending agent(s);
(c) Suitable solvents selected from water, propylene glycol, glycerin, polyethylene glycol or suitable combination thereof;
(d) Optionally other suitable pharmaceutically acceptable excipients.
The calcium polystyrene sulfonate used in preparation of suspension of the present invention is having particle size less than 150 µm.
A stable oral suspension of calcium polystyrene sulfonate has a calcium concentration in the range of 1.0 g to 15.0 g per 60.0 mL.
The average total daily dosage of calcium polystyrene sulfonate is 15 g to 60 g, which is administered as a 15 g dose. The dose given daily is one to four time.
The suspending agent(s) used can be selected from carbomers, polyvinyl alcohol, polyvinyl pyrrolidone, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, magnesium aluminum silicate, aluminum hydroxide. hydroxypropyl cellulose, methyl cellulose, carboxymethyl cellulose, microcrystalline cellulose, powdered cellulose, xanthan gum, gellan gum, carageenan, acacia, tragacanth, gelatin, guar gum, alginic acid, sodium alginates, propylene glycol alginate, methacrylic acid and methyl methacrylate copolymer, dextrin, dextran, dextran-polyethylene glycol conjugates, and the glycosaminoglycans and/or mixtures thereof.
The concentration of suspending agents used in a stable oral suspension is in the range of 0.3 g to 0.9 g in total weight of suspension.
The concentration of suspending agents used in a stable oral suspension is in the range of 0.3 g to 0.4 g in total weight of suspension.
The concentration of suspending agents used in a stable oral suspension is in the range of 0.4 g to 0.5 g in total weight of suspension.
The concentration of suspending agents used in a stable oral suspension is in the range of 0.5 g to 0.6 g in total weight of suspension.
The concentration of suspending agents used in a stable oral suspension is in the range of 0.6 g to 0.7 g in total weight of suspension.
The concentration of suspending agents used in a stable oral suspension is in the range of 0.7 g to 0.8 g in total weight of suspension.
The concentration of suspending agents used in a stable oral suspension is in the range of 0.8 g to 0.9 g in total weight of suspension.
Optionally other pharmaceutically acceptable excipients used for the preparation of oral stable suspension are selected from preservatives, sweetening agents, buffers and flavoring agents.
The preservatives used can be selected from methyl paraben, propyl paraben, phenol, benzoic acid, boric acid, chloro-cresol, 9-phenyl phenol, alkyl esters of para-hydroxybenzoic acid, sorbic acid, and their respective salts, chlorobutanol, benzyl alcohol, and beta-phenylethyl alcohol, sodium benzoate and/or mixtures thereof.
The sweetening agents used can be selected from acesulfame K, alitame, aspartame, dextrose, fructose, galactose, inulin, isomalt, lactitol, maltitol, maltose, mannitol, neohesperidin, dihydrochalcone, saccharin sodium, cyclamate, sorbitol, sucralose, sucrose, tagatose, thaumatin, treehouse, xylitol and/or mixtures thereof.
The buffers/pH adjusters used can be selected from citric acid monohydrate, carbonates, tartrate, citrate, and various phosphate salts and/or mixtures thereof.
The flavoring agents used can be selected from mango, apple, orange banana, grape, cinnamon, berries, chocolate, pineapple, clove, rose, vanillin and/or mixtures thereof.
In a preferred embodiment, present invention discloses a stable oral suspension comprising 15 g calcium polystyrene sulfonate, 0.42 g magnesium aluminum silicate, 2.4 g propylene glycol, 0.12 g xanthan gum, 0.108 g methyl paraben, 0.012 g propyl paraben, 0.12 g citric acid monohydrate, 0.3 g sodium saccharin and 0.3 g pineapple flavour.
A stable oral suspension prepared as per the present invention is fill in the aluminium pouch with cap
In a further embodiment, present invention also provides a process of preparing of a stable oral suspension of calcium polystyrene sulfonate comprises the step of:
1. Suitable first suspending agent in water at suitable temperature with continuous stirring.
2. Suitable second suspending agent in suitable solvent added to step-1 at suitable temperature with continuous stirring.
3. Suitable preservative in suitable solvent added to step-1 at suitable temperature with continuous stirring.
4. Add calcium polystyrene sulfonate in step-1 at suitable temperature with continuous stirring.
5. Dissolve sweetening agent in purified water and add it to step-1 solution with continuous stirring.
6. Dissolve buffer in purified water and add it to step-1 solution with continuous stirring.
7. Add flavouring agent to step-1 under stirring.
8. Make up the volume with boiled and cooled purified water and homogenize the suspension for appropriate time.
9. Fill the solution in 60 ml of Aluminium pouch with cap.
Order of the step of above mentioned process may vary as per the requirement.
In a further embodiment, the stable oral suspension of calcium polystyrene sulfonate is useful for the treatment of Hyperkalemia.
In embodiment, the main objective of the present invention is to provide stable oral suspension which comprising;
(a) Sodium polystyrene sulfonate
(b) Suitable suspending agent(s);
(c) Suitable solvents selected from water, propylene glycol, glycerin, polyethylene glycol or suitable combination thereof;
(d) Optionally other suitable pharmaceutically acceptable excipients.
The sodium polystyrene sulfonate used in preparation of suspension of the present invention is having particle size less than 150 µm.
A pharmaceutical composition of sodium polystyrene sulfonate has a calcium concentration in the range of 1.0 g to 15.0 g per 60.0 mL.
The average total daily dosage of sodium polystyrene sulfonate is 15 g to 60 g, which is administered as a 15 g dose. The dose given daily is one to four time.
The suspending agent(s) used can be selected from carbomers, polyvinyl alcohol, polyvinyl pyrrolidone, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, magnesium aluminum silicate, aluminum hydroxide. hydroxypropyl cellulose, methyl cellulose, carboxymethyl cellulose, microcrystalline cellulose, powdered cellulose, xanthan gum, gellan gum, carageenan, acacia, tragacanth, gelatin, guar gum, alginic acid, sodium alginates, propylene glycol alginate, methacrylic acid and methyl methacrylate copolymer, dextrin, dextran, dextran-polyethylene glycol conjugates, and the glycosaminoglycans and/or mixtures thereof.
The concentration of suspending agents used in a stable oral suspension is in the range of 0.3 g to 0.9 g in total weight of suspension.
The concentration of suspending agents used in a stable oral suspension is in the range of 0.3 g to 0.4 g in total weight of suspension.
The concentration of suspending agents used in a stable oral suspension is in the range of 0.4 g to 0.5 g in total weight of suspension.
The concentration of suspending agents used in a stable oral suspension is in the range of 0.5 g to 0.6 g in total weight of suspension.
The concentration of suspending agents used in a stable oral suspension is in the range of 0.6 g to 0.7 g in total weight of suspension.
The concentration of suspending agents used in a stable oral suspension is in the range of 0.7 g to 0.8 g in total weight of suspension.
The concentration of suspending agents used in a stable oral suspension is in the range of 0.8 g to 0.9 g in total weight of suspension.
Optionally other pharmaceutically acceptable excipients used for the preparation of oral stable suspension are selected from preservatives, sweetening agents, buffers and flavoring agents.
The preservatives used can be selected from methyl paraben, propyl paraben, phenol, benzoic acid, boric acid, chloro-cresol, 9-phenyl phenol, alkyl esters of para-hydroxybenzoic acid, sorbic acid, and their respective salts, chlorobutanol, benzyl alcohol, and beta-phenylethyl alcohol, sodium benzoate and/or mixtures thereof.
The sweetening agents used can be selected from acesulfame K, alitame, aspartame, dextrose, fructose, galactose, inulin, isomalt, lactitol, maltitol, maltose, mannitol, neohesperidin, dihydrochalcone, saccharin sodium, cyclamate, sorbitol, sucralose, sucrose, tagatose, thaumatin, treehouse, xylitol and/or mixtures thereof.
The buffers/pH adjusters used can be selected from citric acid monohydrate, carbonates, tartrate, citrate, and various phosphate salts and/or mixtures thereof.
The flavoring agents used can be selected from mango, apple, orange banana, grape, cinnamon, berries, chocolate, pineapple, clove, rose, vanillin and/or mixtures thereof.
In a further embodiment, present invention also provides a process of preparing of a stable oral suspension of sodium polystyrene sulfonate comprises the step of:
1. Suitable first suspending agent in water at suitable temperature with continuous stirring.
2. Suitable second suspending agent in suitable solvent added to step-1 at suitable temperature with continuous stirring.
3. Suitable preservative in suitable solvent added to step-1 at suitable temperature with continuous stirring.
4. Add sodium polystyrene sulfonate in step-1 at suitable temperature with continuous stirring.
5. Dissolve sweetening agent in purified water and add it to step-1 solution with continuous stirring.
6. Dissolve buffer in purified water and add it to step-1 solution with continuous stirring.
7. Add flavouring agent to step-1 under stirring.
8. Make up the volume with boiled and cooled purified water and homogenize the suspension for appropriate time.
9. Fill the solution in 60 ml of Aluminium pouch with cap.
Order of the step of above mentioned process may vary as per the requirement.
In a further embodiment, the stable oral suspension of sodium polystyrene sulfonate is useful for the treatment of Hyperkalemia.
The invention is further exemplified by the following non-limiting examples, which are illustrative representing the preferred modes of carrying out the invention. The invention’s scope is not limited to these specific embodiments only but should be read in conjunction with what is disclosed anywhere else in the specification together with those information and knowledge that are within the general understanding of a person skilled in the art.
Example 1:
Table 1: Manufacturing Formula of example 1

Sr. No. Ingredients Quantity
g / 60 ml %w/v
1 Calcium polystyrene sulphonate 15.000 25.00
2 Magnesium aluminum silicate 0.420 0.70
3 Propylene glycol 2.400 4.00
4 Xanthan gum 0.120 0.20
5 Methyl paraben 0.108 0.18
6 Propyl paraben 0.012 0.02
7 Citric acid monohydrate 0.120 0.20
8 Sodium saccharin 0.300 0.50
9 Pineapple flavour 0.300 0.50
10 Purified water q.s to 60 ml q.s to 100%
Total 60 ml 100.00

Brief Manufacturing Process of Example 1:
1. Take boiled and cooled purified water in main manufacturing SS vessel and heat up to 60°C-70°C and slowly add magnesium aluminum silicate with continuous stirring till lump free off-white dispersion is obtained.
2. Disperse xanthan gum in propylene glycol in SS vessel under stirring till lump free dispersion is obtained. Then add it to step-1 with continuous stirring at 60°C-70°C temperature till off-white viscous lump free dispersion is obtained.
3. Take propylene glycol in SS vessel heat to 60°C-70°C then dissolve dispensed quantity of methyl paraben and propyl paraben under stirring, add propylene glycol after rinsing the preservative bags. (Mixing time: till completely dissolve) Then add it to step-1 with continuous stirring at 50°C-60°C temperature till off-white viscous lump free dispersion. Then cool the dispersion to room temerature.
4. Add calcium polystyrene sulfonate in step-1 below 35 °C under stirring till uniform dispersion obtained without lumps.
5. Dissolve sodium saccharin in purified water and add it to step-1 solution with continuous stirring.
6. Dissolve citric acid monohydrate in purified water and added to step-1 solution with continuous stirring.
7. Add flavour pineapple to step-1 under stirring.
8. Make up the volume with boiled and cooled purified water and homogenize the suspension for appropriate time.
9. Fill the solution in 60 ml of aluminium pouch with cap.
Table 2: Finish product results of example 1

Sr. No. Test Specifications of finish product Results
1. Description Light brown to brown viscous suspension with characteristics odour in which small white particulates may remain visible, filled in spouted aluminium base laminated pouch with cap. Light brown viscous suspension with characteristics odour filled in aluminium base laminated pouch with cap.
2. Calcium content 6.5% to 9.5% of labelled amount 8.72
3. Methyl paraben 90.0% to 110.0% of labelled amount 107.1
4. Propyl paraben 90.0% to 110.0% of labelled amount 107.5
5. pH 2.5 to 7.0 3.39
6. Potassium exchange capacity 1.3 mEq to 2.0 mEq 1.8537 (In-vivo or in-vitro)
7. Microbial enumeration test
Total Aerobic Count (TAC)
Total Fungal Count (TFC)
Escherichia Coli

NMT 200 CFU/ml

NMT 20 CFU/ml

Should be absent in 1 ml Complies with the specification

Table 3: Stability data of example 1 at 40°C/75%RH
Condition: 40°C/75%RH
Tests Specification Time (months)
Initial 1 2 3 6
Description Light brown to brown colour viscous suspension with characteristics odour in which small white particulates may remain visible filled in aluminium base laminated pouch with cap. Complies with the specification Complies with the specification Complies with the specification Complies with the specification Complies with the specification
pH 2.5 to 7.0 3.39 4.54 4.81 4.82 5.00
Potassium exchange capacity 1.3 to 2.0 mEq/g 1.8537 mEq/g 1.7352 mEq/g 1.6731 mEq/g 1.7814 mEq/g 1.5331 mEq/g
Assay 6.5% to 9.5% of stated amount of Calcium 8.72% 8.90% 8.94% 8.84% 8.22%
NLT 50.0%
(Methyl Paraben IP) 107.1% 100.8% 103.0% 102.0% 93.5%
NLT 50.0%
(Propyl Paraben IP) 107.5% 95.8% 99.0% 97.2% 87.2%
Microbial limit Test Total Aerobic Count (TAC) = NMT 100 CFU/g
Total Fungi Count (TFC) = NMT 10 CFU/g
E. Coli = Should be absent/g Complies with the specification NA NA NA Complies with the specification

Table 4: Stability data of example 1 at 30°C/75%RH

Condition: 30°C/75%RH
Tests Specification Time (months)
Initial 1 2 3 6 24
Description Light brown to brown colour viscous suspension with characteristics odour in which small white particulates may remain visible filled in aluminium base laminated pouch with cap. Complies with the specification Complies with the specification Complies with the specification Complies with the specification Complies with the specification Complies with the specification
pH 2.5 to 7.0 3.39 4.78 5.00 4.88 4.92 5.10
Potassium Exchange Capacity 1.3 to 2.0 mEq/g 1.8537 mEq/g 1.7887 mEq/g 1.5245 mEq/g 1.8494 mEq/gm Not applicable 1.464 mEq/g
Assay 6.5% to 9.5% of stated amount of Calcium 8.72% 8.74% 8.21% 8.12% 8.08% 8.09%
NLT 50.0%
(Methyl Paraben IP) 107.1% 99.1% 97.2% 100.4% 95.3% 92.6%
NLT 50.0%
(Propyl Paraben IP) 107.5% 93.6% 91.7% 95.9% 93.1% 86.8%
Microbial Limit Test Total Aerobic Count (TAC) = NMT 100 CFU/g,
Total Fungi Count (TFC) = NMT 10 CFU/g,
E Coli = Should be absent/g Complies with the specification NA NA NA NA Complies with the specification

Example 2:
Table 5: Manufacturing formula of example 2

Sr. No. Ingredients Quantity
Gm /60 ml %w/v
1 Calcium Polystyrene Sulphonate 15.000 25.00
2 Magnesium Aluminum Silicate 0.230 0.38
3 Propylene Glycol 2.400 4.00
4 Xanthan Gum 0.070 0.12
5 Methyl Paraben 0.108 0.18
6 Propyl Paraben 0.012 0.02
7 Citric Acid Monohydrate 0.120 0.20
8 Sodium Saccharin 0.300 0.50
9 Pineapple Flavour 0.300 0.50
10 Purified Water q.s to 60 ml q.s to 100%
Total 60 ml 100.00

Brief Manufacturing Process of example 2: As per the process given in Example 1.

Example 3:
Table 6: Manufacturing formula of example 3

Sr. No. Ingredients Quantity
Gm /60 ml %w/v
1 Calcium Polystyrene Sulphonate 15.000 25.00
2 Magnesium Aluminum Silicate 0.450 0.75
3 Propylene Glycol 2.400 4.00
4 Xanthan Gum 0.150 0.25
5 Methyl Paraben 0.108 0.18
6 Propyl Paraben 0.012 0.02
7 Citric Acid Monohydrate 0.120 0.20
8 Sodium Saccharin 0.300 0.50
9 Pineapple Flavour 0.300 0.50
10 Purified Water q.s to 60 ml q.s to 100%
Total 60 ml 100.00

Brief Manufacturing Process of example 3: As per the process given in Example 1.

Example 4:
Table 7: Manufacturing formula of example 4

Sr. No. Ingredients Quantity
Gm /60 ml %w/v
1 Calcium Polystyrene Sulphonate 15.000 25.00
2 Magnesium Aluminum Silicate 0.700 1.17
3 Propylene Glycol 2.400 4.00
4 Xanthan Gum 0.200 0.33
5 Methyl Paraben 0.108 0.18
6 Propyl Paraben 0.012 0.02
7 Citric Acid Monohydrate 0.120 0.20
8 Sodium Saccharin 0.300 0.50
9 Pineapple Flavour 0.300 0.50
10 Purified Water q.s to 60 ml q.s to 100%
Total 60 ml 100.00

Brief Manufacturing Process of example 4: As per the process given in Example 1.

Example 5:
Table 8: Manufacturing formula of example 5

Sr. No. Ingredients Quantity
g / 60 ml %w/v
1 Calcium polystyrene sulphonate 15.000 25.00
2 Magnesium aluminum silicate 0.420 0.70
3 Propylene glycol 2.400 4.00
4 Xanthan gum 0.120 0.20
5 Methyl paraben 0.108 0.18
6 Propyl paraben 0.012 0.02
7 Sodium benzoate 0.420 0.70
8 Sodium saccharin 0.300 0.50
9 Pineapple flavour 0.300 0.50
10 Purified water q.s to 60 ml q.s to 100%
Total 60 ml 100.00

Brief Manufacturing Process of example 5:

1. Magnesium aluminum silicate was dispersed in 60°C-70°C purified water with continuous stirring till lump free off-white dispersion is obtained.
2. Disperse xanthan gum in propylene glycol in SS vessel under stirring till lump free dispersion is obtained. Then add it to step-1 with continuous stirring at 60°C-70°C temperature till off-white viscous lump free dispersion is obtained.
3. Take propylene glycol in SS vessel heat to 60°C-70°C then dissolve dispensed quantity of methyl paraben and propyl paraben under stirring, add propylene glycol after rinsing the preservative bags. (Mixing time: till completely dissolve) Then add it to step-1 with continuous stirring at 50°C-60°C temperature till off-white viscous lump free dispersion is obtained. Then cool the dispersion to room temperature.
4. Dissolve sodium benzoate in purified water and then add it to step-1 dispersion.
5. Add calcium polystyrene sulfonate in step-1 below 35°C under stirring till uniform dispersion obtained without lumps.
6. Dissolve sodium saccharin in purified water and add it to step-1 solution with continuous stirring.
7. Add flavour pineapple to step-1 under stirring.
8. Make up the volume with boiled and cooled purified water and homogenize the suspension for appropriate time.
9. Fill the solution in 60 ml of aluminium pouch with cap.

,CLAIMS:We claim:
1. A stable oral suspension comprising:
(a) Calcium polystyrene sulfonate
(b) Suitable suspending agent(s);
(c) Suitable solvents selected from water, propylene glycol, glycerin, polyethylene glycol or suitable combination thereof;
(d) Optionally other suitable pharmaceutically acceptable excipients.

2. A stable oral suspension as claimed in claim 1 wherein calcium polystyrene sulfonate having particle size less than 150 µm.
3. A stable oral suspension as claimed in claim 1 wherein calcium concentration is in the range of 1.0 g to 15.0 g per 60.0 mL.
4. A stable oral suspension as claimed in claim 1 wherein the suspending agent(s) are selected from carbomers, polyvinyl alcohol, polyvinyl pyrrolidone, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, magnesium aluminum silicate, aluminum hydroxide. hydroxypropyl cellulose, methyl cellulose, carboxymethyl cellulose, microcrystalline cellulose, powdered cellulose, xanthan gum, gellan gum, carageenan, acacia, tragacanth, gelatin, guar gum, alginic acid, sodium alginates, propylene glycol alginate, methacrylic acid and methyl methacrylate copolymer, dextrin, dextran, dextran-polyethylene glycol conjugates, and the glycosaminoglycans and/or mixtures thereof.
5. A stable oral suspension as claimed in claim 1 wherein concentration of suspending agent is in the range of 0.3 g to 0.9 g in total weight of suspension.
6. A stable oral suspension as claimed in claim 1 wherein concentration of suspending agent is in the range of 0.3 g to 0.4 g in total weight of suspension.
7. A stable oral suspension as claimed in claim 1 wherein concentration of suspending agent is in the range of 0.4 g to 0.5 g in total weight of suspension.
8. A stable oral suspension as claimed in claim 1 wherein concentration of suspending agent is in the range of 0.5 g to 0.6 g in total weight of suspension.
9. A stable oral suspension as claimed in claim 1 wherein concentration of suspending agent is in the range of 0.6 g to 0.7 g in total weight of suspension.
10. A stable oral suspension as claimed in claim 1 wherein concentration of suspending agent is in the range of 0.7 g to 0.8 g in total weight of suspension.
11. A stable oral suspension as claimed in claim 1 wherein concentration of suspending agent is in the range of 0.8 g to 0.9 g in total weight of suspension.
12. A stable oral suspension as claimed in claim 1 wherein other suitable pharmaceutically acceptable excipients are selected from preservatives, sweetening agents, buffers and flavoring agents.
13. A stable oral suspension as claimed in claim 12 wherein preservatives are selected from methyl paraben, propyl paraben, phenol, benzoic acid, boric acid, chloro-cresol, 9-phenyl phenol, alkyl esters of para-hydroxybenzoic acid, sorbic acid, and their respective salts, chlorobutanol, benzyl alcohol, and beta-phenylethyl alcohol, sodium benzoate and/or mixtures thereof.
14. A stable oral suspension as claimed in claim 12 wherein sweetening agents are selected from acesulfame K, alitame, aspartame, dextrose, fructose, galactose, inulin, isomalt, lactitol, maltitol, maltose, mannitol, neohesperidin, dihydrochalcone, saccharin sodium, cyclamate, sorbitol, sucralose, sucrose, tagatose, thaumatin, treehouse, xylitol and/or mixtures thereof.
15. A stable oral suspension as claimed in claim 12 wherein buffers selected from citric acid, carbonates, tartrate, citrate, and various phosphate salts and/or mixtures thereof.
16. A stable oral suspension as claimed in claim 12 wherein flavoring agents are selected from mango, apple, orange banana, grape, cinnamon, berries, chocolate, pineapple, clove, rose, vanillin and/or mixtures thereof.
17. A process for preparing a stable oral suspension of calcium polystyrene sulfonate as claimed in claim comprises the step of:
(i) Suitable first suspending agent in water at suitable temperature with continuous stirring.
(ii) Suitable second suspending agent in suitable solvent added to step-1 at suitable temperature with continuous stirring.
(iii) Suitable preservative in suitable solvent added to step-1 at suitable temperature with continuous stirring.
(iv) Add calcium polystyrene sulfonate in step-1 at suitable temperature with continuous stirring.
(v) Dissolve sweetening agent in purified water and add it to step-1 solution with continuous stirring.
(vi) Dissolve buffer in purified water and add it to step-1 solution with continuous stirring.
(vii) Add flavouring agent to step-1 under stirring.
(viii) Make up the volume with boiled and cooled purified water and homogenize the suspension for appropriate time.
(ix) Fill the solution in 60 ml of aluminium pouch with cap.

18. A stable oral suspension comprising 15 g calcium polystyrene sulfonate, 0.42 g magnesium aluminum silicate, 2.4 g propylene glycol, 0.12 g xanthan gum, 0.108 g methyl paraben, 0.012 g propyl paraben, 0.12 g citric acid monohydrate, 0.3 g sodium saccharin and 0.3 g pineapple flavour.
19. A stable oral suspension as claimed in claim 18 is fill in the aluminium pouch with cap.
20. A stable oral suspension as claimed in claim 1 is useful for the treatment of Hyperkalemia.

Dated this 29th day of December 2023.

(HARIHARAN SUBRAMANIAM)
IN/PA-93
Of SUBRAMANIAM & ASSOCIATES
ATTORNEYS FOR THE APPLICANTS