A suspension for solution of potassium and magnesium salts and a method of preparation thereof

Abstract

The present invention discloses a suspension for solution formulation of high concentrations of potassium and magnesium salts for patients The formulation 5 includes potassium chloride 15 to 95 w / v%, magnesium chloride 0.5 to 95 w / v%, first polysaccharide gum 0.05 to 3 w / v%, second polysaccharide gum 0.01 to 3 w / v%, preservative 0.001 to 10 w / v%, colour 0.0001 to 10 w / v%, essence 0.001 to 10 v / v%, and demineralised purified water 1 to 99 v / v%. Further, it discloses a method of preparation of the same. The method involves preparing a suspension for 10 solution formulation of potassium and magnesium salts for patients, including prerequisite steps and final preparation steps. The formulation delivers high concentrations of freely soluble salts to meet daily salt requirements for patients without compromising stability or patient safety.

Description

[0001]“A SUSPENSION FOR SOLUTION OF POTASSIUM AND MAGNESIUM SALTS AND A METHOD OF PREPARATION THEREOF” FIELD OF THE INVENTION: The present invention relates to a suspension for solution formulation of potassium and magnesium salts, more particularly to a suspension for solution formulation of high concentrations of potassium and magnesium salts. The present invention further relates to a method of preparation of the suspension for solution formulation of potassium and magnesium salts. BACKGROUND OF THE INVENTION: Mineral nutrition significantly impacts animal performance, particularly in large animal segments like horses and cattle, where it is capable of affecting appetite, milk production, and fertility and may lead to deficiencies in their performance. The seven macro minerals that matter most in their diet include: potassium (K), phosphorus (P), calcium (Ca), magnesium (Mg), sulfur (S), sodium (Na) and chlorine (Cl). Among all, potassium is the third most abundant mineral in the body. It is important for acid-base balance, regulating osmotic pressure and water balance, contracting muscles, nerve impulses and even for certain enzyme reactions. Hypokalemia and hyperkalemia are common electrolyte disorders caused by changes in potassium intake, altered excretion, or transcellular shifts. Hypokalaemic animals show depression, muscle weakness, and difficulty standing or raising their heads. Similarly, magnesium is crucial for energy metabolism, DNA transmission, membrane transportation, and nerve impulse transmission. Cattles may sometimes show signs of magnesium deficiency, including excitability, anorexia, convulsions, and twitching. Magnesium deficiency is frequently associated with hypokalemia. Concomitant magnesium deficiency aggravates hypokalemia and renders it refractory to treatment by potassium. In general, cattle require 60 - 120 g of potassium and 20 - 30 g of magnesium daily. Therefore, supplements are usually needed for effective supplementation of KCl and MgCl2. But no direct combination of salts is available. Further, in general, potassium and magnesium deficiencies are treated with separate medications. KCl and MgCl2are soluble salts that are often used in oral medication solutions, but this method restricts dosages based on solubility in water, causing crystallization or phase separation. Further, to deliver high doses in solution, large packing / bottle sizes are required for high dose delivery, potentially causing transportation issues, affecting customer comfort, and being impractical and less economical. Furthermore, salts are easily formulated into tablets or capsules, but have limitations as they have low gastrointestinal tolerance and may cause stomach irritation and vomiting. Also, as tablets and capsules are unit dosage forms, there is minimal flexibility for a patient to adjust the dosage. The article “Efficacy of oral potassium chloride administration in treating lactating dairy cows with experimentally induced hypokalemia, hypochloremia, and alkalemia” by Peter D Constable and others in the Journal of Dairy Science discloses a study that investigated the safety and effectiveness of a 24-hour oral potassium chloride dose of 0.4 g / kg BW in hypokalaemic cattle, the optimal dosage, and the impact of oral KCl administration on magnesium concentration and excretion. The study suggested that hypokalaemic calves may need multiple doses of KCl oral formulations, while inappetent lactating dairy cattle may need additional magnesium to minimise magnesium -induced potassium deficiency. The U.S. patent application US20140057022A1 to Hoejvang-Nielsen Leif discloses a potassium-containing preparation or bolus for preventing or treating potassium deficit in ruminants. It provides a potassium content of up to 70% by adding calcium chloride and water to the potassium salt. However, potassium boluses manage electrolyte imbalances in cattle and ruminants, but they may cause gastrointestinal irritation, hyperkalemia, and interfere with other electrolytes, leading to muscle weakness and reduced feed intake. Therefore, there is a need for a formulation that safely and economically delivers high concentrations of readily soluble salts like potassium chloride and magnesium chloride to patients. There is also a need for a method that produces a stable and palatable formulation of the same. SUMMARY OF THE INVENTION: The present invention discloses a suspension for solution formulation of potassium and magnesium salts and a method of preparation of the suspension for solution formulation of potassium and magnesium salts. The suspension for the solution formulation of potassium and magnesium salts includes 15 to 95 w / v% of potassium chloride, 0.5 to 95 w / v% of magnesium chloride, 0.05 to 3 w / v% of a first polysaccharide gum that is xanthan gum, 0.01 to 3 w / v% of a second polysaccharide gum that is guar gum, 0.001 to 10 w / v% of a preservative selected from sodium benzoate or benzoic acid, 0.0001 to 10 w / v% of colour, 0.0001 to 10 w / v% of essence and a sufficient quantity of demineralised purified water. Further, the suspension has a Brookfield viscosity of 150–800 cP, remains free of visible crystallization and phase separation during storage, and forms a clear solution when diluted at a ratio of ≥1:4 (v / v) with potable water. Further, the preservative is selected from benzoic acid, sodium benzoate and the like; the colour is selected from sunset yellow FCF I.H. and the like, synthetic dyes is selected from categories azos, nitros, nitrosos, trimethylmethane, phthaleins, indigos, anthraquinones, and the like; and the essence is selected from raspberry I.H., citrous, fruity, and milky flavours and the like. Additionally, the formulation further includes polysorbates, individually or as a mixture, at a concentration of 0.05–2% w / v to enhance wetting. In accordance with the present invention, 100% of potassium chloride particles is pass through a 40-mesh sieve (<420 µm) and have a particle size distribution characterized by D10 ≥ 50 µm, D50 between 100 and 250 µm, and D90 ≤ 400 µm. Additionally, the formulation is filled into containers made from thermoplastic polymer selected from high-density polyethylene (HDPE), polypropylene (PP), polyethylene terephthalate (PET) or the like. The contact surfaces of the processing equipment are constructed from 316L stainless steel to prevent corrosion and contamination. In another embodiment of the present invention, a method of preparation of the suspension for solution formulation of potassium and magnesium salts is described. The method includes a first phase of a series of prerequisite steps carried out before the preparation of the suspension for solution formulation of potassium and magnesium salts; and a second phase of a series of steps carried out for the final preparation of the suspension for solution formulation of potassium and magnesium salts. In the first phase, the steps included a first step of dissolving magnesium chloride, a second step of dissolving preservative with gums, and a third step of dissolving colour. In the first step, 0.5 to 40 w / v% of magnesium chloride is dissolved in demineralised purified water (DMPW) at room temperature. In the second step, 0.001 to 10 w / v% of preservative selected from sodium benzoate, benzoic acid and the like is dissolved in demineralised purified water (DMPW) at 0 to 150°C, and to this, 0.05 to 3 w / v% of xanthan gum and 0.01% to 3 w / v% of guar gum are added, followed by stirring and homogenization at a speed of 1 to 5000 RPM, and followed by soaking for 0.01 to 168 hours. In the third step, 0.0001 to 10 w / v% of colour is dissolved in demineralised purified water (DMPW) at 0 to 150°C. In the second phase, the steps included a first step of pulverising potassium chloride, a second step of slurry formation, a third step of addition of magnesium chloride solution, a fourth step of addition of a mixture of preservative and gum, a fifth step of addition of colour and flavour, and a sixth step of making up the final volume. In the first step of the second phase, 15 – 95 w / v % of potassium chloride is pulverised using a mill having non-erosive contact surfaces made up of quality SS 316 L to obtain potassium chloride of resultant particle size less than 40 mesh of the American Standard Test Sieve Series [ASTM]. In the second step, the pulverised potassium chloride obtained in the first step is mixed into demineralised purified water (DMPW) at the speed of 1 - 5000 RPM with continuous stirring to get a uniform slurry. In the third step of the second phase, magnesium chloride solution prepared in the first step is added to the slurry of the second step at 1 - 5000 RPM at a high speed with continuous stirring to get a uniform slurry. In the fourth step, the mixture of preservative selected from sodium benzoate, benzoic acid and the like and gum prepared in the second step is added at a high speed of 1 - 5000 RPM with continuous stirring to get a suspension. In the fifth step of the second phase, the colour solution prepared in the third step is added to the slurry of the fourth step along with 0.001 to 10 w / v% of flavour or essence at a high speed of 1 - 5000 RPM with continuous stirring to get a uniform coloured and flavoured suspension. In the sixth step, the final volume of the suspension is made up at 1-5000 RPM to get a final uniform suspension for solution formulation of potassium and magnesium salts. BRIEF DESCRIPTION OF DRAWINGS: The objectives and advantages of the present invention will become apparent from the following description read in accordance with the accompanying drawings wherein, FIG.1 shows a theoretical illustrative representation of the finished formulation of suspension for solution having mesh of xanthan gum and guar gum with suspended potassium chloride particles in accordance with the present invention; and FIG.2 shows dilution directions for final solution preparation before administration for usage in accordance with the present invention. DESCRIPTION OF THE INVENTION: References in the specification to "one embodiment" or "an embodiment" means that a particular feature, structure, characteristic, or function described in connection with the embodiment is included in at least one embodiment of the invention. The appearances of the phrase “in one embodiment” in various places in the specification are not necessarily all referring to the same embodiment. References in the specification to “preferred embodiment” means that a particular feature, structure, characteristic, or function described in detail thereby omitting known constructions and functions for clear description of the present invention. The foregoing description of specific embodiments of the present invention has been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the present invention to the precise forms disclosed and obviously many modifications and variations are possible in light of the above teaching. The present invention relates to a unique formulation of suspension for a solution of high concentrations of potassium and magnesium salts for patients. As the measured dose of suspension disperses instantaneously in water before use, the formulation of the present invention is known as the suspension for solution formulation of potassium chloride and magnesium chloride. This results in a clear liquid solution. The present invention also relates to a method of preparation of the suspension for solution formulation of potassium and magnesium salts. Further, the suspension for solution formulation of the present invention enables delivery of high concentrations of freely soluble salts, including potassium chloride and magnesium chloride to patients. Furthermore, the formulation is efficiently absorbed by the body without issues related to solubility that could affect dosing or treatment outcomes. Moreover, the formulation of the present invention ensures that instability or improper salt concentrations does not have any negative impacts on its stability or on the patient's safety. Additionally, unlike supersaturated solutions, the resulting suspension for solution formulation is stable, does not form any crystals, and does not cause phase separation between 5°C and 60°C, ensuring that the formulation remains safe and effective for a wide range of temperatures. In one aspect, the present invention discloses a suspension for solution formulation of potassium and magnesium salts. In another aspect, the present invention describes a method of preparation of suspension for solution formulation of potassium and magnesium salts. In accordance with a preferred embodiment, the suspension for solution formulation of potassium and magnesium salts of the present invention includes the following ingredients a. potassium chloride b. magnesium chloride - 0.5 to 95 c. first polysaccharide gum - 0.05 to 3 d. second polysaccharide gum - 0.01 to e. preservative - 0.001 f. colour - 0.0001 to 10 w / v%, g. essence - 0.001 to 10 v / v%, and h. demineralised purified water - 1 to 99 v / v%. In accordance with a preferred embodiment of the present invention, the suspension for solution formulation includes 80 w / v% potassium chloride, 10 w / v% magnesium chloride, 0.18 w / v% first polysaccharide gum, w / v% 0.09 second polysaccharide gum, 0.02 w / v% preservative, 0.006 w / v% colour, 0.4 v / v% essence, and 9.304 v / v% demineralized purified water. The formulation may additionally include polysorbates, individually or in combination, at concentrations ranging from 0.05 to 2% w / v to enhance wetting properties. Further, the first and second polysaccharides are selected from xanthan gum, guar gum and the like. The preservative is selected from benzoic acid, sodium benzoate and the like. The colour is selected from sunset yellow FCF I.H., synthetic dyes are selected from categories azos, nitros, nitrosos, trimethylmethane, phthaleins, indigos, anthraquinones, and the like. The essence is selected from raspberry I.H., citrous, fruity, and milky flavours and the like. Furthermore, the suspension has a Brookfield viscosity ranging from 150 to 800 cP, providing optimal rheological properties for processing and application. The formulation demonstrates long-term physical stability, with no detectable crystallization or phase separation during storage. Additionally, when diluted with potable water at a volume ratio of 1:4 or greater, the suspension forms a clear, homogeneous solution, indicating complete dissolution and the absence of colloidal or particulate matter. Now a preferred method 100 of preparation of the suspension for solution formulation of potassium and magnesium salts (herein after referred to as “method 100”) in accordance with the present invention is described. The method 100 of preparation of the suspension for solution formulation of potassium and magnesium salts includes a first phase 101 and a second phase 201. The first phase 101 includes a set of prerequisite steps carried out before the preparation of the suspension for solution formulation of potassium and magnesium salts. The second phase 201 includes steps carried out for the final preparation of the suspension for solution formulation of potassium and magnesium salts for patients. The first phase 101 includes the prerequisite steps for the preparation of the suspension for solution formulation. A first step 110 involves dissolving magnesium chloride in demineralised purified water (DMPW); a second step 120 involves dissolving preservative in demineralised purified water (DMPW) along with xanthan gum and guar gum to prepare a homogenised mixture; and a third step 130 involves dissolving colour in demineralised purified water (DMPW). In accordance with the method 100 of the present invention, the first phase 101 includes the following steps: a. a first step 110 of dissolving magnesium chloride, b. a second step 120 of dissolving a preservative with gums, and c. a third step 130 of dissolving colour. The first step 110 of dissolving magnesium chloride includes dissolving a predefined quantity of magnesium chloride in predefined demineralised purified water (DMPW) at a predefined temperature. The second step 120 of dissolving preservative with gums includes dissolving a predefined quantity of preservative in predefined demineralised purified water (DMPW) at a predefined temperature. The second step further includes adding a predefined quantity of xanthan gum and guar gum to it. The mixture is then stirred and homogenised at a predetermined speed, followed by soaking for a predefined duration. The third step 130 of dissolving colour includes dissolving a predefined quantity of colour in a predefined demineralised purified water (DMPW) at a predefined temperature. In accordance with the present invention, in the first phase 101, the water generated by techniques including reverse osmosis (RO), electro-deionization (EDI), and mixed beds is defined as demineralised purified water (DMPW). In the first step 110, the amount of magnesium chloride ranges from 0.5 to 40 w / v% range, and the predefined temperature is room temperature. In the second step 120, the amount of preservative selected from benzoic acid, sodium benzoate and the like ranges from 0.001 to 10 w / v% range, and the predefined temperature range is 0 to 150oC. Further, 0.05 to 3 w / v% of xanthan gum and 0.01% to 3 w / v% of guar gum are added and homogenised at a speed of 1 to 5000 RPM, followed by soaking for 0.01 to 168 hours. In the third step 130, the amount of colour is in a range of 0.0001 to and the predefined temperature range is 0 to 150oC. In accordance with the method 100 of the present invention, the second phase 201 that is the final preparation process of the suspension for solution formulation of potassium and magnesium salts is carried out in highly customised equipment. The equipment is made up of a thermoplastic polymer selected from high-density polyethylene (HDPE), polypropylene (PP), polyethylene terephthalate (PET), polystyrene, polycarbonate, and the like with 0.1 cm to 100 cm thickness and 316L stainless steel that resists high salts without causing any corrosion to equipment and without chance of any contamination, black particles, or rust entering into the final suspension for the solution product. The second phase, 201, includes the final preparation steps for preparing the suspension for solution formulation of potassium and magnesium salts. A first step 210 of pulverising potassium chloride involves pulverising potassium chloride in a mill. A second step 220 of slurry formation involves mixing the pulverised potassium chloride into demineralised purified water (DMPW) to obtain a slurry. A third step 230 of addition of magnesium chloride solution involves adding magnesium chloride solution into slurry containing potassium chloride. A fourth step 240 of addition of mixture of preservative and gums involves adding a mixture of sodium benzoate, xanthan gum and guar gum into a slurry. A fifth step 250 of addition of colour involves the addition of a colour solution and a flavouring agent to obtain a uniformly coloured and flavoured suspension. A sixth step 260 of making up the final volume involves preparing the final volume of the formulation to get a final suspension for solution formulation of potassium and magnesium salts. In accordance with the method 100 of the present invention, the second phase 201 includes the following steps: a. a first step 210 of pulverising potassium chloride, b. a second step 220 of slurry formation, c. a third step 230 of addition of magnesium chloride solution, d. a fourth step 240 of addition of mixture of preservative and gum, e. a fifth step 250 of addition of colour and flavour, and f. a sixth step 260 of making up the final volume. The first step 210 of pulverising potassium chloride, includes pulverising potassium chloride in a predefined amount in a mill having non-erosive contact surfaces made up of quality SS 316 L. The second step 220 of slurry formation, includes mixing the pulverised potassium chloride obtained in the first step 210 in demineralised purified water (DMPW) at a predefined high speed with continuous stirring to get a uniform slurry. The third step 230 of addition of magnesium chloride solution, includes adding the solution prepared in the first step 110 of the first phase 101 to the slurry of the second step 220 of the second phase 201 at a predefined high speed with continuous stirring to get a uniform slurry. The fourth step 240 of addition of mixture of preservative and gum, includes adding of the solution prepared in the second step 120 of the first phase 101 to the slurry of the third step 230 of the second phase 201 at a predefined high speed with continuous stirring to get a suspension. The fifth step 250 of addition of colour and flavour, includes adding the colour solution prepared in the third step (130) to the slurry obtained in the fourth step (240), along with a predefined amount of flavour or essence, at a predefined high stirring speed with continuous stirring, to obtain a uniform, coloured, and flavoured suspension. The sixth step 260 of making up the final volume includes preparing the final volume of the formulation by continuous stirring at a predefined high speed to get a final uniform suspension for solution formulation of potassium and magnesium salts of predefined reversible viscosity. In accordance with the present invention, in the first step 210, the predefined amount of potassium chloride is 15–95 w / v%, and the resultant particle size of the pulverised potassium chloride obtained is such that 100% of the potassium chloride passes through a 40-mesh sieve as per the American Standard Test Sieve Series (ASTM), corresponding to a particle size of less than 420 microns (µm). Furthermore, the particle size distribution of potassium chloride is defined by D10 ≥ 50 µm, D50 between 100 and 250 µm, and D90 ≤ 400 µm. According to the ASTM standard, mesh number inversely correlates with sieve opening size; higher mesh numbers indicate finer sieve openings permitting smaller particle sizes to pass, whereas lower mesh numbers correspond to coarser openings allowing larger particles. In the second step 220, the pulverised potassium chloride is mixed at the predefined high speed of 1 - 5000 RPM. In the third step 230, the predefined high speed is 1 - 5000 RPM to get a uniform slurry. In the fourth step 240, the predefined high speed is 1 - 5000 RPM to get a suspension. In the fifth step 250, predefined amount of flavour or essence is 0.001 to 10 w / v% and the predefined high speed to get the final uniform coloured and flavoured suspension for solution formulation is 1-5000 RPM. In the sixth step 260, the predefined high speed is 1-5000 RPM to get a final uniform suspension for solution formulation of potassium and magnesium salts of the predefined reversible viscosity of 150 to 800 centipoise. In accordance with the preferred embodiment, the suspension for solution formulation is prepared by diluting one part by volume of the suspension with not less than four parts by volume of water, thereby resulting in a concentrated aqueous solution. For example, 25 mL of the suspension is diluted in not less than 100 mL of water. However, prior to administration, the resulting solution may be further diluted, and the dosing adjusted based on the specific therapeutic needs of the patient, as exemplified in Examples 7 to 10. In accordance with an alternate embodiment of the present invention, the first step 210 involves pulverising potassium chloride by wet grinding. The potassium chloride is pulverised by a slurry method using wet grinding, preferably employing a colloidal mill, to obtain a fine suspension. In this embodiment, the resultant particle size is such that 100% of the particles pass through a 40-mesh sieve, corresponding to a particle size of less than 420 microns (µm), as per the American Standard Test Sieve Series (ASTM). Further, in accordance with one embodiment of the present invention, potassium chloride is used in a form such that the particle size passes through more than a 10-mesh sieve, in accordance with the American Standard Test Sieve Series (ASTM). In this embodiment, a suspension for solution formulation is prepared using the potassium chloride having the particle size of more than a 10-mesh sieve as per the American Standard Test Sieve Series (ASTM). In accordance with another embodiment of the present invention, potassium chloride is used in a form such that the particle size passes through less than a 10- mesh sieve, in accordance with the American Standard Test Sieve Series (ASTM). In this embodiment, a suspension for solution formulation is prepared using potassium chloride having the specified coarser particle size that is less than a 10- mesh sieve as per the American Standard Test Sieve Series (ASTM). In accordance with an alternate embodiment, the formulation of suspension for solution of high concentrations of potassium and magnesium salts of the present invention is used for humans to manage hypokalemia, hypokalemia with hypomagnesemia, and hypertension. In accordance with an alternate embodiment, the formulation of suspension for a solution of high concentrations of potassium and magnesium salts of the present invention is used for agricultural purposes. Referring to FIG.1, a theoretical illustrative representation of the finished suspension for solution formulation including mesh of xanthan gum and guar gum with suspended potassium chloride particles in accordance with the present invention is shown. In accordance with the present invention, the guar gum 301 solution show the presence of entanglement and the formation of a viscoelastic gel- like structure, while xanthan gum 304 solution behaves as weak gel. The entire arrangement traps a weak gel of xanthan gum within a mesh of guar gum's polysaccharide chains. Furthermore, by inducing physical separation, this system contributes to the formation of a potassium chloride particle 308 suspension formulation that is re- suspendable. Additionally, xanthan gum 304 and guar gum mesh 301 with suspended potassium chloride particles 308 in the final suspension for solution formulation forms a weak gel structure that liquefies when the bottle is shaken but is sufficient to cushion the suspended solids during their separation. EXAMPLES: Only a few examples and implementations are disclosed. Variations, modifications, and enhancements to the described examples and implementations and other implementations can be made based on what is disclosed. Examples are set forth herein below and are illustrative of different amounts and types of reactants and reaction conditions that can be utilized in practicing the disclosure. It will be apparent, however, that the disclosure can be practiced with other amounts and types of reactants and reaction conditions than those used in the examples, and the resulting devices various different properties and uses in accordance with the disclosure above and as pointed out hereinafter. Example 1: A suspension for solution formulation of potassium and magnesium salts The suspension for solution formulation of potassium and magnesium salts is as provided below in Table no.1: Sr No Active Ingredients Quantity / 5ml 1 Potassium Chloride IP 4.0 gm 2 Magnesium Chloride IP 0.5 gm 3 Xanthan Gum 9 mg 4 Guar Gum 4.5 mg 5 Sodium Benzoate IP 1.0 mg 6 Colour: Sunset Yellow FCF I.H. 0.300 mg 7 Essence: Raspberry I.H 0.020 ml 8 Demineralised Purified Water IP q.s Example 2: Suspension for solution formulations of potassium and magnesium salts The suspension for solution formulation having formulations 1, 2, 3 and 4 of potassium and magnesium salts are as provided below in Table no.2: Formulati Formulation Formulation Formulation Sr Active on 1 2 3 4 No Ingredients Quantity / Quantity / Quantity / Quantity / 5ml 5ml 5ml 5ml 1 Potassium 2 gm 3 gm 4 gm 5 gm Chloride IP 2 Magnesium 0.04 gm 0.06 gm 0.08 gm 1 gm Chloride IP 3 Xanthan 9 mg 10 mg 12mg 14mg Gum 4 Guar Gum 4.5 mg 8mg 9mg 10mg 5 Sodium 1.0 mg 1.0 mg 2% w / v 0.09 % w / v Benzoate IP Polysorbates ---- ---- ---- 0.05% w / v 6 (as individual or as mixture) Colour: 0.300 mg 0.300 mg 0.300 mg 0.300 mg 7 Sunset Yellow FCF I.H. Essence: 0.020 ml 8 Raspberry 0.020 ml 0.020 ml 0.020 ml I.H Demineralise q.s q.s q.s q.s 9 d Purified Water IP Example 3: A suspension for solution formulation of potassium and magnesium salts containing carboxymethyl celluloses The suspension for solution formulation of potassium and magnesium salts containing carboxymethyl celluloses is as provided below Table no.3: Sr No Active Ingredients Quantity / 5ml 1 Potassium Chloride IP 4.5gm 2 Magnesium Chloride IP 1.5gm 3 Xanthan Gum 15mg 4 Guar Gum 10mg 5 Carboxymethyl Celluloses or any grade as individual or mixture 5mg Sodium Benzoate 6 OR any water-soluble preservative 0.01% w / v as individual or mixture 7 Polysorbates as individual or as mixture 2 % w / v 8 Colour: Sunset Yellow FCF I.H. 0.300 mg 9 Essence: Raspberry I.H 0.020 ml 10 Demineralised Purified Water IP q.s Example 4: Preparation of the suspension for solution formulation containing potassium chloride having particle size passing through more than 10 mesh (ASTM) The suspension for solution formulation containing potassium chloride having particle size passing through more than 10 mesh (ASTM) was prepared as follows: i. Potassium chloride crude solids / crystals were pulverised using a mill till the desired particle size was achieved. ii. The pulverised potassium chloride of the desired particle size more than 10 mesh (ASTM) was mixed with demineralised purified water (DMPW) at high speed under continuous stirring to obtain a uniform slurry. iii. To the slurry, the magnesium chloride solution was added. iv. To the mixture prepared in the third step, a mixture of sodium benzoate and gums such as xanthan gum and guar gum were added with continuous stirring to get a suspension. v. To the suspension, other excipients such as colour and flavour were added. vi. The final volume of the suspension was made up and stirred for a sufficient period of time to get a uniform suspension. Example 5: Preparation of the suspension for solution formulation containing chloride having particle size passing through less than 10 mesh The suspension for solution formulation containing potassium chloride having particle size less than 10 mesh (ASTM) was prepared as follows: i. Potassium chloride crude solids / crystals were pulverised using a mill till the desired particle size was achieved. ii. The pulverised potassium chloride of the desired particle size of less than 10 mesh obtained was mixed with demineralised purified water (DMPW) at a high speed with continuous stirring to get a uniform slurry. iii. To the slurry, the magnesium chloride solution was added. iv. To the mixture prepared in the third step, a mixture of sodium benzoate and gums such as xanthan gum and guar gum were added with continuous stirring to get a suspension. v. To the suspension, other excipients such as colour and flavour were added. vi. The final volume of the suspension was made up and stirred for a sufficient period of time to get a uniform suspension. Example 6: Pulverization of potassium chloride by slurry method using wet grinding – colloidal mill The pulverization of potassium chloride by slurry method using wet grinding – colloidal mill was carried out as follows: i. To the demineralised purified water (DMPW), potassium chloride was added to get a uniform slurry. ii. The slurry prepared in the first step was passed through the wet grinding – colloidal mill till the desirable particle size slurry was obtained. iii. To the uniform slurry obtained in the second step, the magnesium chloride solution was added. iv. To the mixture prepared in the third step, a mixture of sodium benzoate and gums such as xanthan gum and guar gum were added with continuous stirring to get a suspension. v. To the suspension, other excipients such as colour and flavour were added. vi. The final volume of the suspension was made up and stirred for a sufficient period of time to get a uniform suspension. Example 7: Preparation of final solution before administration To administer a suspension for solution formulation of potassium chloride and magnesium chloride for patients, the measured dose was added to water. The suspension dissolves immediately, producing a clear liquid solution. As shown in FIG. 2, the final solution before administration for usage was prepared as per the dilution directions as follows: 1. The bottle was shaken vigorously by inverting the bottle for 5-10 times. 2. 10 ml to 25 ml of suspension (or as required) was measured. 3. The suspension was diluted by mixing it into 10 -25 litres of water. 4. It was stirred well before using, ensuring proper mixing. Example 8: Dilution for administering a suspension for solution formulation of potassium chloride and magnesium chloride to patients for veterinary purposes. I. For Recumbent Animal (cattle / cows / buffalo / horses / equines) • The method of dilution before administering a suspension for solution formulation of potassium chloride and magnesium chloride was carried out in three ways as follows: 1. 5 to 50 ml of suspension diluted in 1000 ml to 50 litres of water and administered using a bucket or flowing water feeding system. 2. 50 to 1000 ml of suspension diluted in 50 litres to 1000 litres of water and administered using bucket or flowing water feeding system. 3. 5 to 50 ml of suspension diluted in 500 ml to 1000 ml and administered by direct feeding bottle. • Recumbent animals such as cattle / cows / buffalo / horses / equines for administering a suspension for solution formulation of potassium chloride and magnesium chloride, 5-20 ml of suspension was diluted in 10-100 litres of water for improved milk yield. II. For Dogs In dogs, for administering a suspension for solution formulation of potassium chloride and magnesium chloride, 0.5 - 1.5 ml of suspension was diluted in 200 ml of water. III. For Pigs / Swine In pigs / swine, for administering a suspension for solution formulation of potassium chloride and magnesium chloride, 0.5 - 5 ml of suspension was diluted in 200 ml to 2000 ml of water. IV. For Sheep / Goat In sheep / goats, for administering a suspension for solution formulation of potassium chloride and magnesium chloride, 0.5 - 5 ml of suspension was diluted in 200 ml to 500 ml of water. V. For Cats In cats, for administering a suspension for solution formulation of potassium chloride and magnesium chloride, 0.1 - 0.5 ml of suspension was diluted in 50 ml of water. VI. For Chicken / Poultry In chicken / poultry, for administering a suspension for solution formulation of potassium chloride and magnesium chloride, 10 to 1000 ml of suspension was diluted in 50 to 1000 litres of water and was administered using a flowing water feeding system. Example 9: Dilution for administering a suspension for solution formulation of potassium chloride and magnesium chloride to manage hypokalemia, hypokalemia with hypomagnesemia, and hypertension in humans. The dilution for administering a suspension for solution formulation of potassium chloride and magnesium chloride was carried out in two ways as follows: 1. 0.5 -1.5 ml of suspension was diluted in 200 ml of water and administered sip by sip. 2. 5 to 10 ml was diluted in 1000 to 2000 ml water and was administered sip by sip. Example 10: Dilution for administering a suspension for solution formulation of potassium chloride and magnesium chloride for agricultural purposes. The dilution for administering a suspension for solution formulation of potassium chloride and magnesium chloride: I. For Decorative Plants The dilution for administering a suspension for solution formulation of potassium chloride and magnesium chloride: 0.5 to 20 ml of suspension was diluted in 1000 to 5000 litres of water for irrigation / drip irrigation. II. For Field Plants The dilution for administering a suspension for solution formulation of potassium chloride and magnesium chloride: 10 to 1000 ml of suspension was diluted in 1000 to 10,000 litres of water for irrigation / drip irrigation. Advantageously, the suspension for solution formulation of potassium chloride and magnesium chloride salt of the present invention enables delivery of very high concentrations of freely soluble salts to meet the daily requirement of salts for patients without compromising its stability or the safety of the patients. Further, the resulting mixture prepared by dilution prior to administration is palatable and ensures gastrointestinal safety due to the net concentration of salt becoming palatable. Furthermore, in the present invention, a single formulation provides both the salts needed to treat a potassium deficiency. For the potential user or patient or animals, this increases safety, effectiveness, and usability, as well as cost efficiency. Moreover, the suspension for solution formulation of the present invention eliminates the problems associated with both oral dosage forms, such as tablets or capsules, and solution formulations of freely soluble salts. Additionally, the suspension for solution formulation of the present invention is used for agricultural purposes and for human use as an adjuvant to manage hypokalemia, hypokalemia with hypomagnesemia, and hypertension. The embodiments were chosen and described in order to best explain the principles of the present invention and its practical application, to thereby enable others, skilled in the art to best utilize the present invention and various embodiments with various modifications as are suited to the particular use contemplated. It is understood that various omission and substitutions of equivalents are contemplated as circumstance may suggest or render expedient, but such are intended to cover the application or implementation without departing from the scope of the present invention.

Claims

Claims:

1. A suspension for solution formulation of potassium and magnesium salts comprising: a) potassium chloride at a concentration of 15 to 95 w / v%; b) magnesium chloride at a concentration of 0.5 to 95 w / v%; c) a first polysaccharide gum that is xanthan gum at a concentration of 0.05–3% w / v and a second polysaccharide gum that is guar gum at a concentration of 0.01–3% w / v; d) a preservative selected from sodium benzoate or benzoic acid at a concentration of 0.001 to 10 w / v%; e) a color at a concentration of 0.0001–10% w / v, an essence at a concentration of 0.001–10% v / v; and f) demineralised purified water q.s., wherein the suspension (i) has a Brookfield viscosity of 150–800 cP, (ii) remains free of visible crystallization and phase separation after storage, and (iii) forms a clear solution when diluted at a ratio of ≥1:4 (v / v) with potable water.

2. The suspension for solution formulation of potassium and magnesium salts as claimed in claim 1, wherein the preservative being selected from benzoic acid, sodium benzoate and the like; the colour being selected from sunset yellow FCF I.H. and the like, the synthetic dyes being selected from categories azos, nitros, nitrosos, trimethylmethane, phthaleins, indigos,anthraquinones, and the like; and the essence being selected from raspberry I.H., citrous, fruity, and milky flavours and the like.

3. The suspension for solution formulation of potassium and magnesium salts as claimed in claim 1, wherein the formulation further comprises polysorbates, individually or as a mixture, at a concentration of 0.05–2% w / v to enhance wetting.

4. The suspension for solution formulation of potassium and magnesium salts as claimed in claim 1, wherein 100% of potassium chloride particles being pass through a 40-mesh sieve (<420 µm) and having a particle size distribution characterized by D10 ≥ 50 µm, D50 between 100 and 250 µm, and D90 ≤ 400 µm.

5. The suspension for solution formulation of potassium and magnesium salts as claimed in claim 1, wherein the formulation being filled in containers composed of a thermoplastic polymer selected from high- density polyethylene (HDPE), polypropylene (PP), polyethylene terephthalate (PET) or the like, and the contact surfaces of the process equipment being made of 316L stainless steel to prevent corrosion or contamination.

6. A method (100) of preparation of the suspension for solution formulation of potassium and magnesium salts as claimed in claim 1, wherein the method 100 including a first phase (101) of a series of prerequisite steps being carried out before the preparation of the suspension for solution formulation of potassium and magnesium salts and a second phase (201)of a series of steps being carried out for the final preparation of the suspension for solution formulation of potassium and magnesium salts.

7. The method (100) of preparation of the suspension for solution formulation of potassium and magnesium salts as claimed in claim 6, wherein the first phase (101) including the following steps: a. a first step (110) of dissolving magnesium chloride; b. a second step (120) of dissolving preservative with gums; and c. a third step (130) of dissolving colour.

8. The method (100) of preparation of the suspension for solution formulation of potassium and magnesium salts as claimed in claim 7, wherein in the first step (110), 0.5 to 40 w / v % of magnesium chloride being dissolved in demineralised purified water (DMPW) at room temperature.

9. The method (100) of preparation of the suspension for solution formulation of potassium and magnesium salts as claimed in claim 7, wherein in the second step (120), 0.001 to 10 w / v% of preservative selected from sodium benzoate, benzoic acid and the like being dissolved in demineralised purified water (DMPW) at 0 to 150°C, and to this, 0.05 to 3 w / v% of xanthan gum and 0.01 to 3 w / v % of guar gum being added following stirring and homogenization at a speed of 1 to 5000 RPM , followed by soaking for 0.01 to 168 hours.

10. The method (100) of preparation of the suspension for solution formulation of potassium and magnesium salts as claimed in claim 7,wherein in the third step (130), 0.0001 to 10 w / v% of colour being dissolved in demineralised purified water (DMPW) at 0 to 150°C.

11. The method (100) of preparation of the suspension for solution formulation of potassium and magnesium salts as claimed in claim 6, wherein the second phase (201) including the following steps: a. a first step (210) of pulverising potassium chloride; b. a second step (220) of slurry formation; c. a third step (230) of addition of magnesium chloride solution; d. a fourth step (240) of addition of mixture of preservative and gum; e. a fifth step (250) of addition of colour and flavour; f. a sixth step (260) of making up the final volume.

12. The method (100) of preparation of the suspension for solution formulation of potassium and magnesium salts as claimed in claim 11, wherein in the first step (210), 15 – 95 w / v% of potassium chloride being pulverised using a mill having non-erosive contact surfaces made up of quality SS 316 L for obtaining potassium chloride of resultant particle size less than 40 mesh of the American Standard Test Sieve Series [ASTM].

13. The method (100) of preparation of the suspension for solution formulation of potassium and magnesium salts as claimed in claim 11, wherein in the second step (220), the pulverised potassium chloride obtained in the first step (210) being mixed into demineralised purified water (DMPW) at the speed of 1-5000 RPM with continuous stirring to get a uniform slurry.

14. The method (100) of preparation of the suspension for solution formulation of potassium and magnesium salts as claimed in claim 11, wherein in the third step (230), magnesium chloride solution prepared in the first step (110) being added to the slurry of the second step (220) at a high speed of 1-5000 RPM with continuous stirring to get a uniform slurry.

15. The method (100) of preparation of the suspension for solution formulation of potassium and magnesium salts as claimed in claim 11, wherein in the fourth step (240), the mixture of preservative selected from sodium benzoate, benzoic acid and the like and gum prepared in the second step (120) being added at a high speed of 1-5000 RPM with continuous stirring to get a suspension.

16. The method (100) of preparation of the suspension for solution formulation of potassium and magnesium salts as claimed in claim 11, wherein in the fifth step (250), the colour solution prepared in the third step (130) being added to the slurry of the fourth step (240) along with 0.001 to 10 w / v% of flavour or essence at a high speed of 1-5000 RPM with continuous stirring to get a uniform coloured and flavoured suspension.

17. The method (100) of preparation of the suspension for solution formulation of potassium and magnesium salts as claimed in claim 11, wherein in the sixth step (260), the final volume of the suspension beingmade up by stirring at 1-5000 RPM to get a final uniform suspension for solution formulation of potassium and magnesium salts.

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