Field of Invention:

The present invention relates to a stable liquid pharmaceutical composition comprising alkali metal citrates with Vitamin B6 compound useful for the treatment of dysuria (Moothra Krichra OR burning urination), renal tubular acidosis and for prevention of recurrence of urinary stones (urolithiasis).

Background of Invention:

Dysuria refers to painful urination. This is typically described to be a burning or stinging sensation. It is most often a result of a urinary tract infection. It may also be due to an STD, bladder stones, bladder tumors, and virtually any condition of the prostate. It can also occur as a side effect of anticholinergic medication used for Parkinson's disease.
Medically, dysuria is not treated as a disease in itself It is actually a symptom of some other underlying disease, which will most probably be sexual in origin. Hence, there is no uniform method for treatment in patients of dysuria. The treatment is done according to the symptoms; such as, heat, as in a warm sitz bath, may be recommended for some causes of painful urination. Antibiotics may be prescribed for infections. Medications to stop the growth of kidney stones may be prescribed, as well as medications to stop spasms caused by kidney stones or infection.

Other treatments will vary greatly depending on the cause of the pain. Those with cancer may need surgery, chemotherapy, or radiation therapy. Surgery may be needed for those having kidney stones or damage to the urinary .tract from an injury or recurrent infections.

Disorders affecting the overall ability of the renal tubules either to secrete hydrogen ions (H*) or to retain bicarbonate ions (HCO') are known collectively by the term renal tubular acidosis (RTA). The condition was first described clinically in 1935, confirmed as a renal tubular disorder in 1946 and designated "renal tubular acidosis" in 1951.

It is now recognized that RTA comprises a diverse group of disorders affecting either proximal or distal tubular function. In the complete form, they are characteristically associated with the biochemical finding of hyperchloraemic acidosis; the Glomerular Filtration Rate (GFR) is normal or only slightly reduced and there is no significant
retention of anions such as phosphate or sulphate (as found in the acidosis of glomerular impairment).

The average adult diet generates about 1-1.5 mmol H+ per kg body weight, mainly from protein consumption, resulting in the need to excrete up to 100 mmol/day of H+ for a 70 kg man. In unbuffered form, this acid would theoretically produce a pH of 1 in 1 L of urine, but the minimum urine pH achievable physiologically is approximately 4.2. A GFR of 180 L/day results in a cumulative filtered load of 4500 mmol HCO" , and the renal generation and retention of HCO' forms an important part of acid/base balance.

The aims of treatment of RTA are to correct biochemical abnormalities, to improve growth in children, and to prevent the development and progression of clinical features and of renal failure. Treatment consists of correction of pH and electrolyte balance with alkali therapy.
The alkali therapy for RTA treatment consists of the administration of alkali, either as bicarbonate or as something that is converted into bicarbonate rapidly in the body. Since the normal kidney is getting rid of acid continuously, the alkali needs to be given in frequent doses, usually in 3-4 doses a day. Once or twice a day dosing will generally leave the child acidotic (i.e. with high blood levels of acid) for a significant portion of the day, and the symptoms of the disease will continue, especially the problem of growth failure.

Kidney stone formation is the end result of a physicochemical process that involves nucleation of crystals from a supersaturated solution. The common constituents of kidney stones are as follows:

Table Crystalline composition of renal calculi and their frequency

The options for treatment are sodium bicarbonate pills, sodium bicarbonate liquid, sodium citrate liquid, mixed sodium citrate and potassium citrate liquid. In the market bicarbonate pills come as 325 mg and 650 mg (doctors often talk of acid and alkali amounts in terms of mEq which are milliequivalents, and the 650 mg pills are 7.7 mEq each). Sodium citrate is available commercially as Bicitra, which contains 1 mEq of alkali per milliliter. Mixed sodium and potassium citrate is available as Polycitra, which is 2 mEq/ml, one of sodium and one of potassium.

Potassium citrate is indicated for the management of renal tubular acidosis (RTA) with calcium stones, hypocitraturic calcium oxalate nephrolithiasis of any etiology, and uric acid lithiasis with or without calcium stones. Potassium citrate therapy reduces urine calcium excretion and stone formation rates.

Potassium citrate is a white, granular powder or transparent crystals, hygroscopic, very soluble in water, practically insoluble in alcohol. Potassium citrate is available as an oral solution along with the citric acid. The liquid formulation of potassium citrate is official in BP 2005 and USP 27. Potassium Citrate Mixture BP is an oral solution containing 30% w/v of Potassium Citrate and 5% w/v of Citric Acid Monohydrate in a suitable vehicle with a lemon flavor. It is intended to be diluted with water before use.

Potassium citrate and citric acid oral solution is available worldwide from different manufacturers and is indicated for treatment or prevention of hypokalemia and to prevent the formation of certain kinds of kidney stones. Magnesium citrate oral solution USP is
available in the market is made up of magnesium carbonate, citric acid, potassium carbonate and other additives.

Magnesium citrate (200 to 400 mg per day) increases the solubility of calcium oxalate and calcium phosphate. Magnesium citrate is a white, odorless, crystalline powder or granules. Slightly soluble in water, the solubility is increased by addition of citric acid or alkali citrates; soluble in dilute acids. Magnesium citrate is official in USP 26. It comprises 14.5% - 16.4% of Mg, calculated on the dried basis. A 5% suspension in water has a pH of 5.0 to 9.0. Magnesium citrate oral solution USP is a sterilized or pasteurized solution containing, in each 100 ml, not less than 7.59 g of anhydrous citric acid (CeHgOy) and an amount of magnesium citrate equivalent to not less than 1.55 g and not more than 1.9 g of magnesium oxide (MgO). In magnesium citrate for oral solution USP, the content of citric acid anhydrous is between 76.6 to 93.7% of the labeled amount of magnesium citrate.
Though the role of magnesium citrate in renal stones is understood and well known, it is not available in solution form, due to its low solubility in water.

Research conducted with people who have a history of kidney stones which involved administration of a combination of potassium citrate and magnesium citrate, showed a drop in recurrence rate of kidney stones 64% to 13% for those receiving high amounts of both supplements.

Pyridoxine hydrochloride in range of 200 - 400 mg/day, or taken with magnesium, may decrease urinary oxalate levels, which can contribute to a certain type of kidney stones. Recent research has shown the amazing therapeutic success of vitamin B6 (Pyridoxine HCl) in the treatment of kidney stones.

Pyridoxine hydrochloride is one of the compounds that form vitamin B6 group, along with pyridoxal and pyridoxamine. Pyridoxine HCl is available in different dosage forms, such as a tablet, capsule or solution. Pyridoxine HCl is usually safe, at intakes up to 200 mg per day in adults.

Us Patent No. 4888182 titled "Compositions and methods of treating calcium renal stones" discloses use potassium citrate in tablet form for treatment and prevention of calcium renal stones associated with renal tubular acidosis. The dosage scheme as disclosed in US '185 patent requires an administration of 30 - 120 mEq of potassium citrate.

In this context it is desirable to invent a novel composition which provides potassium citrate and magnesium citrate in a single stable oral solution that provides 1 mEq of magnesium, 2 mEq of potassium and 4 mg of pyridoxine hydrochloride per ml.

As can be seen from above mentioned details a triple combination of potassium citrate, magnesium citrate and pyridoxine has not been disclosed in any prior art, consequently instant invention provides an oral solution which comprises potassium citrate, magnesium citrate and pyridoxine in stable liquid composition.

Summary of Invention:
In one aspect the invention relates to stable liquid composition comprising potassium citrate, magnesium citrate and pyridoxine in a single oral solution.

In another aspect invention relates to a process for manufacturing the said novel composition, wherein the insoluble magnesium citrate is dissolved along with potassium citrate and citric acid to give a stable oral liquid composition.

Detailed Description of Invention:

The invention will now be described in details in connection with certain preferred and optional embodiments so that various aspects thereof may be more fully understood and appreciated.

As per the present invention, a stable pharmaceutical liquid composition comprising a plurality of alkali metal citrates, whereby low soluble alkali metal citrates are solubalized by addition of citric acid in combination with Vitamin B6 compound along with pharmaceutically acceptable excipients and process for manufacturing thereof.

"alkali metal citrate" as used in present specification refers to a citric salt of any element selected from group I and group II of the periodic table, which encompasses Lithium (Li), Sodium (Na), Potassium (K), Rubidium (Rb), Caesium (Cs), and Francium (Fr) and also, Beryllium (Be), Magnesium (Mg), Calcium (Ca), Strontium (Sr), Barium (Ba) and Radium (Ra).

"Vitamin B6" and "pyridoxine" are used interchangeably to refer to any compound selected from pyridoxine (PN), pyridoxine 5'-phosphate (PNP), pyridoxal (PL), pyridoxal 5'-phosphate (PLP), pyridoxamine (PM), pyridoxamine 5'-phosphate (PMP), 4-pyridoxic acid (PA).

Citric acid and potassium citrate helps to dissolve and keep magnesium citrate in solution form. The quantity of the citric acid, pH and the processing conditions such as heat and stirring are the critical parameters in the manufacturing of the stable liquid composition of present invention. While manufacturing the stable composition of instant invention the quantity of citric acid necessary to dissolve magnesium citrate is between 1 - 10%, preferably 1 - 5% w/v of the composition. The pH of solution is maintained at 5.0 - 5.5, that keeps magnesium citrate in dissolved form and maintain stability of liquid solution without re-crystallization or precipitation of magnesium citrate and optimum stability of pyridoxine hydrochloride. Further, heating is essential to enhance the solubility of magnesium citrate in the preferred base in presence of citric acid and potassium citrate. The invention also discloses that the temperature of the base is maintained at 70 - 80° C, so as to provide a stable liquid oral solution without re-crystallization of magnesium salt. Stirring should be optimal during to ensure proper mixing and to avoid frothing. The said procedure yields stable liquid composition without re-crystallization or precipitation of magnesium citrate.

In a preferred embodiment, instant invention provides an oral solution comprising 1100 mg of potassium citrate, 375 mg of magnesium citrate and 20 mg of pyridoxine per 5 ml of the preparation, to provide 1 mEq of magnesium, 2 mEq of potassium and 4 mg of pyridoxine per ml. the oral solution.

In further embodiment the oral solution comprises, a base, selected from Sorbitol 70%, glycerin or sucrose; artificial sweetener saccharin sodium; preservatives selected from methyl and propyl paraben and its sodium salt, benzoic acid, sodium benzoate, sorbic acid and its forms, more preferably sodium benzoate; fruit flavors and color caramel for enhanced organoleptic characteristics.

In another embodiment the invention provides a process for manufacturing of the oral solution which comprises dissolving the magnesium citrate comprising at least one base selected from sugar, sorbitol solution, glycerin and propylene glycol in the range of 40 -99.50%. Sweeteners and preservatives are added at the initial or final stage of the preparation. Flavors and color caramel are added at the final stage to enhance the organoleptic characteristics of the preparation.

The alkali metal citrate is selected from Na-citrate, K-citrate or Mg-citrate, more preferably liquid K- and Mg-citrate or combinations thereof. The Vitamin B6 compound used in instant invention is pyridoxine. The said composition further comprises citric acid in the range of 1% - 10% preferably, 1% - 5%. The pH of the said liquid composition is maintained in range of 5.0 - 5.5. The liquid composition of the instant invention comprises pharmaceutically acceptable exciplents such as at least one base, at least one preservative and at least one sweetener, whereby at least one base is selected from sorbitol 70%, sucrose, glycerin, propylene glycol; at least one preservative is selected from methyl paraben, propyl paraben and its sodium saUs, benzoic acid, sodium benzoate; and the sweetener is saccharin sodium.

The process for manufacturing instant invention comprises steps of;

FOR SUGAR FREE ORAL SOLUTION

(a) Weighing sorbitol solution and glycerin in a suitable vessel and mix; to it add saccharin sodium and sodium benzoate dissolved in purified water.

(b) Dissolving citric acid in purified water and adding the same to solution of step (a). Adding potassium citrate in the solution of step (a) to get a clear solution.
(c) Heating the contents of step (b) to 70 - 80° C and dissolving magnesium citrate in it and further cooling at room temperature.

(d) Dissolving pyridoxine hydrochloride in purified water and adding it to solution of step (c) under mixing.

(e) Adding caramel and flavors to the contents of step (d) and making up the volume with purified water.

FOR ORAL SOLUTION WITH SUGAR:

(a) Preparing sugar syrup (50% w/v) and mixing the sugar syrup to glycerin.
(b) Dissolving saccharin sodium and sodium benzoate in purified water and adding it to the solution of step (a).
(c) Dissolving citric acid in purified water and adding it to solution of step (b). Adding potassium citrate to solution of step (b) to get a clear solution.
(d) Heating the contents of step (c) to 70 - 80° C and dissolving magnesium citrate In to it and further, cooling to room temperature
(e) Dissolving pyridoxine hydrochloride in purified water and adding it to solution of step (d) under mixing.
(f) Adding caramel and flavors to the contents of step (e) making up the volume with purified water.

The instant invention is more specifically explained by following examples. However, it should be understood that the scope of the present invention is not limited by the examples in any manner. It will be appreciated by any person skilled in this art that the present invention includes following examples and further can be modified and altered within the technical scope of the present invention.

Examples
Examples 1 to 8

Table 1: for composition of stable liquid formulation

Manufacturing process employed for production of Examples 1-8 Example 1:

500.0 g sorbitol solution and 100.0 g of glycerin are taken and mixed well. 1.0 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 6.0 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is slowly added to the sorbitol solution under stirring, to get a clear solution. 75.2 g of magnesium citrate is added to the above solution under stirring, till it gets dissolved in the Sorbitol base. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Example 2:
Sugar syrup is prepared with 500.0 g of sucrose in quantity sufficient of purified water. 100.0 g of glycerin is added and mixed well. 1.0 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 12.0 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is slowly added to the sorbitol solution under stirring, to get a clear solution. 75.2 g of magnesium citrate is added to the above solution under stirring, till it gets dissolved in the Sorbitol base. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Example 3:
500.0 g sorbitol solution and 100.0 g of glycerin are taken and mixed well. 1.5 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 20.0 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is slowly added to the sorbitol solution under stirring, to get a clear solution. 75.2 g of magnesium citrate is added to the above solution under stirring, till it gets dissolved in the Sorbitol base. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Example 4
400.0 g sorbitol solution and 100.0 g of glycerin are taken and mixed well. 1.5 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 16.0 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is slowly added to the sorbitol solution under stirring, to get a clear solution. 75.2 g of magnesium citrate is added to the above solution under stirring, till it gets dissolved in the Sorbitol base. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Example 5
400.0 g sorbitol solution and 100,0 g of glycerin are taken and mixed well. 1.5 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 20.0 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is. slowly added to the sorbitol solution under stirring, to get a clear solution. 75.2 g of magnesium citrate is added to the above solution under stirring, till it gets dissolved in the Sorbitol base. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Example 6
600.0 g sorbitol solution and 100.0 g of glycerin are taken and mixed well. 0.5 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 25.0 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is slowly added to the sorbitol solution under stirring, to get a clear solution. 75.2 g of magnesium citrate is added to the above solution under stirring, till it gets dissolved in the Sorbitol base. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Example 7
600,0 g sorbitol solution and 100.0 g of propylene glycol are taken and mixed well. 0.5 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 16.0 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is slowly added to the sorbitol solution under stirring, to get a clear solution. 75.2 g of magnesium citrate is added to the above solution under stirring, till it gets dissolved in the Sorbitol base. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Example 8
500.0 g sorbitol solution and 100.0 g of glycerin are taken and mixed well. 1.0 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 20.0 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is slowly added to the sorbitol solution under stirring, to get a clear solution. The solution is heated to 70 - 80° C. 75.2 g of magnesium citrate is added to the above solution under stirring, till it gets dissolved in the Sorbitol base. Cool to room temperature. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution at room temperature. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Table 1A: for composition of stable liquid formulation: Example 9 to 16

Manufacturing process employed for production of Examples 9-16

Example 9:
995.0 g sorbitol solution and 100,0 g of glycerin are taken and mixed well. 1.0 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 16.0 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is slowly added to the sorbitol solution under stirring, to get a clear solution. 75.2 g of magnesium citrate is added to the above solution under stirring, till it gets dissolved in the Sorbitol base. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Example 10:
995.0 g sorbitol solution and 100.0 g of glycerin are taken and mixed well. 1.0 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 30.0 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is slowly added to the sorbitol solution under stirring, to get a clear solution. 75.2 g of magnesium citrate is.added to the above solution under stirring, till it gets dissolved in the Sorbitol base. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Example 11:
995.0 g sorbitol solution and 100.0 g of glycerin are taken and mixed well. 1.0 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 30.0 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate Is slowly added to the sorbitol solution under stirring, to get a clear solution. 82.72 g of magnesium citrate is added to the above solution under stirring, till It gets dissolved in the Sorbitol base. Pyridpxine hydrochloride Is dissolved in purified water and added to the bulk solution. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Example 12;
500.0 g sorbitol solution and 100.0 g of glycerin are taken and mixed well. 1.0 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 37.5 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is slowly added to the sorbitol solution under stirring, to get a clear solution. 82.72 g of magnesium citrate is added to the above solution under stirring, till it gets dissolved in the Sorbitol base. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution at room, temperature. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Example 13:
400.0 g sorbitol solution and 100.0 g of glycerin are taken and mixed well. 1.0 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 37.5 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is slowly added to the sorbitol solution under stirring, to get a clear solution. The solution is heated to 70 - 80° C. 82.72 g of magnesium citrate is added to the above solution under stirring, till it gets dissolved in the Sorbitol base. Cool to room temperature. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution at room temperature. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Example 14:
500.0 g sorbitol solution and 100.0 g of glycerin are taken and mixed well. 1.0 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 37.5 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is slowly added to the sorbitol solution under stirring, to get a clear solution. The solution is heated to 70 - 80° C. 82.72 g of magnesium citrate is added to the above solution under stirring, till it gets dissolved in the Sorbitol base. Cool to room temperature. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution at room temperature. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Example 15:
300.0 g sorbitol solution and 100.0 g of glycerin are taken and mixed well. 1.5 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 40.0g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is slowly added to the sorbitol solution under stirring, to get a clear solution. The solution is heated to 70 - 80° C. 82.72 g of magnesium citrate is added to the above solution under stirring, till it gets dissolved in the Sorbitol base. Cool to room temperature. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution at room temperature. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Example 16:
200.0 g sorbitol solution is taken in a suitable vessel. 2.0 g of saccharin sodium and 2.0 g sodium benzoate are dissolved in purified water and added to Sorbitol base. 40.0 g of citric acid is dissolved in water and added to the above base. 216.6 g of potassium citrate is slowly added to the sorbitol solution under stirring, to get a clear solution. The solution is heated to 70 - 80° C. 82,72 g of magnesium citrate is added to the above solution under stirring, til! it gets dissolved in the Sorbitol base. Cool to room temperature. Pyridoxine hydrochloride is dissolved in purified water and added to the bulk solution at room temperature. Colour caramel and flavours are added to the above preparation and volume is made up to 1.0 liter with purified water and stirred well.

Table 2 shows the stability data for each of above mentioned compositions

Table 2: Stability Data

We Claim:

1. A stable liquid composition comprising a plurality of alkali metal citrates, wherein low soluble alkali metal citrates are solublized by addition of citric acid in combination with Vitamin B6 compound along with pharmaceutically acceptable excipients.

2. A stable liquid composition as claimed in Claim 1, wherein the said liquid composition is in the form of sugar solution or sugar free solution.

3. A stable liquid composition as claimed in Claim 1, wherein alkali metal citrate is selected form sodium citrate, potassium citrate and magnesium citrate; more preferably combination potassium citrate and magnesium citrate.

4. A stable liquid composition as claimed in Claim 1, wherein vitamin B6 compound is pyridoxine, derivatives or pharmaceutically acceptable salts thereof.

5. A stable liquid composition as claimed in Claim 1, wherein citric acid is in range of 1% to 10%w/v, preferably 1% to 5%w/v.

6. A stable liquid composition as claimed in Claim 1, wherein the pH of liquid composition is in the range of 5.0 to 5.5.

7. A stable liquid composition as claimed in Claim 1, wherein pharmaceutical excipients comprises at least one base, at least one preservative and at least one sweetener.

8. A stable liquid composition as claimed In Claim 1 and 6, wherein at least one base Is selected from sorbitol 70%, sucrose, glycerin and propylene glycol.

9. A stable liquid composition as claimed in Claim 1 and 6, wherein preservative is selected from methyl paraben, propyl paraben and its sodium salts; benzoic acid, sodium benzoate; more preferably sodium benzoate.

10. A stable liquid composition as claimed in Claim 1 and 6, wherein sweetener is saccharin sodium.

11. A stable liquid composition as claimed in Claim 1 and 2, wherein the sugar free liquid composition is manufactured by a process comprising following steps:

(a) Weighing sorbitol solution and glycerin in a suitable vessel and mix; to it add
saccharin sodium and sodium benzoate dissolved in purified water.

(b) Dissolving citric acid in purified water and adding the same to solution of step (a).
Adding potassium citrate in the solution of step (a) to get a clear solution.

(c) Heating the contents of step (b) to 70 - 80° C and dissolve magnesium citrate in it and further, cooling to room temperature.

(d) Dissolving pyridoxine hydrochloride in purified water and adding it to solution of step (c) under mixing.

(e) Adding caramel and flavors to the contents of step (d) and making up the volume
with purified water.

12. A stable liquid composition as claimed in Claim 1 and 2, wherein the liquid
composition with sugar solution is manufactured by a process comprising following
steps:

(a) Preparing sugar syrup (50% w/v) and mixing glycerin.

(b) Dissolving saccharin sodium and sodium benzoate in purified water and adding it
to the solution of step (a).

(c) Dissolving citric acid in purified water and adding it to solution of step (b).
Adding potassium citrate to solution of step (b) to get a clear solution.

(d) Heating the contents of step (c) to 70-80° C and dissolve magnesium citrate in to
it and further, cooling to room temperature

(e) Dissolving pyridoxine hydrochloride in purified water and adding it to solution of step (d) under mixing..

(f) Adding caramel and flavors to the contents of step (e) making up the volume with purified water.