FIELD OF THE INVENTION

The present invention relates to oral controlled release compositions comprising potassium chloride. The present invention also relates to improved process for preparing oral controlled release compositions comprising potassium chloride. The present invention further relates to methods of treatment of hypokalemia with or without metabolic alkalosis using oral controlled release compositions comprising potassium chloride.

BACKGROUND OF THE INVENTION

In recent years, studies of the potential pathogenic role of potassium deficiency in various medical conditions have underscored the importance of preventing or correcting the deficiency. Potassium depletion is one of the most common electrolyte abnormalities encountered in clinical practice. Normal serum potassium levels are considered to lie roughly between 3.6 and 5.0 mmol/L. More than 20% of hospitalized patients have hypokalemia, widely defined as a serum potassium level of less than 3.5 mmol/L.

Because potassium is a major intracellular cation, the tissues most severely affected by potassium imbalance are muscle and renal tubular cells. Manifestations of hypokalemia include generalized muscle weakness, paralytic ileus, and cardiac arrhythmias (atrial tachycardia with or without block, atrioventricular dissociation, ventricular tachycardia, and ventricular fibrillation).

Potassium salts include potassium chloride, potassium phosphate, and potassium bicarbonate. Potassium phosphate is primarily found in food, and potassium bicarbonate is recommended when potassium depletion occurs during metabolic acidosis (pH 7.4). In most of the cases, potassium chloride is used because of its unique effectiveness against the most common causes of potassium depletion. Potassium chloride is available in either liquid or tablet formulations and all potassium formulations are readily absorbed. Although liquid forms may be less expensive, they have a strong, unpleasant taste and often are not well tolerated.

Oral solid dosage forms of potassium chloride are used for the treatment of hypokalemia with or without metabolic alkalosis. Solid dosage forms include immediate release, sustained release and controlled release dosage forms.

The pharmaceutical industry employs various methods for compounding pharmaceutical agents in tablet formulations, the most preferable method being granulation.
Granulation is a process whereby granules are formed from a bulk drug substance with or without excipients to improve the properties of the bulk drug or formulation. Granules are preparations consisting of solid, dry agglomerates of powder particles sufficiently robust to withstand handling.

Wet granulation is distinguished from dry granulation in that a granulating liquid, such as water, organic liquids or mixtures thereof, are used in wet granulation to produce granules. The advantages of wet granulation include improvement of the cohesiveness and compatibility of powders, increase in density and good distribution providing uniform content of micronized or finely milled low-dosage drugs, reduction of dust and airborne contamination, and prevention of segregation of components.

Melt granulation is one of the most widely applied processing techniques in the pharmaceutical manufacturing operations. Melt granulation is a process by which granules are obtained through the addition of either a molten binder or a solid binder which melts during the process. This process is also called melt agglomeration and thermoplastic granulation. The process utilizes materials that are effective as granulating fluids when they are in the molten state. Cooling of the agglomerated powders and solidification of the resultant molten materials completes the granulation process.

This technique is better than conventional granulation, because neither water nor organic solvents are used for granulation. The process is less time consuming and uses less energy than wet granulation. Melt granulation is a useful technique to enhance the solubility and dissolution rate of poorly water-soluble drug. The granules prepared by this method show good flow properties and good compressibility with low weight variation and low friability.

Following patents/patent publications discloses potassium chloride formulations and process for their preparation.

US 3,538,214 discloses composition comprising potassium chloride tablets comprising core coated with plastic substance and film modifying agent.

US 4,140,756 discloses composition comprising tablets for continuous release of potassium chloride comprising polymer coated core containing potassium chloride and stearic acid.

US 4,235,870 discloses composition comprising potassium chloride, cetyl alcohol, hydroxyethyl cellulose and talc.

US 4,557,925 discloses composition comprising membrane-coated potassium chloride tablets comprising terpolymer, micronized powdered saccharose, acetyl tributyl citrate, blown castor oil, sodium bicarbonate and acetone.

US 4,572,833 discloses coating of potassium chloride crystals using film coating mixture prepared from paraffin, acetyl tributyl citrate, ethylcellulose, silicium dioxide and isopropanol. Tablets were prepared from talc, film-coated potassium chloride crystals, microcrystalline cellulose, rice starch and 1:9 mixture of magnesium stearate and talc.

US 4,713,248 discloses coating of potassium chloride crystals using film coating mixture prepared from eudragit and methocel. The coated crystals were compressed to tablets with other excipients.

US 4,748,023 discloses sustained release tablet composition comprising potassium chloride encapsulated in ethyl cellulose, potato starch, magnesium stearate.

US 4,784,858 discloses controlled release tablet composition comprising potassium chloride coated with lower alkyl acrylate polymers.

US 4,863,743 discloses composition comprising potassium chloride crystals coated with ethylcellulose and hydroxypropyl cellulose/polyethylene glycol. The coated crystals, microcrystalline cellulose and crospovidone are mixed well and compressed in to tablets.

US 4,892,742 discloses controlled release composition containing tablet core comprising potassium chloride, ethyl cellulose, medium chain triglyceride and magnesium stearate. The tablet core is coated with film coating comprising ethyl cellulose 50 cps, hydroxypropyl methyl cellulose, stearic acid, methylene chloride and alcohol.

US 5,397,574 discloses composition comprising potassium chloride crystals coated with ethyl cellulose and Triacetin. The coated crystals along with microcrystalline cellulose and cross linked polyvinylpyrrolidone were compressed in to tablets.

US 5,422,122 discloses composition comprising ethyl cellulose encapsulated potassium chloride compressed in to tablets with microcrystalline cellulose and cross linked polyvinylpyrrolidone.

US 5,427,799 discloses sustained release composition comprising potassium chloride, xanthan gum and stearic acid.

US 5,505,962 discloses controlled release composition comprising potassium chloride, permeable component and impermeable component.

US 6,780,437 discloses composition comprising potassium chloride crystals coated with ethyl cellulose. The coated crystals were compressed along with microcrystalline cellulose and croscarmellose sodium to tablets.

US 7,632,521 discloses process for preparing controlled release tablet comprising microencapsulating potassium chloride crystals which are then coated with plasticized polymer and compressed with microcrystalline cellulose and colloidal silicon dioxide to tablets.

US 2005/0084531 discloses composition comprising tablet core containing potassium chloride, povidone (USP), FD&C Yellow #6 Lake, stearic acid powder, magnesium stearate and water. The tablets were coated with coating composition comprising eudragit, PEG, silicon dioxide, lactose anhydrous, soft talc, simethicone emulsion, FD&C yellow #6 Lake and purified water.

WO 01/43725 discloses process for preparing controlled release potassium chloride tablet comprising coating potassium chloride crystals with a first polymer coating and a second plasticized hydrophilic polymer coating, blending the coated potassium chloride crystals with microcrystalline cellulose, cross povidone and sodium lauryl sulfate and compressing the blend into a tablet.

IN 1339/CHE/2010 discloses process for preparing controlled release composition comprising potassium chloride granules prepared by wet granulation method using a non-aqueous solvent.

Balaji Guddeti etal., discloses formulation development and evaluation of potassium chloride extended release tablets in International Journal of Pharmaceutical Development and Technology 4(1), 2014, 8-20. The cited research work, focus on preparation of Potassium chloride ER tablets by using hydrophobic polymers i.e. Eudragit RSPO and Ethyl cellulose in different ratio. The granulating fluid involves Preparation of wax medium: The stearyl alcohol/ cetyl alcohol were melted at 60°C and ethanol (95%) is added, mixed properly with stainless steel spatula. The rapid drug release is rectified through the formulation development by changing the polymer ratio and the remaining issues like low hardness, high friability, lower side of assay were rectified through the process optimization by optimized the process and granulator parameters. The coating issues were rectified through the formulation development of coating formula.

The above prior arts disclose various controlled release compositions comprising potassium chloride and processes for preparation thereof. However, there are several drawbacks to adopt known processes of preparing potassium chloride controlled release compositions, for example, changing the hydrophobic polymers ratio and/or optimization of complex process steps which is time consuming and has high complexity inorder to conclude on an ideal formulation with desired drug release. Surprisingly, the inventors of the present invention have endeavored to develop simple, improved and cost effective process for preparing controlled release compositions of potassium chloride with enhanced solubility and bioavailability. Furthermore, the compositions of the present invention are safe to use and provide the desired drug release both in-vivo and in-vitro for the intended duration.

OBJECTIVE OF THE INVENTION

The objective of the present invention is to provide oral controlled release compositions comprising potassium chloride and one or more pharmaceutically acceptable excipients.

Another objective of the present invention is to provide improved, cost effective and time saving process for preparation of oral controlled release compositions comprising potassium chloride and one or more pharmaceutically acceptable excipients.

Another objective of the present invention is to provide methods of using the oral controlled release compositions comprising potassium chloride and one or more pharmaceutically acceptable excipients.

Yet another objective of the present invention is to provide oral controlled release compositions comprising potassium chloride, which exhibit comparative in-vitro dissolution profile with respect to the reference product KLORCON®, and which exhibit comparative in-vivo bioequivalence study with respect to the reference product KLORCON®.

SUMMARY OF THE INVENTION

In an embodiment, the present invention relates to an oral controlled release composition comprising potassium chloride, at least one matrix former, optionally with one or more other excipient(s).

In another embodiment, the present invention relates to an improved process for preparation of oral controlled release compositions comprising potassium chloride and one or more pharmaceutically acceptable excipients.

In yet another embodiment, the present invention provides an improved process for preparation of oral controlled release compositions comprising potassium chloride using hot melt granulation.

In another embodiment, the present invention provides an improved process for preparation of oral controlled release compositions comprising potassium chloride using hot melt granulation comprising the steps of:

(i) mixing potassium chloride and matrix former, optionally with other excipient(s), (ii) melting the mixture,

(iii) granulating the molten mixture, followed by drying.

(iv) mixing the granulated mixture of step (iii) optionally with other excipient(s), and (v) compressing the granulation mixture of step (iv) into tablets.

In yet another embodiment, the present invention provides an improved process for preparation of oral controlled release compositions comprising potassium chloride using hot melt granulation comprising the steps of:

(i) mixing potassium chloride and matrix former, optionally with other excipient(s) in fluid bed processor (FBP), (ii) melting the mixture,

(iii) granulating the molten mixture, followed by drying.

(iv) mixing the granulated mixture of step (iii) optionally with other excipient(s), and (v) compressing the granulation mixture of step (iv) into tablets.

DETAILED DESCRIPTION OF THE INVENTION

In an embodiment, the present invention relates to an oral controlled release composition comprising potassium chloride, at least one matrix former, optionally with one or more other excipient(s).

In another embodiment, the present invention relates to oral controlled release compositions comprising potassium chloride, matrix forming agent for controlling the release of the drug and one or more pharmaceutically acceptable excipients.

In another embodiment, the present invention relates to an improved process for preparation of oral controlled release compositions comprising potassium chloride and one or more pharmaceutically acceptable excipients.

In another embodiment, the present invention provides an improved process for preparation of oral controlled release compositions comprising potassium chloride and one or more pharmaceutically acceptable excipients using hot melt granulation.

In another embodiment, the present invention provides an improved process for preparation of oral controlled release compositions comprising potassium chloride using hot melt granulation comprising the steps of:

(i) mixing potassium chloride and matrix former, optionally with other excipient(s), (ii) melting the mixture,

(iii) granulating the molten mixture, followed by drying.

(iv) mixing the granulated mixture of step (iii) optionally with other excipient(s), and (v) compressing the granulated mixture of step (iv) into tablets, (vi) optionally coating the tablets obtained in step (v).

In yet another embodiment, the present invention provides an improved process for preparation of oral controlled release compositions comprising potassium chloride using hot melt granulation comprising the steps of:

(i) mixing potassium chloride and matrix former, optionally with other excipient(s) in fluid bed processor (FBP), (ii) melting the mixture,

(iii) granulating the molten mixture, followed by drying.

(iv) mixing the granulated mixture of step (iii) optionally with other excipient(s), and (v) compressing the granulated mixture of step (iv) into tablets.

The term "composition" or "formulation" or "dosage form" or "medicinal preparation" as used multiunit particulate herein synonymously include solid dosage forms such as granules, systems (MUPS), pellets, spheres, tablets, capsules, mini-tablets, beads, crystals, particles and the like meant for oral administration.

As used in this specification, the singular forms "a", "an" and "the" include plural references unless the; context clearly dictates otherwise. Thus for example, a reference to "a process" includes one or more processes, and/or steps of the type described herein and/or which will become apparent to those persons skilled in the art.

The term "excipient" means a pharmacologically inactive component such as a diluent, disintegrant, carrier and the like. The excipients that are useful in preparing a pharmaceutical composition are generally safe, non-toxic and are acceptable for human as well as veterinary pharmaceutical use. Reference to an excipient includes both one and more than one such excipient.

The term "particle size" unless indicated otherwise in the specification relates to particles of potassium chloride thereof with specific "particle size" and distribution, or surface area would provide a faster dissolution of the active ingredient, would be easy to prepare and stable while maintaining the beneficial properties with respect to solubility and bioavailability.

An embodiment of the present invention relates to oral controlled release composition comprising potassium chloride and one or more pharmaceutical^ acceptable excipients, wherein the ratio of potassium chloride to excipients is in the range of 1:1 to 1:200.

In an embodiment, the composition comprises potassium chloride with a particle size d90 of about 40 microns to 900 microns, or about 100 microns to about 600 microns, or about 350 microns to about 500 microns.

The term "pharmaceutical acceptable excipient" as used herein refers to additives useful for converting pharmacologically active compounds into pharmaceutical dosage forms which are suitable for administration to patients. Suitable excipients include diluents, binders, matrix forming agents, wicking agents, lubricants, glidants, film forming polymers, plasticizers and coloring agents. Other pharmaceutically acceptable excipients can also be included.

Suitable "diluents" used according to the present invention include but are not limited to water soluble or water insoluble diluents comprising sucrose, dextrose, lactose, mannitol, sorbitol, starch, microcrystallihe cellulose, silicified microcrystalline cellulose, calcium silicate arid the like or combination thereof. The amount of diluent may range from about 5 % to 95 % by weight of the composition.

Binders according to the present invention refer to polymers which provide binding effect as well as release retarding effect. The binders having melting point below 130°C, preferably below 100°C are selected from the group of polyethylene glycols with molecular weights of 1500 to 20000 such as PEG 4000, PEG 6000; poloxamers with molecular weights in the range 5000 to 20000 such as Poloxamer 188, Poloxamer 237, Poloxamer 338 or Poloxamer 407 commercially available as Lutrol® or Pluronic® types; Cg-Cig fatty acid esters of polyoxylglicerides of Gelucire® type; Cs-Cis fatty acid esters of polyethylene glycol; sugar esters such as sucrose stearate, sucrose palmitate or sucrose laurate or glyceryl behenate and the like. The amount of binder may range from 0 % to about 20 % by weight of the composition.

Matrix systems are widely used for the purpose of controlling the release of an agent. It is the release system which prolongs and controls the release of the drug that is dissolved or dispersed. In fact, a matrix is defined as a well-mixed composite of one or more drugs with gelling agent i.e. hydrophilic or hydrophobic polymers. Suitable matrix forming agents include but are not limited to hydrogenated vegetable oil, hydroxypropylmethyl cellulose, polylactic acid, povidone, sucrose stearate ester, sucrose palmitate ester, xanthan gum, polyethylene oxide, sodium alginate, polyvinyl chloride, polyglycolic acid, chitosan and modified starches. The amount of matrix forming agent may range from about 1 % to 80 % by weight of the composition.

Suitable "lubricants" used according to the present invention include but are not limited to magnesium stearate, hydrogenated castor oil, calcium stearate, sodium stearyl fumarate, talc, vegetable oils, stearic acid, fumaric acid and the like. More preferably the lubricant used is magnesium stearate. The amount of lubricants may range from about 0.1% to about 6 % by weight of composition.

Suitable "wicking agents" used according to the present invention include but are not limited to colloidal silicon dioxide, magnesium aluminum silicate, microcrystalline cellulose, titanium dioxide, polyester, polyethylene and alumina. The amount of wicking agent may range from about 0.1 % to 45 % by weight of the composition.

In an embodiment, the composition is prepared by an improved hot melt granulation process. The process can be carried out in high shear mixers or granulators, fluid bed granulators or fluid bed processors. More preferably the process is carried out in fluid bed processor.

In another embodiment, the present invention provides an improved process for preparation of oral controlled release compositions comprising potassium chloride, matrix former and one or more other pharmaceutically acceptable excipients using hot melt granulation.

In another embodiment, the present invention provides an improved process for preparation of oral controlled release compositions comprising potassium chloride, matrix former and one or more other pharmaceutically acceptable excipients using hot melt granulation carried out in fluid bed processor.

In another embodiment, the present invention provides an improved process for preparation of oral controlled release compositions comprising potassium chloride, matrix former selected from hydrogenated vegetable oil or povidone and one or more other pharmaceutically acceptable excipients selected from the group consisting of glidants, lubricants and film forming polymers using hot melt granulation.

In another embodiment, the present invention provides an improved process for preparing oral controlled release composition comprising potassium chloride comprising the steps of:

(i) mixing potassium chloride, matrix former and optionally other excipient(s), (ii) melting the mixture,

(iii) granulating the molten mixture, followed by drying.

(iv) mixing the granulated mixture of step (iii) with glidant and optionally with other excipient(s),

(v) compressing the granulated mixture of step (iv) in to tablets, and (vi) coating the tablets of step (v).

In yet another embodiment, the present invention provides an improved process for preparing oral controlled release composition comprising potassium chloride comprising the steps of:

(i) mixing potassium chloride, matrix former which is hydrogenated vegetable oil, and optionally other excipient(s) selected from diluents and disintegrants, in fluid bed processor, (ii) melting the mixture,

(iii) granulating the molten mixture, followed by drying.

(iv) mixing the granulated mixture of step (iii) with glidant such as colloidal silicon dioxide and optionally with other excipient(s) selected from wicking agents and lubricants,

(v) compressing the granulated mixture of step (iv) in to tablets, and

(vi) coating the tablets of step (v).

The specific melting conditions depend on the melting range of compounds or excipients used to make the formulation. Accordingly in the present invention, the melting temperatures from about 35° C to 200° C or from about 50° C to 160° C or from about 50° C to 80° C are used.

In an embodiment, the granulation is carried out in fluid bed processor either in molten state or after having cooled to room temperature.

In an embodiment, the resulting granulation composition comprises a particle size d90 of about 200 microns to 1200 microns, or about 400 microns to 1000 microns, or about 700 microns to 900 microns.

In another embodiment of the present invention, the solid dosage forms include tablets, pellets, beads and capsules. The tablets may be uncoated or optionally coated.

In yet another embodiment of the present invention, film coating composition comprises a solution/suspension of film coating polymers and one or more excipients such as glidants, plasticizers, opacifying agents and colorants.

Suitable "film coating polymers" used according to the present invention include but are not limited to povidone, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethyl cellulose, polyvinyl alcohol and the like or mixtures thereof. The amount of film coating polymer may range from about 1% to 5% by weight of composition.

The inclusion of a plasticizer in the polymer dispersion improves the physical properties of the film. Suitable plasticizers according to the present invention include but are not limited to polyethylene glycol, propylene glycol, diethyl phthalate, castor oil, triethyl citrate, tributyl citrate and dibutyl sebacate. The amount of plasticizer may range from about 5 % to 30 % by weight of the composition.

Suitable glidants according to the present invention include but are not limited to talc, colloidal silicon dioxide, dibasic calcium phosphate, tribasic calcium phosphate and pregelatinized starch. The amount of glidant may range from about 0.1 % to 8% by weight of the composition.

Opacifying agents provide film coatings with excellent brightness, whiteness, and/or opacity without using compounds containing heavy metals. Suitable opacifying agents according to the present invention include but are not limited to clays and divalent salts such as zinc oxides, dicalcium phosphate, dicalcium phosphate dehydrate, tricalcium phosphate, calcium carbonate, titanium dioxide and precipitated calcium carbonate. The amount of opacifying agent may range from about 0.5%. to 65% or 25% to 50% by weight of the film coating composition.

Suitable coloring agents according to the present invention include dyes, lakes, and pigments and may include, but are not limited to titanium dioxide, iron oxides, dyes such as, for example, FD&C Lakes, Carmine Lake, FD&C Blue no. 1, FD&C Blue no, 2, FD&C Red no. 3, FD&C Red no. 40, FD&C Yellow no. 5, FD&C Yellow no. 6, FD&C Green no. 3, erythrosine, iron oxide red and iron oxide black.

In another embodiment, the present invention provides the use of oral controlled release compositions comprising potassium chloride for the prophylaxis and/or treatment of hypokalemia with or without metabolic alkalosis.

The following examples further illustrate the invention and are not intended to limit the scope of the invention. It is obvious to those skilled in the art to find out the composition for other dosage forms and substitute the equivalent excipients as described in this specification or with the one known to the industry.

Examples 1 and 2:

* Opadry Yellow consists of polyvinyl alcohol, polyethylene glycol, talc, titanium dioxide, D&C Yellow #10 Aluminium lake, FD&C Yellow #6 Aluminium lake.

Qs - Quantity sufficient.

The process involved in manufacturing oral controlled release compositions given in

Examples 1 to 8 comprises the following steps:

(i) Potassium chloride and hydrogenated vegetable oil or povidone were sifted through 420 urn mesh and mixed in fluid bed processor.

(ii) Fluid bed processor was heated to 60±10°C.

(iii) The granules of step (ii) were sifted through 850 urn mesh.

(iv) Colloidal silicon dioxide or microcrystalline cellulose was sifted through 420 um mesh and blended with granules of step (iii).

(v) The granules of step (iv) were lubricated with magnesium stearate.

(vi) The lubricated granules of step (v) were compressed to tablets.

(vii) Coating dispersion was prepared by dispersing Opadry® in water.

(viii) The compressed tablets obtained in step (vi) were subjected to coating using dispersion of step (vii).

The dissolution profile of controlled release tablets of potassium chloride prepared according to the present invention were carried out in 900 ml of purified water, Apparatus USP II, Paddle, 50 rpm. The release profile (% of drug dissolved vs time) is given in table 1.

Claims:

1. An oral controlled release composition comprising potassium chloride, at least one matrix former, optionally with one or more other excipient(s), wherein the said composition is prepared by an improved hot melt granulation process.

2. The improved hot melt granulation process for the preparation of oral controlled release composition according to claim 1, which comprises of the following steps:

(i) mixing potassium chloride and at least one matrix former, optionally with one or more other excipient(s),

(ii) melting the mixture of step (i) and granulating the molten mixture, followed by drying.

(iii) optionally sifting the dried granules of step (ii),

(iv) mixing the granules of step (ii) or (iii) with other excipient(s),

(v) compressing the granules of step (iv) into tablets, and

(vi) optionally coating the tablets obtained in step (v).

3. The improved process according to claim 2, wherein the process steps (i) and (ii) are carried out in high shear granulator or fluid bed granulator.

4. The composition according to claim 1, wherein the matrix former is selected from a group comprising hydrogenated vegetable oil, hydroxypropylmethyl cellulose, polylactic acid, povidone, sucrose stearate ester, sucrose palmitate ester, xanthan gum, polyethylene oxide, sodium alginate, polyvinyl chloride, polyglycolic acid, chitosan, modified starches, and mixtures thereof, and wherein the said composition is prepared by the improved hot melt granulation process as described in claim 2.

5. The composition according to claim 1, wherein the one or more other excipient(s) are selected from a group comprising diluents, binders, matrix forming agents, wicking agents, lubricants, glidants, film forming polymers, plasticizers, coloring agents, and combinations thereof, and wherein the said composition is prepared by the improved hot melt granulation process as described in claim 2.

6. The composition according to claim 5, wherein the binder is selected from a group comprising polyethylene glycols with molecular weights of 1500 to 20000; poloxamers with molecular weights in the range 5000 to 20000; C8-Ci8 fatty acid esters of polyoxylglicerides; Cg-Cig fatty acid esters of polyethylene glycol; sugar esters, and mixtures thereof, and wherein the said composition is prepared by the improved hot melt granulation process as described in claim 2.

7. The composition according to claim 5, wherein the diluent is selected from a group comprising sucrose, dextrose, lactose, mannitol, sorbitol, starch, microcrystalline cellulose, calcium silicate, and mixtures thereof, and wherein the said composition is prepared by the improved hot melt granulation process as described in claim 2.

8. The composition according to claim 5, wherein the lubricant is selected from a group comprising magnesium stearate, hydrogenated castor oil, calcium stearate, talc, vegetable oils, stearic acid, fumaric acid, and mixtures thereof, and wherein the said composition is prepared by the improved hot melt granulation process as described in claim 2.

9. The composition according to claim 5, wherein the glidant is selected from a group comprising talc, colloidal silicon dioxide, dibasic calcium phosphate, tribasic calcium phosphate, pregelatinized starch and mixtures thereof, and wherein the said composition is prepared by the improved hot melt granulation process as described in claim 2.

10. The oral controlled release composition of potassium chloride according to claim 1 prepared by the improved hot melt granulation process as described in claim 2, which is useful for the prophylaxis and/or treatment of hypokalemia with or without metabolic alkalosis.