WO2025177113A1

WO2025177113A1 - An orodispersible tablet of spironolactone and its process of preparation

Info

Publication number: WO2025177113A1
Application number: PCT/IB2025/051309
Authority: WO
Inventors: Kamleshkumar Patel
Original assignee: Novumgen Ltd
Current assignee: Novumgen Ltd
Priority date: 2024-02-21
Filing date: 2025-02-07
Publication date: 2025-08-28
Anticipated expiration: 2026-08-21
Also published as: GB2638418A

Abstract

The present invention relates to an orodispersible tablet comprising spironolactone or pharmaceutically acceptable salts thereof, at least one diluent, a disintegrant, a binder, a solubilizer, a lubricant, and one or more pharmaceutically acceptable excipients. The orodispersible tablet of spironolactone or pharmaceutically acceptable salts thereof is formulated for acceptable palatability and taste-masking of the bitter drug, thereby enhancing patient compliance, especially among pediatric and geriatric individuals with dysphagia. The orodispersible tablet of spironolactone is manufactured by the wet granulation method to provide a faster disintegration and dissolution rate of said tablet.

Description

An Orodispersible tablet of Spironolactone and its process of preparation.

Field of the Invention

The present invention relates to a pharmaceutical composition of Spironolactone. The present invention relates to an orodispersible tablet of Spironolactone or pharmaceutically acceptable salts thereof for oral administration. The present invention also relates to the process of the preparation of the same. of the Invention

Spironolactone was first disclosed in the US3013012A. Spironolactone and its active metabolites are aldosterone antagonists that produce a potassium-sparing diuretic effect. They competitively bind to receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted while potassium is retained. Spironolactone acts both as a diuretic and as an antihypertensive drug by this mechanism.

Spironolactone is indicated for the treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure. Spironolactone is usually administered in conjunction with other heart failure therapies, hypertension, as add-on therapy, in patients not adequately controlled by other agents, edema associated with hepatic cirrhosis, edema associated with nephrotic syndrome when treatment of the underlying disease, restriction of fluid and sodium intake, and the use of other diuretics produce an inadequate response, refractory edema associated with congestive cardiac failure, malignant ascites, hepatic cirrhosis with ascites, and essential hypertension, short-term preoperative treatment of patients with primary hyperaldosteronism, long-term maintenance therapy for patients with discrete aldosterone-producing adrenal adenomas who are not candidates for surgery, longterm maintenance therapy for patients with bilateral micro or macro nodular adrenal hyperplasia. The IUPAC name of Spironolactone is S-[(7R,8R,9S,10R,13S,14S,17R)- 10,13 dimethyl-3,5'-dioxospiro [2,6,7,8,9,11,12,14,15,16- decahydro-lH cyclopenta [a]phenanthrene-17,2'-oxolane]-7-yl] ethane thioate. The plasma half-life of spironolactone is 1.4 hours. Spironolactone is a low-solubility, high-permeability drug which makes it belong to BCS Class-II in the Biopharmaceutical classification system.

Spironolactone is commercially available in two dosage forms: film-coated tablets and oral suspension. The tablet of spironolactone is available in three dose strengths: 25mg, 50mg, and lOOmg. The oral suspension is available in one dose strength: 5mg/ml.

US20130203719A1 discloses tablets or capsules of spironolactone which suppresses activity at aldosterone receptors in a mammalian body. The oral solid dosage form of spironolactone is administered for suppressing aldosterone- mediated myocardial fibrosis without increasing sodium excretion and without reducing potassium retention by the body.

CN105832680A discloses tablet of spironolactone. The pharmaceutical composition manufactured by a hot-melt extrusion technique is solid dispersion, the spironolactone is dispersed into the carrier in a molecular or amorphous mode, and therefore the in-vitro dissolution of the spironolactone is significantly improved.

The marketed tablet of spironolactone presents many challenges for paediatric and geriatric patients who often experience difficulty in swallowing (Dysphagia), bitter taste and divided dose regimen resulting in patient incompliance. The oral liquid dosage form of spironolactone available in the market need to be re-dispersed before use, this can lead to issues such as inaccurate dosing measurements and administration of incorrect volume of oral suspension. Therefore, an orodispersible tablet of spironolactone is formulated in the present invention for achieving good patient compliance, accurate dose administration, and good palatability for paediatrics, geriatrics and bed-ridden patients and improved taste-masking.

Summary of the Invention

In accordance with the present invention, an orodispersible tablet of spironolactone for oral administration is prepared. The orodispersible tablet comprising spironolactone or pharmaceutically acceptable salts thereof, at least one diluent, at least one disintegrant, a binder, a solubilising agent, a lubricant, and one or more pharmaceutically acceptable excipients.

Another embodiment of the present invention provides the orodispersible tablet containing spironolactone or pharmaceutically acceptable salt thereof, which is a good drug candidate for formulating orodispersible tablet that can provide good palatability and taste-masking properties for improving patient compliance.

Further, another embodiment of the present invention is to provide a process for the preparation of an orodispersible tablet of pregabalin preferably a wet granulation method.

Another embodiment of the present invention can effectively treat NYHA Class III- IV heart failure, edema associated with hepatic cirrhosis, edema associated with nephrotic syndrome, refractory edema associated with congestive cardiac failure, malignant ascites, hepatic cirrhosis with ascites, essential hypertension, primary hyperaldosteronism, aldosterone-producing adrenal adenomas and idiopathic hyperaldosteroni sm . Objects of the Invention

The principal object of the present invention is to provide an orodispersible tablet of spironolactone or pharmaceutically acceptable salts thereof.

It is an object of the present invention to provide an orodispersible tablet, which is particularly convenient for administration to paediatrics and geriatrics and acceptable palatability for patients with swallowing difficulties and taste-masking of the bitter drug.

It is further object of the present invention to provide a process of preparation of an orodispersible tablet of spironolactone or its pharmaceutically acceptable salts thereof.

It is further another object of the present invention to enhance the disintegration and dissolution of the drug for oral administration.

Detailed description of the Invention

The present invention can be more fully understood by reading the subsequent detailed description and examples with references.

The term “orodispersible” refers to solid unit dosage forms, of the present invention, composed of super disintegrants, which help them to dissolve the tablets within a minute in the mouth in the presence of saliva without any difficulty of swallowing.

As used herein and in the appended claims, the singular forms "a", "an", and "the" include plural reference unless the context clearly dictates otherwise.

The main embodiment of the present invention is an orodispersible tablet comprised of spironolactone or pharmaceutically acceptable salts thereof, at least one diluent, a disintegrant, a binder, and a solubilizing agent. In addition, the orodispersible tablet further comprises at least one pharmaceutically acceptable excipient selected from a lubricant, glidant, sweetener, and flavour.

As per one embodiment of the present invention, spironolactone or pharmaceutically acceptable salts thereof, is present in the range from about 10%w/w to about 30%w/w, preferably in the range from about 15%w/w to about 25%w/w.

The term "about", as and when used in this specification, means ±10 % of the mentioned value.

As per one embodiment of the present invention, the composition comprises a diluent selected from the group consisting of directly compressed starch, hydrolyzed starch, microcrystalline cellulose, Dibasic calcium phosphate dehydrate, dextrose, partially pregelatinized starches, calcium sulphate dehydrates, mannitol, sorbitol, maize starch or any combinations thereof. In the present invention, the diluent is microcrystalline cellulose present in the range from about 30%w/w to about 60%w/w, preferably in the range from about 40%w/w to about 50%w/w. Maize starch is present in the range from about 10%w/w to about 40%w/w, preferably in the range from about 15%w/w to about 35%w/w. As per one preferred embodiment, the combination of microcrystalline cellulose and maize starch present in the range from about 40%w/w to about 80%w/w, preferably in the range from about 55%w/w to about 75%w/w and the composition is free from lactose.

As per one more embodiment of the present invention, the disintegrant is selected from the group consisting of starch derivative, Sodium carboxymethyl starch, clays, alginate, crospovidone, cross-linked polyvinylpyrrolidone, croscarmellose sodium, soy polysaccharide, cross-linked alginic acid, gellan gum, calcium silicate, sodium starch glycolate or any combinations thereof. In the present invention, Crospovidone is preferred as a disintegrant in the range from about 0.5 %w/w to about 15 %w/w, preferably in the range from about 1 %w/w to about 10%w/w. Crospovidone act by a wicking mechanism; drawing water into the tablet through capillary action due to its porous particle morphology, resulting in secondary swelling and rupture of interparticulate bonds and in tablet disintegration.

As per one embodiment of the present invention, the ratio of combination of diluents to disintegrant is in the range from about 1 : 1 to about 20: 1, preferably in the range from about 5: 1 to 15: 1. As per one preferred embodiment of the present invention, the ratio of combination of maize starch and microcrystalline cellulose to crospovidone is in the range from about 1 : 1 to about 20: 1, preferably in the range from about 5 : 1 to about 15: 1.

As per one embodiment of the present invention, a suitable binder is selected from the group consisting of acacia, starch, tragacanth, methylcellulose, cellulose derivatives, gelatin, Polyethylene glycol, glucose, polyvinylpyrrolidone, starch paste, sodium alginate, sorbitol, povidone or any combinations thereof. In the present invention, povidone is preferred as a binder in the range from about l%w/w to about 10%w/w, preferably in the range from about 2%w/w to about 8%w/w.

As per one embodiment of the present invention, a solubilizing agent is selected from the group consisting of egg yolk lecithin, gum arabic, hydrogenated castor oil, dipolyhydroxy stearate, hydrated Silica, polysorbate, polyoxyl hydrogenated castor oil, sodium deoxycholate, hydroxypropyl methylcellulose, soya lecithin or any combinations thereof. In the present invention, polysorbate is preferred as solubilizing agent present in the range from about 0.01%w/w to about 1 %w/w, preferably in the range from about 0.05 %w/w to about 0.5%w/w.

As per one another embodiment of the present invention, a lubricant selected from the group consisting of boric acid, magnesium stearate, sodium stearyl fumarate, micronized polyoxy ethylene glycol, leucine, sodium benzoate, sodium acetate, sodium lauryl sulfate, stearic acid, sodium stearate, sodium oleate, calcium stearate, waxes or combinations thereof. In the present invention, magnesium stearate is preferred as a lubricant is present in the range from about 0.1 %w/w to about 8%w/w, preferably in the range from about 0.5 %w/w to about 5%w/w.

As per one embodiment of the present invention, the glidant is selected from the group consisting of ascorbyl palmitate, calcium palmitate, magnesium stearate, colloidal anhydrous silica, starch, talc or any combinations thereof. In the present invention, colloidal anhydrous silica is preferred as a glidant in the range from about 0.1 %w/w to about 8%w/w, preferably in the range from about 0.5%w/w to about 5%w/w.

As per one more embodiment of the present invention, a sweetener is selected from the group consisting of cyclamate, acesulfame potassium, neo hesperidin dihydrochalcone, monoammonium glycyrrhizinate, saccharin sodium, sucralose, saccharin, aspartame or any combinations thereof. In the present invention, sodium saccharin is preferred as a sweetener in the range from about 0.05%w/w to about 3.5%w/w, preferably in the range from about 0.1%w/w to about l%w/w.

As per one embodiment of the present invention, a flavor is selected from the group consisting of peppermint flavor, cooling flavor, flavor oils and flavoring aromatic oil, peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil, thyme oil, oil of bitter almonds, vanilla, citrus oils, fruit essences or any combinations thereof. In the present invention, peppermint flavor is present in the range from about 0.05 %w/w to about 3.5%w/w, preferably in the range from about 0.1%w/w to about 1 %w/w.

As per the preferred embodiment, an orodispersible tablet of spironolactone is used in the treatment of NYHA Class III-IV heart failure, edema associated with hepatic cirrhosis, edema associated with nephrotic syndrome, refractory edema associated with congestive cardiac failure, malignant ascites, hepatic cirrhosis with ascites, essential hypertension, primary hyperaldosteronism, aldosterone-producing adrenal adenomas, and idiopathic hyperaldosteronism. As per one embodiment of the present invention, an orodispersible tablet comprising spironolactone or pharmaceutically acceptable salts thereof, present in an amount from about 10%w/w to about 30%w/w, preferably in the range from about 15%w/w to about 25%w/w, a combination of diluents present in the range from about 40%w/w to about 80%w/w, preferably in the range from about 55%w/w to about 75%w/w, a disintegrant in the range from about 0.5 %w/w to about 15 %w/w, preferably in the range from about l%w/w to about 10 %w/w, a binder in the range from about l%w/w to about 10%w/w, preferably in the range from about 2%w/w to about 8%w/w, a solubilizing agent present in the range from about 0.01%w/w to about 1 %w/w, preferably in the range from about 0.05%w/w to about 0.5%w/w, a lubricant is present in the range from about 0. l%w/w to about 8%w/w, preferably in the range from about 0.5%w/w to about 5%w/w, a glidant in the range from about 0.1 %w/w to about 8%w/w, preferably in the range from about 0.5%w/w to about 5%w/w, a sweetener in the range from about 0.05%w/w to about 3.5%w/w, preferably in the range from about 0.1%w/w to about l%w/w, a flavor is present in the range from about 0.05%w/w to about 3.5%w/w, preferably in the range from about 0. l%w/w to about l%w/w.

As per preferred embodiment of the present invention, an orodispersible tablet comprising spironolactone or pharmaceutically acceptable salts thereof, present in an amount from about 10%w/w to about 30%w/w, preferably in the range from about 15%w/w to about 25%w/w, a combination of microcrystalline cellulose and maize starch present in the range from about 40%w/w to about 80%w/w, preferably in the range from about 55%w/w to about 75%w/w, crospovidone is present in the range from about 0.5 %w/w to about 15 %w/w, preferably in the range from about 1 %w/w to about 10 %w/w, povidone is present in the range from about l%w/w to about 10%w/w, preferably in the range from about 2%w/w to about 8%w/w, polysorbate is present in the range from about 0.01%w/w to about l%w/w, preferably in the range from about 0.05%w/w to about 0.5%w/w, magnesium stearate is present in the range from about 0.1 %w/w to about 8%w/w, preferably in the range from about 0.5%w/w to about 5%w/w, colloidal anhydrous silica is present in the range from about 0.1 %w/w to about 8 %w/w, preferably in the range from about 0.5 %w/w to about 5%w/w, sodium saccharin is present in the range from about 0.05%w/w to about 3.5%w/w, preferably in the range from about 0.1%w/w to about 1 %w/w, peppermint flavor is present in the range from about 0.05 %w/w to about 3.5%w/w, preferably in the range from about 0.1 %w/w to about 1 %w/w.

As per one embodiment of the present invention, an orodispersible tablet comprising spironolactone or pharmaceutically acceptable salts thereof is manufactured by wet granulation.

As per one embodiment of the present invention, the disintegrating time of the spironolactone orodispersible tablet is not more than 3 minutes, preferably less than 2 minutes.

As per one embodiment of the present invention, 90% of the spironolactone is released in 60 minutes, preferably more than 90% is released within 45 minutes.

As per one embodiment of the present invention, the stability study of orodispersible tablet of spironolactone was carried out by placing tablets in PVC and PVDC blister packs and HDPE bottles with CR cap containing silica gel and stored at 25°C/60%RH and 40°C/75%RH for 3 months. The orodispersible tablets of spironolactone were stable in blister and bottle as the said packaging conditions delivered good physicochemical parameters in stability studies.

As per one more embodiment of the present invention, the wet granulation method is used to manufacture the orodispersible tablet of spironolactone. Spironolactone, microcrystalline cellulose, maize starch, crospovidone, colloidal anhydrous silica, sodium saccharin, and peppermint flavor through a 40# sieve and magnesium stearate were sieved through a 60# sieve. A binder solution was prepared by dissolving povidone in 50% of the total amount of purified water with continuous stirring until a clear viscous solution was achieved. To this solution, polysorbate was mixed under continuous stirring until a clear viscous solution was achieved. Spironolactone, microcrystalline cellulose, maize starch, and crospovidone were dry mixed in a rapid mixer granulator for 15 minutes. To the rapid mixture granulator, previously prepared binder solution was added with continuous mixing at slow speed with intermittent addition of the remaining quantity of purified water. The wet mass thus obtained was raked off from the rapid mixture granulator into a fluid bed drier bowl. The granules were dried in a fluidized bed dryer with an inlet temperature of 50°C±5°C. The granules were first sieved through 24# and retained granules were milled through a mill screen 1.5 mm and all the blend was passed through a 24# sieve. To this final mixture, previously sifted crospovidone, sodium saccharin, colloidal anhydrous silica, and peppermint flavour were added to the blender for 15 minutes. Magnesium stearate previously sifted was blended in the blender for 5 minutes. The final mixture was compressed into tablets. The stability study of orodispersible tablet of spironolactone was carried out by placing tablets in PVC and PVDC blister pack and HDPE bottles with CR cap containing silica gel and stored at 25°C/60%RH and 40°C/75% RH for 3 months. The orodispersible tablets of spironolactone were stable in blister and bottle as the said packaging conditions delivered good physicochemical parameters in stability studies.

The invention is further illustrated by the following examples, which are by no means intended to limit the scope of the invention but are given by way of illustration.

Example 1:

The Orodispersible Tablet was made according to the method defined below using the formulation having the ingredients shown in Table-I for dose strengths that are 25mg of spironolactone: TABLE-I

Manufacturing process:

Spironolactone, microcrystalline cellulose, maize starch, Crospovidone, colloidal anhydrous silica, sodium saccharin, and peppermint flavor were sieved separately through 40# sieve and magnesium stearate were sieved separately through 60# sieve. Spironolactone, microcrystalline cellulose, and maize starch were mixed in a blender for 15 minutes. To this resulting mixture, the blend mixture of crospovidone, sodium saccharin, colloidal anhydrous silica, and peppermint flavor was added. To this final mixture, previously sifted magnesium stearate was added and mixed for 5 minutes.

The physical parameter of the blend was not satisfactory; the blend flow was poor.

In order to optimize the blend flow, it was necessary to change the manufacturing process from dry granulation to wet granulation. Example 2:

The Orodispersible Tablet was made according to the method defined below using the formulation having the ingredients shown in Table-II for dose strengths that are 25mg of spironolactone: TABLE-II

Manufacturing process:

Spironolactone, microcrystalline cellulose, maize starch, crospovidone, colloidal anhydrous silica, sodium saccharin, and peppermint flavor were sieved separately through a 40# sieve and magnesium stearate were sieved through a 60# sieve. A binder solution was prepared by dissolving povidone in 50% of the total amount of purified water with continuous stirring until a clear viscous solution was achieved. To this solution, polysorbate was mixed under continuous stirring until a clear viscous solution was achieved. Spironolactone, microcrystalline cellulose, maize starch, and Crospovidone were dry mixed in a rapid mixer granulator for 15 minutes. To the rapid mixture granulator, previously prepared binder solution was added with continuous mixing at slow speed with intermittent addition of the remaining quantity of purified water. The wet mass thus obtained was raked off from the rapid mixture granulator into a fluid bed drier bowl. The granules were dried in a fluidized bed dryer with an inlet temperature of 50°C±5°C. The granules were first sieved through 24# and retained granules were milled through a mill screen 1.5 mm and all the blend was passed through a 24# sieve. To this final mixture, previously sifted sodium saccharin, colloidal anhydrous silica, and peppermint flavor were added to the blender for 15 minutes. Magnesium stearate previously sifted was blended in the blender for 5 minutes.

The physical parameter of the blend was not satisfactory. Disintegration time is more than 3 min, in order to optimize the disintegration time, it was necessary to increase the concentration of disintegrant

Example 3:

The Orodispersible Tablet was made according to the method defined below using the formulation having the ingredients shown in Table-Ill for dose strengths that are 25mg of spironolactone:

Table -III

Manufacturing process:

Spironolactone, microcrystalline cellulose, maize starch, Crospovidone, colloidal anhydrous silica, sodium saccharin, and peppermint flavor through a 40# sieve and magnesium stearate were sieved through a 60# sieve. A binder solution was prepared by dissolving Povidone in 50% of the total amount of purified water with continuous stirring until a clear viscous solution was achieved. To this solution, polysorbate was mixed under continuous stirring until a clear viscous solution was achieved. Spironolactone, microcrystalline cellulose, maize starch, and Crospovidone were dry mixed in a rapid mixer granulator for 15 minutes. To the rapid mixture granulator, previously prepared binder solution was added with continuous mixing at slow speed with intermittent addition of the remaining quantity of purified water. The wet mass thus obtained was raked off from the rapid mixture granulator into a fluid bed drier bowl. The granules were dried in a fluidized bed dryer with an inlet temperature of 50°C±5°C. The granules were first sieved through 24# and retained granules were milled through a mill screen 1.5 mm and all the blend was passed through a 24# sieve. To this final mixture, previously sifted Crospovidone, sodium saccharin, colloidal anhydrous silica, and peppermint flavour were added to the blender for 15 minutes. Magnesium stearate previously sifted was mixed in a blender for 5 minutes. All the physical and chemical parameters of the tablets were found satisfactory.

Example 4: The Dissolution profile of the tablet prepared according to Example 3.

The conditions of dissolution are as follows:

Product Name: Spironolactone 25 mg Orodispersible tablet

Media : 0.1N HCL+ 0.1% SLS

Apparatus & RPM: Apparatus II (Paddle) Rate of rotation: 75 RPM

Volume: 1000 ml

Temperature: 37°C The orodispersible tablet of spironolactone was analyzed for its dissolution profile measured in 500 ml of 0.1N HCL+ 0.1% SLS at 75 RPM in USP II (Paddle) apparatus and the active ingredient of the tablet was released is more than 90% in 45 minutes.

Example 5:

The orodispersible tablet prepared according to example 3 was subjected to a stability study of 25°C/60%RH and 40°C/75%RH and results are tabulated below for dose strengths 25mg of spironolactone in blister and bottle: Stability Data: Spironolactone 25mg orodispersible Tablet - Exp-3 (Bottle) Stability Data: Spironolactone 25mg Orodispersible Tablet - Exp-3 (Blister)

Claims

Claims:

1. An orodispersible tablet of Spironolactone for oral administration comprising: a) Spironolactone or pharmaceutically acceptable salts thereof, is present in an amount ranging from about 10%w/w to about 30%w/w, preferably in the range from about 15%w/w to about 25%w/w; b) at least one diluent; and c) at least one or more pharmaceutically acceptable excipients, wherein the Orodispersible tablet is disintegrated upon contact with saliva in less than 3 minutes, preferably less than 2 minutes.

2. The orodispersible tablet according to claim 1 , wherein the diluent is selected from the group consisting of directly compressed starch, hydrolyzed starch, microcrystalline cellulose, dibasic calcium phosphate dehydrate, dextrose, partially pregelatinized starches, calcium sulphate dehydrates, mannitol, sorbitol, maize starch or any combinations thereof.

3. The orodispersible tablet according to claim 2, wherein the diluent is the combination of microcrystalline cellulose and maize starch present in the range from about 40%w/w to about 80%w/w, preferably in the range from about 55%w/w to about 75%w/w.

4. The orodispersible tablet according to claim 2, wherein the diluent is microcrystalline cellulose present in the range from about 30%w/w to about 60%w/w, preferably in the range from about 40%w/w to about 50%w/w.

5. The orodispersible tablet according to claim 2, wherein the diluent is maize starch present in the range from about 10%w/w to about 40%w/w, preferably in the range from about 15%w/w to about 35%w/w.

6. The orodispersible tablet according to claim 2, wherein the composition is free from lactose.

7. The orodispersible tablet according to claim 1, wherein the disintegrant is selected from the group consisting of starch derivative, Sodium carboxymethyl starch, clays, alginate, crospovidone, cross-linked polyvinylpyrrolidone, croscarmellose sodium, soy polysaccharide, cross-linked alginic acid, gellan gum, calcium silicate, sodium starch glycolate or any combinations thereof.

8. The orodispersible tablet according to claim 7, wherein the disintegrant is crospovidone present in the range from about 0.5 %w/w to about 15 %w/w, preferably in the range from about 1 %w/w to about 10 %w/w.

9. The orodispersible tablet according to claim 1 , wherein the ratio of the combination of diluents to disintegrant is in the range from about 1 : 1 to about 20: 1, preferably in the range from about 5:1 to about 15:1.

10. The orodispersible tablet according to claim 9, wherein the ratio of the combination of maize starch and microcrystalline cellulose to crospovidone is in the range from about 1 : 1 to about 20: 1, preferably in the range from about 5 : 1 to about 15: 1.

11. The orodispersible tablet according to claim 1 , wherein the binder is selected from the group consisting of acacia, starch, tragacanth, methylcellulose, cellulose derivatives, gelatin, Polyethylene glycol, glucose, polyvinylpyrrolidone, starch paste, sodium alginate, sorbitol, povidone or any combinations thereof.

12. The orodispersible tablet according to claim 11, wherein the binder is povidone present in the range from about l%w/w to about 10%w/w, preferably in the range from about 2%w/w to about 8%w/w.

13. The orodispersible tablet according to claim 1, wherein the solubilizing agent is selected from the group consisting of egg yolk lecithin, gum arabic, hydrogenated castor oil, dipolyhydroxy stearate, hydrated silica, polysorbate, polyoxyl hydrogenated castor oil, sodium deoxycholate, hydroxypropyl methylcellulose, soya lecithin or any combinations thereof.

14. The orodispersible tablet according to claim 13, wherein the solubilizing agent is polysorbate present in the range from about 0.01%w/w to about 1 %w/w, preferably in the range from about 0.05%w/w to about 0.5%w/w.

15. The orodispersible tablet according to claim 1, wherein the lubricant is selected from the group consisting of boric acid, magnesium stearate, sodium stearyl fumarate, micronized polyoxy ethylene glycol, leucine, sodium benzoate, sodium acetate, sodium lauryl sulfate, stearic acid, sodium stearate, sodium oleate, calcium stearate, waxes or combinations thereof.

16. The orodispersible tablet according to claim 15, wherein the lubricant is magnesium stearate present in the range from about 0.1 %w/w to about 8%w/w, preferably in the range from about 0.5 %w/w to about 5 %w/w.

17. The orodispersible tablet according to claim 1, wherein the glidant is selected from the group consisting of ascorbyl palmitate, calcium palmitate, magnesium stearate, colloidal anhydrous silica, starch and talc or combinations thereof.

18. The orodispersible tablet according to claim 17, wherein the glidant is colloidal anhydrous silica present in the range from about 0.1 %w/w to about 8%w/w, preferably in the range from about 0.5%w/w to about 5%w/w.

19. The orodispersible tablet according to claim 1, wherein the sweetener is selected from the group consisting of cyclamate, acesulfame potassium, neo hesperidin dihydrochalcone, monoammonium glycyrrhizinate, saccharin sodium, sucralose, saccharin, aspartame or combinations thereof.

20. The orodispersible tablet according to claim 1, wherein the flavor is selected from the group consisting of peppermint flavor, cooling flavor, flavor oils and flavoring aromatic oil, peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil, thyme oil, oil of bitter almonds, vanilla, citrus oils, fruit essences or any combinations thereof.

21. The orodispersible tablet according to claim 1, further comprises sodium saccharin in the range from about 0.05%w/w to about 3.5%w/w, preferably in the range from about 0.1%w/w to about 1 %w/w and peppermint flavor is present in the range from about 0.05%w/w to about 3.5%w/w, preferably in the range from about 0.1%w/w to about 1 %w/w.

22. The orodispersible tablet according to claim 1, wherein the orodispersible tablet is manufactured by wet granulation method comprising steps of:

(a) Sieving spironolactone or pharmaceutically acceptable salts thereof, microcrystalline cellulose, maize starch, crospovidone, colloidal anhydrous silica, sodium saccharin, peppermint flavor through 40# sieve, and magnesium stearate was sieved through 60# sieve;

(b) Preparing binder solution by dissolving povidone in 50% of the total amount of purified water and polysorbate with continuous stirring until it becomes a clear viscous solution;

(c) Dry mixing of spironolactone, microcrystalline cellulose, maize starch, and Crospovidone in a rapid mixer granulator for 15 minutes;

(d) Adding the previously prepared binder solution to the above step (c) with continuous mixing at slow speed with intermittent addition of the remaining quantity of purified water;

(e) Drying the granules in a fluidized bed dryer with an inlet temperature of 50°C±5°C;

(f) Sieving the final granules through 24# sieve;

(g) Mixing of previously sifted Crospovidone, sodium saccharin, colloidal anhydrous silica, and peppermint flavor to the final blend of step (d) in blender;

(h) Blending of magnesium stearate in the blender with a pre-lubricated blend of step (e); (i) Compressing the final mixture into the tablet dosage form; and

(j) Packing of said tablets of spironolactone in PVC and PVDC blister pack and HDPE bottles with CR cap containing silica gel.

23. The orodispersible tablet according to claim 1, wherein 90% of spironolactone or pharmaceutically acceptable salts thereof is released within 60 minutes, preferably more than 90% is released within 45 minutes.

24. The orodispersible tablet according to claim 1, is used for the treatment of NYHA Class III-IV heart failure, edema associated with hepatic cirrhosis, edema associated with nephrotic syndrome, refractory edema associated with congestive cardiac failure, malignant ascites, hepatic cirrhosis with ascites, essential hypertension, primary hyperaldosteronism, aldosterone-producing adrenal adenomas and idiopathic hyperaldosteronism.

25. The orodispersible tablet according to claim 1, wherein:

(a) 10%w/w to about 30%w/w, preferably in the range from about 15%w/w to 25%w/w of spironolactone or pharmaceutically acceptable salts thereof;

(b) a combination of microcrystalline cellulose and maize starch present in the range from about 40%w/w to about 80%w/w, preferably in the range from about 55%w/w to about 75%w/w;

(c) 30%w/w to about 60%w/w, preferably in the range from about 40%w/w to about 50%w/w of microcrystalline cellulose;

(d) 10%w/w to about 40%w/w, preferably in the range from about 15%w/w to about 35%w/w of maize starch;

(e) 0.5 %w/w to about 15 %w/w, preferably in the range from about 1 %w/w to about 10 %w/w of crospovidone; (f) l%w/w to about 10%w/w, preferably in the range from about 2%w/w to about 8%w/w of povidone;

(g) 0.01 %w/w to about 1 %w/w, preferably in the range from about 0.05 %w/w to about 0.5 %w/w of polysorbate; (h) 0.1 %w/w to about 8%w/w, preferably in the range from about 0.5%w/w to about

5 %w/w of magnesium stearate;

(i) 0.1 %w/w to about 8%w/w, preferably in the range from about 0.5 %w/w to about 5 %w/w of colloidal anhydrous silica;

(j) 0.05 %w/w to about 3.5 %w/w, preferably in the range from about 0.1%w/w to about 1 %w/w of sodium saccharin; and

(k) 0.05 %w/w to about 3.5%w/w, preferably in the range from about 0.1 %w/w to about 1 %w/w of peppermint flavor.