A fast-disintegrating tablet of bisoprolol or pharmaceutically acceptable salts thereof and its process of preparation

Abstract

The present invention relates to a fast-disintegrating tablet manufactured by a direct compression method comprising bisoprolol or pharmaceutically acceptable salts thereof, at least one disintegrant, at least one diluent and one or more pharmaceutically acceptable excipients. The present invention is based on enhancing disintegration and dissolution, which is beneficial in the treatment and is very convenient for administration without the problem of swallowing and using water, thereby increasing patient compliance.

Description

[0001] A fast-disintegrating tablet of bisoprolol or pharmaceutically acceptable salts thereof and its process of preparation.

[0002] Field of the Invention

[0003] The present invention relates to a pharmaceutical composition of bisoprolol. The present invention relates to a fast-disintegrating tablet of bisoprolol or pharmaceutically acceptable salts thereof for oral administration. The present invention also relates to the process of the preparation of the same.

[0004] Background of the Invention

[0005] Bisoprolol was first disclosed in the U.S. Pat. No. 4,258,062. Bisoprolol is a selective beta-1 adrenergic receptor antagonist and is devoid of intrinsic sympathomimetic activity. When adrenergic neurotransmitters such as epinephrine activate 01 -receptors, both the blood pressure and heart rate increase, leading to greater cardiovascular work, and increasing the oxygen demand. By competitive inhibition of pl -adrenergic receptors, bisoprolol reduces cardiac workload by decreasing contractility and the need for oxygen. Bisoprolol also reduces the output of renin in the kidneys, which normally increases blood pressure. Bisoprolol's effects on the central nervous system may also include diminished sympathetic nervous system output from the brain, as well as decreased blood pressure and heart rate. Additionally, it inhibits beta2-adrenoceptors, which are primarily located in the bronchial and vascular musculature to retain selectivity. Bisoprolol is used in the management and treatment of hypertension and ischemic heart disease.

[0006] The IUPAC name of bisoprolol is l-(propan-2-ylamino)-3-[4-(2-propan-2- yloxyethoxymethyl) phenoxy] propan-2-ol. The marketed products of Bisoprolol in tablet form are available in four dosage strengths: 1.25mg, 2.5mg, 5 mg, and 10 mg for oral administration. Bisoprolol fumarate is a high permeability and high solubility drug which makes it belong to BCS class I in the Biopharmaceutical classification system. Bisoprolol has a long plasma half-life of 12 hours which make it a suitable candidate for designing fastdisintegrating tablet. The objective of the present invention is to prepare bisoprolol tablets having a faster disintegration time, and a faster dissolution rate, which is beneficial in the treatment and is very convenient for administration without the problem of swallowing and using water, thereby increasing patient compliance.

[0007] US 2004 / 0185099A1 discloses an oral multi-particulate bisoprolol formulation for once-daily oral administration. Each particle has a bisoprolol core encased in a polymeric coating. After coating, the multi-particulate is in the form of caplets, capsules, and particles for suspension prior to dosing, sachets, or tablets.

[0008] CZ20041178A3 discloses an oral tablet of bisoprolol. The process of this invention involves mixing bisoprolol fumarate with a fraction of a dry sprayed mixture of microcrystalline cellulose and lactose being added successively to the mixture being mixed, whereupon the obtained mixture can be further mixed with at least one pharmaceutically acceptable adjuvant and optionally with the last fraction of the dry sprayed mixture of microcrystalline cellulose and lactose and the obtained mixture is then molded to form a tablet. Hence, the obtained tablet can be optionally coated with a coating restricting or eliminating penetration of atmosphere components into the tablet.

[0009] The fast-disintegrating tablet of the present invention is a pharmaceutical formulation that rapidly disintegrates in the mouth. The fast-disintegrating tablet in the mouth allows for the administration of bisoprolol to a patient without having to simultaneously drink the liquid to ingest the formulation. For patients who have difficulty swallowing, such as the elderly, and patients with other conditions, taking bisoprolol in the form of a fast-disintegrating tablet may be easier. Summary of the Invention

[0010] In accordance with the present invention, the fast-disintegrating tablet for oral administration is prepared. The fast-disintegrating tablet comprises bisoprolol or pharmaceutically acceptable salts thereof, at least one disintegrant, at least one diluent, and one or more pharmaceutically acceptable excipients.

[0011] Another embodiment of the invention involves a process for preparing the fastdisintegrating tablet for oral administration. The fast-disintegrating tablet is manufactured by the direct compression method.

[0012] Another embodiment of the present invention can effectively treat hypertension and ischemic heart disease.

[0013] Objects of the Invention

[0014] The primary object of the present invention is to provide a fast-disintegrating tablet of bisoprolol or pharmaceutically acceptable salts thereof.

[0015] It is an object of the present invention to enhance the disintegration and dissolution of the drug for oral administration.

[0016] It is a further another object of the present invention is to provide a treatment that is effective and very convenient for administration without the need for water or swallowing difficulties, which will improve patient compliance.

[0017] It is a further another object of the present invention is to provide a stable fastdisintegrating tablet of bisoprolol or pharmaceutically acceptable salts thereof. Yet another object of the present invention is to provide fast disintegration of the dosage form on contact with saliva providing a good agreeable mouth feeling.

[0018] Detailed description of the Invention

[0019] The fast-disintegrating tablet of bisoprolol suitable for oral administration is the invention as further described herein. It also relates to its preparation method and the use of the fast-disintegrating tablet. The term “fast-disintegrating tablet” means a tablet that can disintegrate in the oral cavity in less than 3 minutes.

[0020] Furthermore, the term “fast-disintegrating tablet”, as used in the present invention, refers to the uncoated tablet that is intended to be placed in the mouth, with the help of saliva they disintegrate without the need for water. In conventional dosage form, there is a delay in disintegration and dissolution. But in the case of fast-disintegrating tablets, rapid disintegration in the oral cavity and dissolution is fast.

[0021] The term "about", as and when used in this specification, means ±10 % of the mentioned value.

[0022] According to one embodiment of the present invention is a fast-disintegrating tablet suitable for oral administration comprising bisoprolol, at least one disintegrant, and at least one diluent. In one embodiment, the bisoprolol is present in the range of about 0.25 %w / w to about 4 %w / w, preferably in the range of about 0.5 %w / w to about 2.5 %w / w.

[0023] As per one embodiment, a suitable diluent for the present invention is selected from the group consisting of dextrates, microcrystalline cellulose, dextrose, fructose, Sorbitol, pregelatinized starch, starch, xylitol, sucrose, maltodextrin, maltose, mannitol or combinations thereof. In the present invention, microcrystalline cellulose is preferred as a diluent in the range from about 20 %w / w to about 90 % w / w, preferably from about 35 %w / w to about 80% w / w, and mannitol is present in the range from about 10 %w / w to about 80 % w / w, preferably from about 15 %w / w to about 60% w / w. In the present invention, the combination of microcrystalline cellulose and mannitol is preferred as a diluent in the range of about 10 %w / w to about 98 %w / w, preferably in the range from about 15 %w / w to about 95 %w / w. In the development of tablets, the use of mannitol as a filler has increased due to its physicochemical properties, such as its nonhygroscopicity, chemical inertness, and advantageous tableting behavior, including compactability. Mannitol has a mild, sweet pleasant taste with a cooling effect in the mouth. Microcrystalline cellulose promotes the efficient dry blending of ingredients and provides excellent compression of tablets. Therefore, the combination of microcrystalline cellulose and mannitol is preferred as diluents in comparison with other diluents in the present invention.

[0024] As per one more embodiment, microcrystalline cellulose has a D 10 particle size distribution in the range of about 20 pm to about 60 pm, more preferably in the range of about 25 pm to 45 pm. The D 50 particle size distribution is in the range of about 60 pm to 160 pm, more preferably in the range of about 80 pm to 140 pm. The D 90 particle size distribution is in the range of about 150 pm to 300pm, more preferably in the range of about 180 pm to 280pm.

[0025] As per one another embodiment, a suitable disintegrant for the present invention is selected from a group consisting of methylcellulose, alginic acid, carboxymethylcellulose calcium, guar gum, carboxymethylcellulose Sodium, polacrilin potassium, croscarmellose sodium, poloxamer, sodium starch glycolate, and sodium alginate. Further, the disintegrant can be single or any combination thereof. Croscarmellose sodium is the preferred disintegrant for the present invention in the range from about 0.25 %w / w to about 6 %w / w, preferably in the range from about 0.5 %w / w to about 3 %w / w. In the present invention, the ratio of Croscarmellose sodium to a combination of microcrystalline cellulose and mannitol is in the range of 1 :80 to 1:98 and preferably it is in the range of 1:85 to 1:95. Croscarmellose sodium is internally cross-linked with sodium carboxymethylcellulose. Through the mechanisms of swelling, recovering elastic energy, and capillary action, croscarmellose sodium speeds up the wicking process. Further, it has the tendency to absorb water rapidly, so it swells significantly and results in rapid and uniform disintegration. Therefore, croscarmellose sodium is the disintegrant of choice for the fast-disintegrating tablet of bisoprolol fumarate.

[0026] As per one more embodiment of the present invention, a suitable lubricant is selected from the group consisting of boric acid, magnesium stearate, Sodium Stearyl fumarate, micronized poly oxy ethylene glycol, leucine, sodium benzoate, sodium acetate, sodium lauryl sulfate, stearic acid, sodium stearate, sodium oleate, calcium stearate, waxes or any combination thereof. Magnesium stearate is preferred as a lubricant for the present invention and is present in the range from about 0.25 %w / w to about 8 %w / w, preferably in the range from about 0.5 %w / w to about 4 %w / w, wherein the ratio of magnesium stearate to bisoprolol fumarate is 1 : 1 to 1 : 5 preferably in the range of about 1:2 to 1:4.

[0027] As per another embodiment of the present invention, at least one further pharmaceutically acceptable excipient is a sweetener selected from the group consisting of cyclamate, acesulfame potassium, neo hesperidin dihydrochalcone, monoammonium glycyrrhizinate, saccharin sodium, sucralose, saccharin, aspartame or any combination thereof. Acesulfame potassium is preferred as a sweetener for the present invention and is present in the range of about 0.5 %w / w to about 6 %w / w, preferably in the range of about 1 %w / w to about 4 %w / w. As per one another embodiment of the present invention, a flavoring agent is selected from a group consisting of menthol, floral fennel flavor, mint powder, vanillin, or orange flavor or combinations thereof. The orange flavor is preferred as a flavoring agent present in the range from about 0.25 %w / w to about 5 %w / w, preferably in the range from about 0.5 %w / w to about 3 %w / w.

[0028] As per preferred embodiment, the fast-disintegrating tablet of the present invention comprises bisoprolol or pharmaceutically acceptable salts thereof, at least one disintegrant and diluent. In addition, the fast-disintegrating tablet further comprises at least one pharmaceutically acceptable excipient selected from a sweetener, flavoring agent, and lubricant. The present invention has been made to solve the above- mentioned problems, and its object is to use bisoprolol or a pharmaceutically acceptable salt thereof as an active ingredient, which provides a faster disintegration time and faster dissolution rate. Bisoprolol is used for the treatment or prevention of hypertension and ischemic heart disease and is very convenient for administration without the problem of swallowing and using water thereby increasing patient compliance.

[0029] As per one preferred embodiment of the present invention comprising bisoprolol or pharmaceutically acceptable salts thereof, present in an amount from about 0.25 %w / w to about 4 %w / w, preferably in the range of about 0.5 %w / w to about 2.5 %w / w, the combination of microcrystalline cellulose and mannitol is preferred as a diluent in the range of about 10 %w / w to about 98 %w / w, preferably in the range from about 15 %w / w to about 95 %w / w, Croscarmellose sodium is the preferred disintegrant for the present invention in the range from about 0.25 %w / w to about 6 %w / w, preferably in the range from about 0.5 %w / w to about 3 %w / w, Magnesium stearate is preferred as a lubricant for the present invention and is present in the range from about 0.25 %w / w to about 8 %w / w, preferably in the range from about 0.5 %w / w to about 4 %w / w, acesulfame potassium is preferred as a sweetener for the present invention and is present in the range of about 0.5 %w / w to about 6 %w / w, preferably in the range of about 1 %w / w to about 4 %w / w and orange flavour is preferred as a flavouring agent for the present in the range from about 0.25 %w / w to about 5 %w / w, preferably in the range from about 0.5 %w / w to about 3 %w / w.

[0030] As per one more embodiment of the present invention, the ratio of a disintegrant to diluent is in the range of 1:80 to 1:98 and preferably it is in the range of 1:85 to 1:95. The ratio of Croscarmellose sodium to a combination of microcrystalline cellulose and mannitol is in the range of 1 :80 to 1 :98 and preferably it is in the range of 1 :85 to 1 :95. The ratio of lubricant to the drug is in the range of 1 : 1 to 1 : 5 preferably it is in the range of about 1:2 to 1:4. The ratio of magnesium stearate to bisoprolol fumarate is in the range of 1 : 1 to 1 :5 preferably it is in the range of about 1 :2 to 1:4.

[0031] Another embodiment of the present invention is to manufacture fast-disintegrating tablets containing bisoprolol by direct compression method, which is one of the most economical methods.

[0032] As per one another embodiment, the disintegrating time of the bisoprolol fastdisintegrating tablet is less than 3 minutes, preferably less than 2 minutes.

[0033] As per another embodiment, 85 % of the bisoprolol is released in 30 minutes, preferably more than 90 % is released within 20 minutes.

[0034] As per one embodiment of the present invention, packaging material for a fastdisintegrating tablet of bisoprolol is selected from the Polypropylene Bottle with Silica canister, PP Bottle with an Oxygen scavenger, HDPE Bottle, HDPE Bottle with Silica canister, HDPE Bottle with an Oxygen scavenger, and Alu-Alu Blister. In the present invention, the Alu-Alu Blister or HDPE Bottle with a Silica canister is preferred as packaging material to deliver the desired physicochemical parameters.

[0035] As per one more embodiment, the direct compression method is used to manufacture the fast-disintegrating tablet. Bisoprolol fumarate, Mannitol, Microcrystalline cellulose, and Croscarmellose Sodium are sieved separately through a 40# sieve. Acesulfame potassium, orange flavor, and magnesium stearate are Sieved separately through a 60# sieve. In a blender, mannitol, microcrystalline cellulose, and bisoprolol fumarate are blended and mixed. Previously sifted croscarmellose sodium. Acesulfame potassium, and the orange fla vor are added to the above blend and mixed. At last, the previously sifted magnesium stearate is added to the above mixture and blended in a blender. Finally, the lubricated mixture is compressed to form tablets. The prepared tablets were packed in Alu-Alu Blister or HDPE Bottle with a Silica canister preferred as packaging materials to deliver the desired physicochemical parameters.

[0036] 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.

[0037] Example 1:

[0038] The fast-disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in table I for different dose strengths are 1.25 mg, 2.5 mg, 5 mg, and 10 mg of bisoprolol:

[0039] TABLE-I

[0040] Manufacturing process:

[0041] Bisoprolol fumarate, Mannitol, Microcrystalline cellulose, and Croscarmellose Sodium are sieved separately through a 40# sieve. Acesulfame potassium, orange flavor, and magnesium stearate are Sieved separately through a 60# sieve. In a blender, mannitol, microcrystalline cellulose, and bisoprolol fumarate are blended and mixed. Previously sifted croscarmellose sodium. Acesulfame potassium, and the orange flavor are added to the above blend and mixed. At last, the previously sifted magnesium stearate is added to the above mixture and blended in a blender.

[0042] The blend flow was not good so, further compression activity was not performed. To optimize blend flow, it was necessary to decrease the concentration of Microcrystalline cellulose.

[0043] Example 2:

[0044] The fast-disintegrating tablet was prepared according to the procedure described below using the formulation having the ingredients shown in table II for different dose strengths are 1.25 mg, 2.5 mg, 5 mg, and 10 mg of bisoprolol: TABLE- II

[0045] Manufacturing process:

[0046] Bisoprolol fumarate, Mannitol, Microcrystalline cellulose, and Croscarmellose Sodium are sieved separately through a 40# sieve. Acesulfame potassium, orange flavor, and magnesium stearate are Sieved separately through a 60# sieve. In a blender, mannitol, microcrystalline cellulose, and bisoprolol fumarate are blended and mixed. Previously sifted croscarmellose sodium, Acesulfame potassium, and the orange flavor are added to the above blend and mixed. At last, the previously sifted magnesium stearate is added to the above mixture and blended in a blender.

[0047] Still, the blending flow was not good so, further compression activity was not performed. To optimize blend flow, it was necessary to change the grade of microcrystalline cellulose.

[0048] Example 3:

[0049] The fast-disintegrating tablet was prepared according to the procedure described below using the formulation having the ingredients shown in table III for different dose strengths are 1.25 mg, 2.5 mg, 5 mg, and 10 mg of bisoprolol:

[0050] TABLE-III

[0051] Manufacturing process:

[0052] Bisoprolol fumarate, Mannitol, Microcrystalline cellulose, and Croscarmellose Sodium are sieved separately through a 40# sieve. Acesulfame potassium, orange flavor, and magnesium stearate are Sieved separately through a 60# sieve. In a blender, mannitol, microcrystalline cellulose, and bisoprolol fumarate are blended and mixed. Previously sifted croscarmellose sodium, Acesulfame potassium, and the orange flavor are added to the above blend and mixed. At last, the previously sifted magnesium stearate is added to the above mixture and blended in a blender. Finally, the lubricated mixture is compressed to form tablets. Weight variation was observed during compression due to blend flow issues. To optimize blend flow, it was necessary to increase the concentration of mannitol.

[0053] The tablets present the characteristics mentioned in the table below:

[0054] Example 4:

[0055] The fast-disintegrating tablet was prepared according to the procedure described below using the formulation having the ingredients shown in table IV for different dose strengths are 1.25 mg, 2.5 mg, 5 mg, and 10 mg of bisoprolol:

[0056] TABLE-IV

[0057] Manufacturing process:

[0058] Bisoprolol fumarate, Mannitol, Microcrystalline cellulose, and Croscarmellose Sodium are sieved separately through a 40# sieve. Acesulfame potassium, orange flavor, and magnesium stearate are Sieved separately through a 60# sieve. In a blender, mannitol, microcrystalline cellulose, and bisoprolol fumarate are blended and mixed. Previously sifted croscarmellose sodium, Acesulfame potassium, and the orange flavor are added to the above blend and mixed. At last, the previously sifted magnesium stearate is added to the above mixture and blended in a blender. Finally, the lubricated mixture is compressed to form tablets.

[0059] The blend flow was proper but a Capping problem was observed during compression. To minimize the Capping problem, it was necessary to decrease the concentration of Lubricant.

[0060] The tablets present the characteristics mentioned in the table below:

[0061] Example 5:

[0062] The fast-disintegrating tablet was prepared according to the procedure described below using the formulation having the ingredients shown in table V for different dose strengths are 1.25 mg, 2.5 mg, 5 mg, and 10 mg of bisoprolol:

[0063] TABLE-V

[0064] Manufacturing process:

[0065] Bisoprolol fumarate, Mannitol, Microcrystalline cellulose, and Croscarmellose Sodium are sieved separately through a 40# sieve. Acesulfame potassium, orange flavor, and magnesium stearate are Sieved separately through a 60# sieve. In a blender, mannitol, microcrystalline cellulose, and bisoprolol fumarate are blended and mixed. Previously sifted croscarmellose sodium, Acesulfame potassium, and the orange flavor are added to the above blend and mixed. At last, the previously sifted magnesium stearate is added to the above mixture and blended in a blender. Finally, the lubricated mixture is compressed to form tablets. The prepared tablets were packed in Alu-Alu Blister or HDPE Bottle with a Silica canister preferred as a packaging material to deliver the desired physicochemical parameters.

[0066] All the physical and chemical parameters of the tablets were found satisfactory.

[0067] Example 6: The Dissolution profile of the tablet prepared according to example 5

[0068] The conditions of dissolution are the following:

[0069] Apparatus: USP type II (paddle)

[0070] Rate of rotation: 50

[0071] Volume: 500ml

[0072] Temperature: 37°C ± 0.5°C

[0073] Detection: 225nm

[0074] Dissolution medium: Water

[0075] Result: The fast-disintegrating tablet of bisoprolol was tested for its dissolution profile measured in 500mL of Water at 50 RPM in USP II (Paddle) apparatus and the active ingredient of the tablet is released in more than 95% in 15 minutes. Example 7: The tablet prepared according to example 5 were subjected to a stability study of 25°C / 60% RH and 40°C / 75% RH for 3 and 6 months. Results are tabulated below.

[0076] Bisoprolol 1.25mg fast-disintegrating tablets

[0077]

[0078] Bisoprolol 2.5mg fast-disintegrating tablets

[0079]

[0080] Bisoprolol 5mg fast-disintegrating tablets

Claims

Claims:

1. A fast-disintegrating tablet of bisoprolol for oral administration comprising: a) bisoprolol or pharmaceutically acceptable salts thereof, is present in an amount ranging from about 0.25 %w / w to about 4 %w / w, preferably in the range from about 0.5 %w / w to about 2.5 %w / w; b) at least one diluent; c) at least one disintegrant is present in the range of about 0.25 %w / w to about 6 %w / w, preferably in the range of about 0.5 %w / w to about 3 %w / w; d) at least one lubricant is present in the range from about 0.25 %w / w to about 8 %w / w, preferably in the range from about 0.5 %w / w to about 4%w / w; and e) at least one or more pharmaceutically acceptable excipients.

2. The fast-disintegrating tablet according to claim 1, wherein the diluent is selected from the group consisting of dextrates, microcrystalline cellulose, dextrose, fructose, Sorbitol, pregelatinized starch, starch, xylitol, sucrose, maltodextrin, maltose, mannitol or combinations thereof.

3. The fast-disintegrating tablet according to claim 2, wherein the diluent is mannitol present in the range from about 10 %w / w to about 80 % w / w, preferably from about 15 %w / w to about 60 % w / w.

4. The fast-disintegrating tablet according to claim 2, wherein the diluent is microcrystalline cellulose present in the range from about 20 %w / w to about 90 % w / w, preferably from about 35 %w / w to about 80 % w / w.

5. The fast-disintegrating tablet according to claim 4, wherein the D 90 particle size of microcrystalline cellulose, is in the range of about 150 pm to 300 pm, more preferably in the range of about 180 pm to 280 pm.

6. The fast-disintegrating tablet according to claim 4, wherein the D 50 particle size of microcrystalline cellulose, is in the range of about 60 pm to 160 pm, more preferably in the range of about 80 pm to 140 pm.

7. The fast-disintegrating tablet according to claim 4, wherein the D 10 particle size of microcrystalline cellulose, is in the range of about 20 pm to 60 pm, more preferably in the range of about 25 pm to 45 pm.

8. The fast-disintegrating tablet according to claim 2, wherein the diluent is a combination of microcrystalline cellulose and mannitol present in the range of about 10 %w / w to about 98 %w / w, preferably in the range of about 15 %w / w to about 95 %w / w.

9. The fast-disintegrating tablet according to claim 1, wherein the disintegrant is selected from the group consisting of methylcellulose, alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, polacrilin potassium, croscarmellose sodium, guar gum, poloxamer, sodium starch glycolate, and sodium alginate or any combination thereof.

10. The fast-disintegrating tablet according to claim 9, wherein the disintegrant is Croscarmellose sodium.

11. The fast-disintegrating tablet according to claim 1, wherein the ratio of a disintegrant to diluent is in the range of 1 : 80 to 1 :98 and preferably it is in the range of 1:85 to 1:95.

12. The fast-disintegrating tablet according to claim 11, wherein the ratio of Croscarmellose sodium to a combination of microcrystalline cellulose and mannitol is in the range of 1 : 80 to 1 :98 and preferably in the range of 1 : 85 to 1 :95.

13. The fast-disintegrating tablet according to claim 1, wherein the lubricant is selected from the group consisting of boric acid, magnesium stearate, sodium Stearyl fumarate, micronized polyoxyethylene glycol, leucine, sodium benzoate, sodium acetate, sodiumlauryl sulfate, stearic acid, sodium stearate, sodium oleate, calcium stearate or combinations thereof.

14. The fast-disintegrating tablet according to claim 13, wherein the lubricant is magnesium stearate.

15. The fast-disintegrating tablet according to claim 1, wherein the ratio of a lubricant to the drug is in the range of 1 : 1 to 1 :5 preferably it is in the range of about 1 :2 to 1 :4.

16. The fast-disintegrating tablet according to claim 15, wherein the ratio of magnesium stearate to bisoprolol fumarate is in the range of 1 : 1 to 1:5 and preferably in the range of 1:2 to 1:4.

17. The fast-disintegrating tablet according to claim 1, wherein one or more pharmaceutically acceptable excipients, are selected from the sweeteners or flavoring agents.

18. The fast-disintegrating tablet according to claim 17, 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 is present in the range of about 0.5 % w / w to about 6 % w / w, preferably in the range of about 1 % w / w to about 4 % w / w.

19. The fast-disintegrating tablet according to claim 17, wherein the flavoring agent is selected from the group consisting of menthol, floral fennel flavor, mint powder, vanillin, or orange flavor or combinations thereof is present in the range from about 0.25 %w / w to about 5 %w / w, preferably in the range from about 0.5 %w / w to about 3 %w / w.

20. The fast-disintegrating tablet according to claim 17, further comprises acesulfame potassium and orange flavor.

21. The fast-disintegrating tablet according to claim 1, wherein the fast-disintegrating tablet is manufactured by the direct compression method comprising the steps:(a) Sieving bisoprolol fumarate or pharmaceutically acceptable salts thereof, Mannitol, Microcrystalline cellulose, and Croscarmellose Sodium separately through a 40# sieve and Acesulfame potassium, orange flavor, and magnesium stearate separately through a 60# sieve;(b) Blending mannitol, microcrystalline cellulose, and bisoprolol fumarate in a blender;(c) Mixing of Previously sifted croscarmellose sodium, acesulfame potassium, and orange flavor to the above blend;(d) Adding previously sifted magnesium stearate to the above mixture of step (c) and blend in a blender;(e) Compressing the lubricated mixture into the tablet dosage form; and(f) Packing of the tablet into an Alu-Alu Blister or HDPE Bottle with a Silica canister.

22. The fast-disintegrating tablet according to claim 1, wherein the fast-disintegrating tablet is disintegrated upon contact with saliva in less than 3 minutes, preferably less than 2 minutes.

23. The fast-disintegrating tablet according to claim 1, wherein 85 % of the bisoprolol or pharmaceutically acceptable salts thereof, is released within 30 minutes, preferably more than 90 % is released within 20 minutes.

24. The fast-disintegrating tablet according to claim 1, for use in the treatment of hypertension and ischemic heart disease.

25. The fast-disintegrating tablet for oral administration comprising: a) 0.25 %w / w to about 4 %w / w, preferably in the range of about 0.5 %w / w to about 2.5 %w / w of bisoprolol or pharmaceutically acceptable salts thereof;b) 20 %w / w to about 90 % w / w, preferably from about 35 %w / w to about 80% w / w of microcrystalline cellulose; c) 10 %w / wto about 80 % w / w, preferably from about 15 %w / wto about 60% w / w of mannitol; d) a combination of microcrystalline cellulose and mannitol present in the range of about 10 %w / w to about 98 %w / w, preferably in the range of about 15 %w / w to about 95 %w / w; e) 0.25 %w / w to about 6 %w / w, preferably in the range of about 0.5%w / w to about 3 %w / w of croscarmellose sodium; f) 0.25 %w / w to about 8 %w / w, preferably in the range from about 0.5 %w / w to about 4% w / w of magnesium stearate; g) 0.5 %w / w to about 6 %w / w, preferably in the range of about 1 %w / w to about 4 % w / w of acesulfame potassium; and h) 0.25 %w / w to about 5 %w / w, preferably in the range from about 0.5 % w / w to about 3 % w / w of orange flavor.

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