DESC:FIELD OF THE INVENTION

The present invention relates to dispersible tablet composition of dolutegravir or its salts and one or more pharmaceutically acceptable excipients and process for preparation of such compositions.

BACKGROUND OF THE INVENTION

Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle.
Dolutegravir sodium, is described chemically as Sodium (4R,12aS)-9-{[(2,4-difluoro phenyl)methyl]carbamoyl}-4-methyl6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5] pyrazino[2,1-b] [1,3]oxazin-7-olate and has the following structural formula,

In the United States, ViiV Healthcare is marketing dolutegravir as 10mg, 25mg, 50mg immediate release oral tablets under the trade name Tivicay®. Dolutegravir is also available in combination with other drugs such as abacavir and lamivudine and rilpivirine.
Dolutegravir and its combinations have been approved for the treatment of HIV infections.
Dolutegravir is slightly soluble in water at pH 5.0 and 6.5. It is practically insoluble at pH 1.2 in aqueous media. Dolutegravir is classified as BCS Class II drug i.e., low soluble and high permeable. The oral bioavailability of this class of drugs is generally limited during dissolution phenomenon when administered in final dosage form.
US Patent No. 8,129,385 disclose dolutegravir, its sodium salt and its use in the treatment of HIV infections.
WO2011094150 disclose combination of dolutegravir with other therapeutic agents such as abacavir, efavirenz, and lopinavir.
WO2015140569 disclose nanoparticulate formulation of dolutegravir.
Prior art disclose the use of dolutegravir in combination with other antiretroviral drugs for the treatment of HIV. However, problems that are associated with the solubility and bioavailability of dolutegravir and patient compliance especially for pediatric and geriatric patients are yet to be addressed to yield the better bioavailability and better ADME profile.
Therapeutically active compounds or drugs are frequently administered to patients in tablet form where the drug is intended for oral administration since tablets are an especially convenient pharmaceutical form for manufacture, storage and general usage. However, problems may arise with the administration of such tablets to patients who have difficulty in swallowing the tablets (for example older patients, children or more seriously ill patients).
Thus there is a need for development of pharmaceutical compositions of dolutegravir with improved solubility, bioavailability and patient compliance.
A solution to such problems is to formulate the tablets in a form whereby they can be dispersed in water to form a dispersion containing the drug which can then be consumed by the patient.
SUMMARY OF THE INVENTION

One general aspect of the present invention provides dispersible tablet composition comprising dolutegravir or its salts and at least one pharmaceutically acceptable excipient.
Another aspect of the present invention provides dispersible tablet composition to form dispersion in water, which can then be consumed by the patient comprising dolutegravir sodium and at least one pharmaceutically acceptable excipient.
Another aspect of the present invention provides dispersible tablet composition comprising 5 mg to 10 mg of dolutegravir or its salts and at least one pharmaceutically acceptable excipient.
Another aspect of the present invention provides dispersible tablet composition comprising 5 mg to 10 mg of dolutegravir sodium having d90 particle size less than 50µm.
Another aspect of the present invention provides dispersible tablet composition comprising dolutegravir sodium having d90 particle size less than 50µm and at least one pharmaceutically acceptable excipient for use in combination with one or more other antiretroviral agents for the treatment of HIV infection.
Another aspect of the present invention provides dispersible tablet composition comprising dolutegravir or its salts and at least one pharmaceutically acceptable excipient, wherein the composition disintegrates in water within 3 minutes and shows dissolution of more than 60% within 30 minutes.
Another general aspect of the present invention provides dispersible tablet composition comprising 5 mg or 10 mg of dolutegravir or its salts and at least one pharmaceutically acceptable excipient, wherein the composition exhibits dissolution of more than 60% within 30 minutes.
The details of one or more embodiments of the present invention are set forth in the description below. Other features, objects and advantages of the invention will be apparent from the description.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides dispersible tablet composition to form dispersion in water, which can then be consumed by the patient comprising dolutegravir or its salts and at least one pharmaceutically acceptable excipient.
The term "Dolutegravir" is used in broad sense to include not only "Dolutegravir" per se but also its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable anhydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable esters, pharmaceutically acceptable isomers, pharmaceutically acceptable polymorphs, pharmaceutically acceptable prodrugs, pharmaceutically acceptable tautomers, pharmaceutically acceptable complexes etc. Preferably, Dolutegravir sodium.
The term “pharmaceutically acceptable” as used herein means that which is useful in preparing a pharmaceutical composition that is generally safe and non-toxic.
The term “excipients” as used herein means a component of a pharmaceutical product that is not an active ingredient. The excipients that are useful in preparing a pharmaceutical composition are generally safe and non-toxic.
As used in the specification and the appended claims, the singular forms “a”, “an”, and “the” include plural references unless the context clearly dictates otherwise. Thus for example, reference to “a method” includes one or more methods, and/or steps of the type described herein and/or which will become apparent to those persons skilled in the art upon reading this disclosure so forth.
"Dispersible tablet" means a tablet to be used for producing an aqueous suspension for swallowing.
One aspect of the present invention provides dispersible tablet composition to form dispersion in water, which can then be consumed by the patient comprising dolutegravir or its salts and at least one pharmaceutically acceptable excipient.
Another aspect of the present invention provides dispersible tablet composition to form dispersion in water, which can then be consumed by the patient comprising dolutegravir sodium and at least one pharmaceutically acceptable excipient.
Another aspect of the present invention provides dispersible tablet composition comprising 5 mg to 10 mg of dolutegravir or its salts and at least one pharmaceutically acceptable excipient.
Another aspect of the present invention provides dispersible tablet composition comprising 5 mg to 10 mg of dolutegravir sodium having d90 particle size less than 50µm and at least one pharmaceutically acceptable excipient.
Preferably, the d90 particle size of dolutegravir sodium is less than 40µm, more preferably less than 25µm, most preferably less than 15µm.
Particle size is determined by means of laser diffractometry.
The present invention provides dispersible tablet composition of dolutegravir or its salts to form dispersion for use in pediatric and/or geriatric population.
Another aspect of the present invention provides dispersible tablet composition of dolutegravir or its salts with a disintegration time of less than 3 minutes, preferably less than 90 seconds.
Another aspect of the present invention provides dispersible tablet composition of dolutegravir or its salts exhibits dissolution of at least 60% at about 30 minutes at a temperature of 37±0.5°C in 900 ml of 0.01M pH 6.8 phosphate buffer containing 0.50% w/v sodium dodecyl sulfate using USP II paddle apparatus at a speed of about 50 rpm.
The dispersible tablet composition comprising dolutegravir or its salts in an amount of 0.1 to 30% by total weight of the composition, preferably, from 1% to 10%, more preferably, from about 2% to about 7%.
Pharmaceutically acceptable excipients for use in the dispersible tablet composition of dolutegravir sodium include, but are not limited to diluents, fillers/bulking agents, binders, disintegrants, surfactants, lubricants, glidants and taste masking agents such as sweeteners.
Suitable diluents/fillers or bulking agents include, but are not limited to mannitol, xylitol, microcrystalline cellulose, lactose, calcium carbonate, dibasic calcium phosphate, sucrose, tribasic calcium phosphate, calcium sulfate, compressible sugars, confectioner's sugar, dextrates, dextrin, dextrose, magnesium carbonate, magnesium oxide, maltodextrin, polymethacrylates, powdered cellulose, powdered sugar, pregelatinized starch, sodium chloride, sorbitol, starch and combinations thereof. The diluent/filler may be present in an amount from about 10% w/w to about 80% w/w of the total weight of the composition.
Suitable binders include, but are not limited to one or more of polyvinyl pyrrolidone, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carbomers, dextrin, ethyl cellulose, methylcellulose, shellac, zein, gelatin, gum arabic, polymethacrylates, polyvinyl alcohol, polyethylene glycol, carrageenan, polyethylene oxide, waxes, pullulan, agar, tragacanth, veegum, pregelatinized starch, sodium alginate, gums, sugars such as sucrose, maltose, dextrose, lactose, amylase, synthetic resins and combinations thereof. The amount of binder may be present in an amount from about 0.5% to about 10% by total weight of the composition.
Suitable disintegrants include, but are not limited to agar, alginic acid, bentonite, carboxymethylcellulose calcium, carboxymethylcellulose sodium, carboxymethylcellulose, cellulose, a cation exchange resin, cellulose, gums, citrus pulp, colloidal silicon dioxide, corn starch, croscarmellose sodium, crospovidone, guar gum, hydrous aluminum silicate, magnesium aluminum silicate, methyl cellulose, microcrystalline cellulose, modified cellulose gum, modified corn starch, powdered cellulose, povidone, pregelatinized starch, sodium alginate, sodium starch glycolate, starch, silicates and combinations thereof. The amount of disintegrant may be present in an amount from about 5.0% to about 40% by total weight of the composition.
Suitable lubricants, but are not limited to magnesium stearate, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, light mineral oil, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc, zinc stearate, and combinations thereof. The lubricant may be present in a concentration of about 0.1% w/w to about 4.0% w/w of the composition.
Suitable surfactants include, but are not limited to, polyoxyethylene castor oil derivates, e.g. polyoxyethyleneglycerol triricinoleate or polyoxyl 35 castor oil (Cremophor EL; BASF Corp.) or polyoxyethyleneglycerol oxystearate such as polyethylenglycol 40 hydrogenated castor oil (Cremophor RH 40, also known as polyoxyl 40 hydrogenated castor oil or macrogolglycerol hydroxystearate) or polyethylenglycol 60 hydrogenated castor oil (Cremophor RH 60); or a mono fatty acid ester of polyoxyethylene sorbitan, such as a mono fatty acid ester of polyoxyethylene (20) sorbitan, e.g. polyoxyethylene (20) sorbitan monooleate (Tween 80), polyoxyethylene (20) sorbitan monostearate (Tween 60), polyoxyethylene (20) sorbitan monopalmitate (Tween 40), or polyoxyethylene (20) sorbitan monolaurate (Tween 20). Other non-limiting examples of suitable surfactants include polyoxyethylene alkyl ethers, e.g. polyoxyethylene (3) lauryl ether, polyoxyethylene (5) cetyl ether, polyoxyethylene (2) stearyl ether, polyoxyethylene (5) stearyl ether; polyoxyethylene alkylaryl ethers, e.g. polyoxyethylene (2) nonylphenyl ether, polyoxyethylene (3) nonylphenyl ether, polyoxyethylene (4) nonylphenyl ether, polyoxyethylene (3) octylphenyl ether; polyethylene glycol fatty acid esters, e.g. PEG-200 monolaurate, PEG-200 dilaurate, PEG-300 dilaurate, PEG-400 dilaurate, PEG-300 distearate, PEG-300 dioleate; alkylene glycol fatty acid mono esters, e.g. propylene glycol monolaurate (lauroglycol, such as lauroglycol FCC); sucrose fatty acid esters, e.g. sucrose monostearate, sucrose distearate, sucrose monolaurate, sucrose dilaurate; sorbitan fatty acid mono esters such as sorbitan mono laurate (Span 20), sorbitan monooleate, sorbitan monopalnitate (Span 40), or sorbitan stearate; D-alpha-tocopheryl polyethylene glycol 1000 succinate; or a combination or mixture thereof. Other suitable surfactants include, but are not limited to, block copolymers of ethylene oxide and propylene oxide, also known as polyoxyethylene polyoxypropylene block copolymers or polyoxyethylene polypropyleneglycol, such as Poloxamer 124, Poloxamer 188, Poloxamer 237, Poloxamer 388, or Poloxamer 407 (BASF Wyandotte Corp.), preferably, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, Gelucire 44/14, Gelucire 50/13, D-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), propylene glycol laurate, sodium lauryl sulfate, and sorbitan monolaurate. The surfactant may be present in a concentration of up to 10% w/w of the composition.
Suitable taste masking agents include, but are not limited to, one or more of polymers, and sweeteners. The taste masking agents may be present in a concentration of about 0.1% to about 10% w/w of the composition.
Examples of polymers include but not limited to cellulose acetate, polyacrylates, cellulose derivatives such as hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxylethyl cellulose; and the like, preferably, polyacrylates (commercially available as Eudragit NE, NM, RL and RS grades), most preferably, Eudragit NM 30D, NE 30D and NE 40D).
Examples of sweeteners include but not limited to one or more of aspartame, saccharin, sucralose, glycyrrhizin; and the like.
Examples of flavors include but not limited to cinnamon, wintergreen, eucalyptus, spearmint, peppermint, menthol, anise as well as fruit flavors such as apple, pear, peach, vanilla, strawberry, cherry, apricot, orange, watermelon, banana and the like; bean-derived flavors, such as coffee, cocoa and the like or mixtures thereof.
Another aspect of the present invention provides dispersible tablet composition of dolutegravir or its salts comprises commercially available combination of excipients. For example “F-Melt Type C” containing D-Mannitol, xylitol, anhydrous dibasic calcium phosphate, crospovidone, microcrystalline cellulose.
Another aspect of the present invention provides dispersible tablet composition of dolutegravir comprising:
i. 2.0% to 7.0 % of Dolutegravir sodium,
ii. 10% to 80% of diluent/filler,
iii. 0.5% to 10% of binder,
iv. 5% to 40% of disintegrant,
v. 0.1% to 10.0% of sweetner,
vi. 0.1% to 4.0% of lubricant.
Another aspect of the present invention provides dispersible tablet composition of dolutegravir comprising:
i. 2.0% to 7.0 % of Dolutegravir sodium,
ii. 10% to 80% of Microcrystalline cellulose,
iii. 2.0% to 15% of Mannitol,
iv. 0.1% to 5% of sodium starch glycolate,
v. 0.5% to 5% of povidone,
vi. 0.1 to 6.0% of Ethyl Acrylate and Methyl Methacrylate Copolymer,
vii. 2.0% to 25% of crospovidone,
viii. 20% to 80% of F-melt Type C,
ix. 0.1% to 2.0% of aspartame, and
x. 0.1% to 2% Magnesium stearate.

Dispersible tablet composition of the present invention are prepared by direct compression, dry granulation or wet granulation. Preferably, by wet granulation.
Suitable solvents that may be used in granulation include, but are not limited to water, methanol, ethanol, isopropyl alcohol, acetone, methylene chloride, dichloromethane, dimethyl sulfoxide and the like and mixtures thereof.
The present invention provides dispersible tablet composition of dolutegravir soidum for use in combination with one or more other antiretroviral agents for the treatment of HIV infection.

EXAMPLES
The invention is further illustrated by the following examples which are provided to be exemplary of the invention and do not limit the scope of the invention. While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

Example 1:

S.No Ingredients Mg/ Tab
Intra-Granular
1 Dolutegravir sodium# 5.260
2 Microcrystalline cellulose 6.000
3 Mannitol USP 14.540
4 Sodium starch glycolate 1.500
5 Polyvinyl pyrrolidone 1.500
6 Eudragit NM 30D 3.000
Extra-Granular
7 F-Melt Type C* 83.200
8 Crospovidone 30.000
9 Sodium starch glycolate 3.000
10 Aspartame 0.750
11 Magnesium Stearate 1.250
Total weight of tablet 150.00
*contains D-Mannitol, xylitol, anhydrous dibasic calcium phosphate, crospovidone, microcrystalline cellulose.
# 5.260mg of Dolutegravir sodium is equivalent to 5.000 mg of dolutegravir.

Manufacturing process:
Intra-granular:
1. Microcrystalline cellulose, Mannitol, Sodium starch glycolate and Polyvinyl pyrrolidone sifted separately through mesh #30.

2. Dolutegravir sodium was co-sifted with above material through mesh #20.

3. The above material is loaded into rapid mixer granulator and dry mixed for 15 minutes.

4. Eudragit NM30D was added to above step over a short period and wet mass was kneaded.

5. The wet mass was dried by maintaining inlet temperature at 60°C±5°C (55 – 65°C) and with suitable fluidization upto get loss on drying in the range of 2.5%±0.5%.

6. The dried granules sifted through mesh #30 and retentions were milled using multi mill.

Extra granular:

7. F-melt type C, Sodium starch glycolate, Crospovidone and Aspartame were sifted separately through mesh #30. Magnesium stearate sifted through mesh #40.

8. Milled granules of Dolutegravir intra-granular part and materials of step 8 were added except magnesium stearate to a suitable blender and blended.

9. Magnesium stearate was added to above step and lubricated.

Compression:

10. The lubricated blend is compressed into tablets using suitable tooling.

Example 2:

S.No Ingredients Mg/ Tab
Intra-Granular
1 Dolutegravir sodium# 10.520
2 Microcrystalline cellulose 4.080
3 Mannitol USP 10.000
4 Hydroxypropylmethyl cellulose 9.000
5 Eudragit NM 30D 3.000
Extra-Granular
6 F-Melt Type C 18.200
7 Crospovidone 14.00
8 Sodium starch glycolate 6.00
9 Fumed silica 0.800
10 Vanilla Flavor 0.400
11 Magnesium Stearate 1.000
Total weight of tablet 77.000
# 5.260mg of Dolutegravir sodium is equivalent to 5.000 mg of dolutegravir.

Manufacturing process: Same as Example 1.

Examples 3 and 4:

S. No Ingredients mg/Tab
Ex-3 Ex-4
Intra-Granular
1 Dolutegravir sodium# 10.520 10.520
2 Microcrystalline cellulose
12.000 12.000
3 Mannitol USP 29.080 29.080
4 Sodium starch glycolate 3.000 3.000
5 Polyvinyl pyrrolidone 3.000 3.000
6 Eudragit NM 30D 4.500 6.000
Extra-Granular
7 F-Melt Type C 18.700 166.400
8 Crospovidone 14.000 60.000
9 Sodium starch glycolate 6.000 6.000
10 Fumed silica 0.800 -
11 Aspartame - 1.500
12 Vanilla flavor 0.400 -
13 Magnesium Stearate 1.000 2.500
Total weight of tablet 103.000 300.00
# 5.260mg of Dolutegravir sodium is equivalent to 5.000 mg of dolutegravir.

Manufacturing process: Same as Example 1

Dissolution Data:
Dissolution test was performed for tablets prepared as per the above examples using USP apparatus II, 50 rpm, in 900 ml of 0.01M pH 6.8 phosphate buffer containing 0.25% w/v sodium dodecyl sulfate (SDS).
Time in Minutes % Drug release
Ex-1 Ex-2 Ex-3 Ex-4
5 50 48 60 40
10 61 57 71 54
15 67 62 76 62
20 71 66 79 67
30 74 70 80 73
45 78 74 84 78

In all the examples, dispersible tablets of Dolutegravir sodium composition exhibits dissolution more than 60% in 30 minutes.

Examples 5 and 6:

S. No Ingredients mg/Tab % w/w
Ex-5 Ex-6
Intra-Granular
1. Dolutegravir Sodium# 10.520 5.260 3.51
2. Microcrystalline Cellulose 12.000 6.000 4
3. Mannitol USP 29.080 14.540 9.69
4. Sodium Starch Glycolate 3.000 1.500 1
5. Povidone 3.000 1.500 1
6. Eudragit NM 30D 5.400 2.700 5.4
7. Purified Water 8.670 4.330 0
Extra Granular
8. F-Melt Type C 80.000 40.000 26.67
9. Microcrystalline Cellulose 85.750 42.880 28.59
10. Crospovidone 60.000 30.000 20
11. Sodium Starch Glycolate 6.000 3.000 2
12. Aspartame 1.500 0.750 0.5
13. Magnesium Stearate 3.750 1.880 1.25
Weight of core tablet (mg) 300.000 150.000 100
# 5.260mg of Dolutegravir sodium is equivalent to 5.000 mg of dolutegravir.

Manufacturing process:

Intra-granular:

1. Dolutegravir sodium was co-sifted along with Microcrystalline Cellulose, Povidone and Sodium starch glycolate through mesh #30.

2. Mannitol was co-sifted along with above material through mesh #30.

3. The above material is loaded into suitable blender and blended for 15 minutes and is added to Fluid bed processor, mixed for 5 min.

4. Eudragit NM30D was added to above step and granules were prepared.

5. Prepared granules were dried and sifted through mesh #60.

Extra-granular:

6. Microcrystalline cellulose, F-Melt Type C, Crospovidone, Sodium starch glycolate and aspartame were sifted through mesh #30 separately.

7. Dried granules of dolutegravir were co-sifted with microcrystalline cellulose through mesh #30.

8. The above material is co-sifted with F-Melt Type C, Crospovidone, Sodium starch glycolate and aspartame and sifted through mesh #30.

9. Magnesium stearate was sifted through mesh #30 and added to the above material and lubricated.

Compression:

10. The lubricated blend is compressed into tablets using suitable tooling.
Dissolution data:

Dissolution test was performed for tablets prepared as per the examples 5 and 6 using USP apparatus II, 50 rpm, in 900 ml of 0.01M pH 6.8 phosphate buffer containing 0.5% w/v sodium dodecyl sulfate (SDS).

Time (Min) % Drug Released
Innovator (Tivicay) 10mg (Ex. 5) 5mg (Ex. 6)
5 70 36 35
10 86 57 61
15 92 71 76
30 97 89 91
45 99 95 95
60 99 97 96

Dispersible tablets of Dolutegravir sodium compositions as per example 5 and 6, exhibit dissolution profile of more than 85% within 30 min which is comparable to innovator product.
Disintegration time for Dolutegravir tablets 10mg prepared from Ex.5:
Time period Initial 40°C / 75%RH
1 Month 3 Months 6 Months
Disintegration time (min) 55 sec to
1 min 05 sec 1 min 20 sec to
1 min 25 sec 1 min 40 sec to
1 min 50 sec 2 min 05 sec to
2 min 15 sec

Results of stability evaluation of Dolutegravir tablets 10mg prepared from Ex.5
Time Period Initial 40°C / 75%RH
1 Month 3 Months 6 Months
Time (Min) % Drug Released
5 36 28 31 27
10 57 52 54 49
15 71 67 69 64
30 89 86 86 82
45 95 91 90 88
60 97 93 92 90

Disintegration time for Dolutegravir tablets 5mg prepared from Ex.6:

Time period Initial 40°C / 75%RH
1 Month 3 Months 6 Months
Disintegration time (min) 45 sec to
55 sec 1 min 15 sec to
1 min 25 sec 1 min 30 sec to
1 min 45 sec 2 min to
2 min 15 sec

Results of stability evaluation of Dolutegravir tablets 5mg prepared from Ex.6.
Time Period Initial 40°C / 75%RH
1 Month 3 Months 6 Months
Time (Min) % Drug Released
5 35 31 37 37
10 61 56 56 59
15 76 71 70 72
30 91 87 91 90
45 95 92 99 97
60 96 94 104 100

Dolutegravir dispersible tablets prepared as per Example 5 and Example 6 were found to have similar disintegration and dissolution profile after 6 months of storage at 40°C / 75%RH.

,CLAIMS:WE CLAIM:

1. A dispersible tablet composition comprising 5 mg - 10 mg of dolutegravir having d90 particle size less than 50µm and at least one pharmaceutically acceptable excipient.

2. The dispersible tablet composition of claim 1, wherein the composition disintegrates in water within 3 minutes.

3. The dispersible tablet composition of claim 1, wherein the composition shows dissolution of more than 60% within 30 minutes.

4. A dispersible tablet composition comprising 0.1- 30% of dolutegravir sodium having d90 particle size less than 50µm, 10-80% of diluent, 5-30% of disintegrant, 0.5-10% of binder, 0.5-3.0% of lubricant and 0.1 to 3.0% of sweetener by total weight of the composition, wherein the composition disintegrates in water within 3 minutes and composition shows dissolution of more than 80% within 30 minutes.

5. A dispersible tablet composition comprising:
i. 2 - 5 % of Dolutegravir sodium,
ii. 3 – 40 % of Microcrystalline cellulose,
iii. 5 – 80 % of Mannitol,
iv. 7 – 25 % of Crospovidone,
v. 3 – 15 % of anhydrous dibasic calciul phosphate,
vi. 1 – 6 % of Xylitol,
vii. 0.1 – 5 % of Sodium starch glycolate,
viii. 0.5 – 2 % of Povidone,
ix. 1 – 10 % of Ethyl Acrylate and Methyl Methacrylate Copolymer,
x. 0.5 - 2 % of Aspartame, and
xi. 0.5 – 3 % of Magnesium stearate.

6. The dispersible tablet composition of claim 1, is prepared by wet granulation process.

7. The composition of claim 1, is for use in the pediatric and/or geriatric population.

Dated this Twenty-Fifth (25th) day of July, 2019

Signature: ----------------------------------------------------------
Name: Dr. KHADGAPATHI PODILE
EXECUTIVE DIRECTOR
HETERO LABS LIMITED