DESC:The present invention provides a modified release composition of Viloxazine HCl comprising:

a. first drug layer applied to the inert core comprising Viloxazine HCl with at least one pharmaceutically acceptable binder and /or film forming agent to provide a drug coated pellet,
b. second layer applied on the drug coated pellet using one or more rate-controlling polymers to provide an Extended-release coated pellet,

c. a third layer comprising Viloxazine HCl on the Extended release coated pellet with at least one pharmaceutically acceptable excipient(s),

d. a fourth film coating layer applied on the Extended-release pellet with at least one pharmaceutically acceptable excipient(s),

According to the one embodiment of the present invention, binder and /or film forming agent is selected from the group consisting of hydroxypropyl cellulose; hydroxypropyl methyl cellulose; methyl cellulose; polyethylene oxide; acacia; acrylic acid derivatives; alginic acid, its salts and derivatives thereof; hydroxyethyl cellulose; povidone; carrageenan; carboxymethylcellulose; tragacanth; polyvinyl alcohol; xanthan gum, and combinations thereof.

According to the second embodiment of the present invention, release rate controlling compound is selected from the group consisting of ethyl cellulose; cellulose acetate; cellulose acetate butyrate; polyvinyl acetate; cellulose acetate propionate, and combinations thereof.

According to the third embodiment of the present invention, the disclosed composition comprises at least three to four layers of coatings on core pellets, extrudes and / or mini tablets.

According to the fourth embodiment of the present invention, dosage form is selected from tablets, capsules, beads, granules, powders, caplets, troches, sachets, cachets, pouches, and sprinkles.

According to the fifth embodiment of the present invention, at least one extended-release component, wherein the extended-release component has its own rate of release.

According to another embodiment, the modified release composition of Viloxazine HCl includes, dispersing agents, glidants, plasticizers, lubricants, surfactants, disintegrants, film coating agents and coloring agents. As understood by a person skilled in the art, these excipients are conventional excipients which are well known in the pharmaceutical art.

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.

The present invention can be illustrated in one of its embodiments by the following non- limiting examples.

EXAMPLES

Example 1: Fluid bed coating process
S. No Ingredients mg / cap % w/w
1 Sugar spheres 25# / 30# 180.00 34.22
Drug layer - 1 (Extended-release portion)
2 Viloxazine HCl 184.75 35.12
3 Hypromellose E5 27.75 5.28
4 PEG 6000 2.50 0.48
5 Purified water ¥ q.s. NA
Weight of drug loaded pellets 395.00 NA
Extended-release coating
6 Ethyl cellulose 10 cps 24.00 4.56
7 Hypromellose E 5 11.00 2.09
8 Triethyl Citrate 2.50 0.48
9 Purified talc 2.50 0.48
10 IPA q.s. NA
11 Purified water ¥ q.s. NA
Weight of extended release coated pellets 435.00 NA
Drug layer - 2 (Immediate release portion)
12 Viloxazine HCl 46.00 8.75
13 Hypromellose E5 8.00 1.52
14 PEG 6000 1.00 0.19
15 Purified water ¥ q.s. NA
Weight of drug layer-2 coated pellets 490.00 NA
Film coating
16 Hypromellose E 5 28.00 5.32
17 Polyethylene glycol 6000 3.00 0.57
18 Titanium dioxide 2.50 0.48
19 Purified talc 2.50 0.48
20 Purified water ¥ q.s. NA
Weight of FINAL pellets 526.00 100.00

The processing steps involved in manufacturing are given below:
1. Viloxazine HCl was loaded (Extended-release portion) to the sugar pellets using Purified water along with HPMC E5. PEG 6000 and Purified talc.
2. Extended-release coating to the drug loaded pellets was carried with HPMC E 15 and Ethyl cellulose in Isopropyl alcohol and water. The other ingredients used in extended-release coating are Triethyl citrate and Purified Talc.
3. Viloxazine HCl drug was loaded (immediate release portion) to the Extended release coated pellets using Purified water along with HPMC E5, PEG 6000 and Purified talc.
4. The Film coating to the Viloxazine HCl pellets used HPMC E5, PEG 6000 and talc.
5. the film coated pellets were filled into hard gelatin capsules using capsule filling machine.

Note: The strengths 200mg, 150mg and 100mg are dose weight proportional.

Dissolution profile in pH 6.8 phosphate buffer (50mM Potassium phosphate), 900ml, Paddle with 50 RPM.

Example 2A: Extrusion, Spheronization and followed by Fluid bed coating process
S. No Raw material name gm / kg % w/w
1 Microcrystalline cellulose 101 160.00 30.42
2 Viloxazine HCl 184.75 35.12
3 Ethyl cellulose 10 cps 58.00 11.03
4 Hypromellose E 15 32.00 6.08
5 Purified talc 5.25 1.00
6 IPA q.s. NA
7 Purified water ¥ q.s. NA
Weight of extended-release pellets 440.00 NA

8 Viloxazine HCl 46.00 8.75
9 Hypromellose E5 8.00 1.52
10 PEG 6000 1.00 0.19
11 Purified water ¥ q.s. NA
Weight of IR drug layer coated pellets 495.00 NA

12 Hypromellose E 5 23.00 4.37
13 Polyethylene glycol 6000 3.00 0.57
14 Titanium dioxide 2.50 0.48
15 Purified talc 2.50 0.48
16 Purified water ¥ q.s. NA
Weight of FINAL pellets 526.00 100.00

The processing steps involved in manufacturing are given below:
1. A wet granular mass of Viloxazine HCl (Extended-release portion) was prepared with Microcrystalline cellulose, HPMC E15, Ethyl cellulose and Purified talc using Isopropyl alcohol and water in Rapid mixer granulator.
2. the prepared wet mass was subjected to extrusion through extruder fitted with 1mm screen.
3. the extrudes are subjected to spheronization and the spheroidal pellets were dried using flid bed drier.
4. Viloxazine HCl was loaded (immediate release portion) to the Extended-release pellets (prepared by extrusion and spheronization process) using Purified water along with HPMC E5, PEG 6000 and Purified talc.
5. the Viloxazine HCl pellets were film coated using HPMC E5, PEG 6000 and talc.
6. the film coated pellets were filled into hard gelatin capsules using capsule filling machine.

Example 2B: Extrusion, Spheronization and followed by Fluid bed coating process
S. No Raw material name gm / kg % w/w
1 Microcrystalline cellulose 101 170.00 32.32
2 Viloxazine HCl 184.75 35.12
3 Eudragit NE 30 D 46.00 8.75
4 Hypromellose E 15 30.00 5.70
5 Mannitol 10.00 1.90
6 Purified talc 4.25 0.81
8 Purified water ¥ q.s. NA
Weight of extended-release pellets 445.00 NA

9 Viloxazine HCl 46.00 8.75
10 Hypromellose E5 8.00 1.52
11 PEG 6000 1.00 0.19
12 Purified water ¥ q.s. NA
Weight of IR drug layer coated pellets 500.00 NA

13 Hypromellose E 5 19.00 3.61
14 Polyethylene glycol 6000 2.00 0.38
15 Titanium dioxide 2.50 0.48
16 Purified talc 2.50 0.48
17 Purified water ¥ q.s. NA
Weight of FINAL pellets 526.00 100.00

Brief Manufacturing Process:
The processing steps involved in manufacturing are given below:
1. a wet granular mass of Viloxazine HCl (Extended-release portion) was prepared with Microcrystalline cellulose, HPMC E15, Eudragit NE 30 D, Mannitol and Purified talc using water in Rapid mixer granulator.
2. the prepared wet mass passed through extruder fitted with 1mm screen.
3. the extrudes were spheronized and the spheroidal pellets were dried using flid bed drier.
4. Viloxazine HCl (immediate release portion) was loaded to the Extended release pellets (prepared by extrusion and spheronization process) using Purified water along with HPMC E5, PEG 6000 and Purified talc.
5. the Viloxazine HCl pellets were film coated using HPMC E5, PEG 6000 and talc.
6. the film coated pellets were filled into hard gelatin capsules using capsule filling machine.

Dissolution profile in pH 6.8 phosphate buffer (50mM Potassium phosphate), 900ml, Paddle with 50 RPM.

Example 3: Mini tablets for capsule filling
S. No Raw material name Mg / per tab % w/w
1 Microcrystalline cellulose 101 17.00 22.67
2 Viloxazine HCl 30.80 41.07
3 Eudragit NE 30 D 7.00 9.33
4 Hypromellose E 15 3.00 4.00
5 Mannitol 1.00 1.33
6 Purified talc 0.50 0.67
7 Magnesium stearate 0.70 0.93
8 Purified water ¥ q.s. NA
Weight of extended-release pellets 60.00 NA

9 Viloxazine HCl 7.68 10.24
10 Hypromellose E5 2.17 2.89
11 PEG 6000 0.15 0.20
12 Purified water ¥ q.s. NA
Weight of IR drug layer coated pellets 70.00 NA

13 Hypromellose E 5 4.00 5.33
14 Polyethylene glycol 6000 0.40 0.53
15 Titanium dioxide 0.40 0.53
16 Purified talc 0.20 0.27
17 Purified water ¥ q.s. NA
Weight of tablet wt 75.00 100.00

The processing steps involved in manufacturing are given below:
1. Mini tablets of Viloxazine HCl (Extended-release portion) were prepared with Microcrystalline cellulose, HPMC E15, Eudragit NE 30 D, Mannitol, Magnesium stearate and Purified talc using water by wet granulation followed by mini tablet compression.
2. Viloxazine HCl (immediate release portion) was loaded to the Extended release tablets (prepared by wet granulation process) using Tablet auto-coater along with HPMC E5, PEG 6000 and Purified talc.
3. the Viloxazine HCl mini tablets were film coated with HPMC E5, PEG 6000 and talc using tablet auto-coater.
4. the film coated mini pellets were filled into hard gelatin capsules using capsule filling machine.

Dissolution profile in pH 6.8 phosphate buffer (50mM Potassium phosphate), 900ml, Paddle with 50 RPM.

,CLAIMS:WE CLAIM:

1. A modified release pharmaceutical composition of Viloxazine HCl comprising:

(a) first drug layer applied to the inert core comprising Viloxazine HCl with at least one pharmaceutically acceptable binder and /or film forming agent to provide a drug coated pellet,
(b) a second layer applied on the drug coated pellet using one or more rate-controlling polymers to provide an Extended-release coated pellet,
(c) a third layer comprising Viloxazine HCl on the Extended release coated pellet with at least one pharmaceutically acceptable excipient(s),
(d) a fourth film coating layer applied on the Extended-release pellet with at least one pharmaceutically acceptable excipient(s).

2. The modified release composition according to claim 1, the binder and /or film forming agent is selected from the group comprising of hydroxypropyl cellulose; hydroxypropyl methyl cellulose; methyl cellulose; polyethylene oxide; acacia; acrylic acid derivatives; alginic acid, its salts and derivatives thereof; hydroxyethyl cellulose; povidone; carrageenan; carboxymethylcellulose; tragacanth; polyvinyl alcohol; xanthan gum, and combinations thereof.

3. The modified release composition according to claim 1, the release rate controlling agent is selected from the group comprising of ethyl cellulose; cellulose acetate; cellulose acetate butyrate; waxes; hydrogenated vegetable oils; glyceryl behenate; glyceryl palmitostearate; PEG glyceryl esters; poly(ethyl acrylate-co-methyl methacrylate) ethyl acrylate methyl methacrylate copolymer; poly( ethyl acrylate-co-methyl methacrylate-cotrimethylanimonioethyl methacrylate chloride);polyvinyl acetate; cellulose acetate propionate, and combinations thereof.

4. The modified release composition according to claim 1, comprises at least three to four layers of coatings on core pellets, extrudes and / or mini tablets.

5. The modified release composition according to claim 1, the dosage form is selected from tablets, capsules, beads, granules, powders, caplets, troches, sachets, cachets, pouches, and sprinkles.

6. The modified release composition according to claim 1, comprises at least one extended-release component, wherein the extended-release component has its own rate of release.