DESC:DESCRIPTION OF THE INVENTION

The present invention relates to methods, pharmaceutical compositions comprising of Fluvoxamine or its pharmaceutically acceptable salts, and/or solvates, and/or esters, and/or polymorphs, and/or hydrates, and/or amides, and/or chelates, and/or complexes and/or prodrugs.

The present invention relates to methods, pharmaceutical compositions comprising of Fluvoxamine or its pharmaceutically acceptable salts, and/or solvates, and/or esters, and/or polymorphs, and/or hydrates, and/or amides, and/or chelates, and/or complexes and/or prodrugs and methods useful for the treatment of depression or obsessive-compulsive disorder.

For the purpose of the present invention as disclosed and described herein, the following terms and abbreviations are defined as follows.

The term “Pharmaceutical composition”as used herein, includes topical oral, parenteral composition of Fluvoxamine.

The term "composition of Fluvoxamine", as used herein, includes Pharmaceutical or cosmetic composition comprising of Fluvoxamine or its pharmaceutically acceptable salts, and/or solvates, and/or esters, and/or polymorphs, and/or hydrates, and/or amides, and/or chelates, and/or complexes and/or prodrugs.

The composition comprising Fluvoxamine is in the range of 25 mg to 200 mg of the total composition.

The composition comprising Fluvoxamine is in the range of 25 mg to 200 mg of the total composition is administered orally.

The composition comprising Fluvoxamine is in the range of 25 mg to 200 mg of the total composition is administered once daily to thrice daily.

The term "pharmaceutically acceptable" means approved by a regulatory agency of the Federal or state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more particularly in humans.

The term "pharmaceutically acceptable salt" refers to those salts of Fluvoxamine which are, within the scope of sound medical evaluation, suitable for use in contact with the tissues and organs of humans and lower animals without displaying toxicity, irritation, allergic response and the like and are commensurate with a reasonable benefit/risk ratio.

The term "pharmaceutically acceptable carrier, vehicle or excipient" as used here, means a solid, semi-solid or inert fluid excipient, filler, encapsulating or formulation aiding material of any kind already known by one skilled in the art.

The term “oral” as used herein refers to delivery of a compound by mouth such that the compound passes through the oral mucosa, stomach, small intestine, or large intestine into the systemic circulation.

The term "treatment of" as used herein, means abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetical symptoms of a condition or substantially preventing the appearance of clinical or aesthetical symptoms of a condition.

The term "comprising" as used herein, means that other steps and ingredients that do not affect the final result can be added. This term encompasses the terms "consisting of and "consisting essentially of.

The phrase "consisting essentially of” as used herein, means the composition or method may include additional ingredients and/or steps, but only if the additional ingredients and/or steps do not materially alter the basic and novel characteristics of the claimed composition or method.

The term "method" as used herein, means manners, means, the techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and

procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts, know techniques for the manufacture of finished dosage form.

The term "therapeutically effective amount" or "pharmaceutically effective amount" as used herein, means the dose of an active ingredient or a composition comprising the active ingredient that will provide the therapeutic effect for which the active ingredient is indicated.

The present invention is an extended release pharmaceutical composition comprising
i. 1-70% w/w of fluvoxamine maleate,
ii. an extended release polymer is combination of hypromellose and ethyl cellulose or hydroxy propyl cellulose and ethyl cellulose
iii. less than 25% w/w of mannitol and
iv. one or more pharmaceutically acceptable carries
wherein the composition is compressed mini tablets filled into capsule, provided the composition does not contain starch & microcrystalline cellulose.
The extended release composition of the present invention comprises pharmaceutical acceptable carrier is selected from diluent, binder, solvents, glidant, lubricant and Plasticizer.
The present invention comprises suitable fillers or diluents, disintegrants, glidants and lubricants are known to those of skill in the art.
Preferable diluents include lactose, maltodextrin, mannitol, microcrystalline cellulose, pregelatinized starch, and sucrose esters.
Useful flow enhancers, glidants include colloidal silicon dioxide, talc, magnesium stearate, and mannitol.
Useful lubricants include magnesium stearate, calcium stearate, glyceryl monostearate, hydrogenated castor oil, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, zinc stearate, talc, microcrystalline cellulose, and sucrose esters.
The preferred suitable extended release polymers are hypromellose, hydroxy propyl cellulose and ethyl cellulose and their combinations thereof.

The preferred suitable solvents are known to those of skill in the art and preferably purified water or Iso propyl alcohol.

The preferred suitable glidants are known to those of skill in the art and preferably silicon dioxide.

The preferred suitable lubricant is known to those of skill in the art and preferably sodium stearyl fumarate.

The preferred suitable lubricant is known to those of skill in the art and preferably triethyl citrate.

The extended release composition of the present invention further comprises coating.

Example 1: Tablet Filled into capsule – Direct Compression
Excipient
Fluvoxamine Maleate
Mannitol
PGS
Starch NF
Silicon Dioxide NF
Sodium Stearyl fumarate
Core Tablet Weight
Polymer Coating
Ethyl Cellulose
TEC
Hypromellose
Povidone
IPA
Water
Total Tablet Weight

Example 2: Tablet Filled into capsule – Wet granulation
Excipient
Fluvoxamine Maleate
Mannitol
PGS
Starch NF
Silicon Dioxide NF
Sodium Stearyl fumarate
Water
Core Tablet Weight
Polymer Coating
Ethyl Cellulose
TEC
Hypromellose
Povidone
IPA
Water
Total Tablet Weight

Example 3: Fluvoxamine ER Capsule
Name of the Ingredient % w/w
Dry mix Material
Fluvoxamine maleate 63.56
Mannitol 23.52
Hypromellose 1.59
Binder solution
Hypromellose 1.59
Purified water Qs
Extragranular Material
Silicon dioxide 2.54
Sodium stearyl fumarate 2.54
Coating Material
Ethyl cellulose 3.18
Hypromellose 1.06
Triethyl citrate 0.42
IPA Qs
Total tablet weight 100

Example 4: Fluvoxamine ER Capsule
Name of the Ingredient % w/w
Dry mix Material
Fluvoxamine maleate 63.56
Mannitol 23.52
Hypromellose 1.59
Binder solution
Hypromellose 1.59
Purified water Qs
Extragranular Material
Silicon dioxide 2.54
Sodium stearyl fumarate 2.54
Coating Material
Ethyl cellulose 3.18
Hydroxy propyl cellulose 1.06
Triethyl citrate 0.42
IPA Qs
Total tablet weight 100
Manufacturing Process:
Step 1: Sifting
Step 2: Granulation
Step 3: wet milling
Step 4: Drying
Step 5: Milling
Step 6: Blending

Step 7: Lubrication
Step 8: Mini tablet Compression
Step 9: Encapsulation

Example 5: Figure 4: Dissolution data of examples

Example 6: Table 1: Stability data of examples
Product name Fluvoxamine Maleate ER Capsules
Pack HDPE Bottle
Stability Condition RT 40 ºC/75%RH 6M
Test Specification
Assay(%) 95-105% 100.5 102.1
Dissolution pH 6.8; Apparatus Usp type II (paddle);RPM : 50; volume: 900 ml
1 hr NMT40% 18 23
3 hr 65-90% 67 67
12 hr NLT80% 101 98

,CLAIMS:We claim:
1. An extended release pharmaceutical composition comprising
v. 1-70% w/w of fluvoxamine maleate,
vi. an extended release polymer is combination of hypromellose and ethyl cellulose or hydroxy propyl cellulose and ethyl cellulose
vii. less than 25% w/w of mannitol and
viii. one or more pharmaceutically acceptable carries
wherein the composition is compressed mini tablets filled into capsule, provided the composition does not contain starch & microcrystalline cellulose.
2. The extended release composition as claimed in claim 1, wherein the pharmaceutical acceptable carrier is selected from diluent, binder, solvents, glidant, lubricant and Plasticizer.
3. The extended release composition as claimed in claim 3 where in the diluent is mannitol.
4. The extended release composition as claimed in claim 3 where in the binder is hypromellose (HPMC).
5. The extended release composition as claimed in claim 3 where in the solvent is purified water or Iso propyl alcohol.
6. The extended release composition as claimed in claim 3 where in the glidant is silicon dioxide.
7. The extended release composition as claimed in claim 3 where in the lubricant is sodium stearyl fumarate.
8. The extended release composition as claimed in claim 3 where in the plasticizer is tiethyl citrate.
9. The extended release composition as claimed in claim 1 further comprises coating.