DESC:FIELD OF THE INVENTION

The present invention relates to a pharmaceutical composition comprising vilazodone or its pharmaceutically acceptable salts, wherein the blend uniformity of the said composition is between 95% and 105%. Further it relates to the process for the preparation of the said composition and uses thereof.

BACKGROUND OF THE INVENTION

Vilazodone is a selective serotonin reuptake inhibitor and a 5HT1A receptor partial agonist. The IUPAC name of Vilazodone HCl is 2-benzofurancarboxamide, 5-[4-[4-(5cyano-1H-indol-3-yl)butyl]-1-piperazinyl]-,hydrochloride (1:1). The chemical structure is shown in formula below:

Vilazodone is disclosed in U.S. Patent Nos. 5,532,241, which describe the compound and its pharmaceutical compositions. U.S. Patent No. 7,834,020; 8193195 and 8,236,804 discloses the polymorphic forms of vilazodone HCl and its use for the treatment of patients suffering from major depressive disorder.

Currently, Vilazodone HCl (VIIBRYD®) is available as 10 mg, 20 mg and 40 mg immediate-release film-coated Tablets, which contains the polymorphic form-IV of vilazodone HCl.

Several attempts have been made in the prior art to develop an amorphous form of Vilazodone HCl and its pharmaceutical compositions. Published patent applications such as WO2012131706, WO2013088373 and US20130324554 disclose the amorphous form of vilazodone HCl and its preparations thereof.

However, the prior art formulations does not provide blend uniformity and content uniformity of pharmaceutical compositions, particularly when prepared with an amorphous form of vilazodone hydrochloride.

Hence, there is a long-standing need to provide a pharmaceutical composition comprising amorphous form of vilazodone hydrochloride with blend uniformity and better compressibility.

OBJECTS OF THE INVENTION

The primary object of the invention is to provide a pharmaceutical composition comprising vilazodone hydrochloride, wherein the blend uniformity of the said composition is between 95% and 105% and the relative standard deviation (RSD) of the said composition is less than 2%.

Another object of the invention is to provide a pharmaceutical composition comprising vilazodone hydrochloride, wherein the tablet hardness is at least 50 N.

Another object of the invention is to provide a pharmaceutical composition comprising vilazodone hydrochloride and silicified microcrystalline cellulose.

Another object of the invention is to provide a pharmaceutical composition comprising vilazodone hydrochloride, wherein the said composition is prepared by direct compression method.

SUMMARY OF THE INVENTION

In a first embodiment, the invention relates to a pharmaceutical composition comprising amorphous form of vilazodone hydrochloride, wherein the blend uniformity of the said composition is between 95% and 105% and the relative standard deviation (RSD) of the said composition is less than 2%.

In a preferred embodiment, the invention relates to a pharmaceutical composition comprising amorphous form of vilazodone hydrochloride, wherein the tablet hardness is at least 50 N.

In a preferred embodiment, the invention relates to a pharmaceutical composition comprising amorphous form of vilazodone hydrochloride and silicified microcrystalline cellulose.

In another embodiment, the invention relates to a pharmaceutical composition comprising amorphous form of vilazodone hydrochloride, wherein the said composition is prepared by direct compression method.

DETAILED DESCRIPTION

The present invention relates to a pharmaceutical composition comprising amorphous form of vilazodone hydrochloride, wherein the blend uniformity of the said composition is between 95% and 105% and the relative standard deviation (RSD) of the said composition is less than 2%.

The prior art formulations does not provide blend uniformity and content uniformity, particularly when prepared with an amorphous form of vilazodone hydrochloride. The inventors of the present invention have surprisingly found a pharmaceutical composition comprising amorphous form of vilazodone hydrochloride, wherein the blend uniformity of the said composition is between 95% and 105%, with the use of directly compressible co-processed excipients.

In particular, the present invention relates to a pharmaceutical composition comprising amorphous form of vilazodone hydrochloride and silicified microcrystalline cellulose.

Not bound to any theory, the term "blend uniformity," as used herein, refers to the homogeneity of blend before converting into finished dosage form, e.g. pharmaceutical compositions such as tablets. The blend uniformity of the lubricated blend samples can be determined by the conventional techniques known in the art.

Not bound to any theory, the term "Content uniformity," as used herein, refers to the homogeneity of the drug content among individual units of finished dosage form, e.g. pharmaceutical compositions such as tablets.

Not bound to any theory, the term "Relative standard deviation" or "RSD," as used herein, refers to a measurement of how precise each measurement of content uniformity is, i.e., how much each individual unit deviates from the group with regards to the drug content. Preferably, the relative standard deviation of vilazodone tablets is less than 2%. The relative standard deviation can be determined by the conventional techniques known in the art.

The present invention may comprise any pharmaceutically acceptable form of vilazodone, including its pharmaceutically acceptable salts. In particular, the present invention uses amorphous form of vilazodone hydrochloride.

The excipient “silicified MCC” refers to co-processed excipient comprising micro-crystalline cellulose and silicon dioxide. Preferably, the silicified MCC is a combination comprising 98% microcrystalline cellulose and 2% colloidal silicon dioxide. The silicified MCC possess bulk density between 0.38 to 0.50 gm/ml and particle size distribution with D10 between 20 to 70 µm, D50 between 90 to 160 µm, D90 between 160 to 320 µm.

The compositions of the present invention when comes in contact with gastric fluid it readily disintegrates and provide an immediate release of the drug within body.

In addition to the above-mentioned ingredients, the compositions of the present invention may also comprise further pharmaceutically acceptable excipients such as diluents, binders, disintegrants, lubricants, wetting agent, glidants, coating excipients and the like.

The said pharmaceutically acceptable excipients can be used for the purpose of the compositions of the present invention, such that the resulting pharmaceutical compositions comprising amorphous form of vilazodone hydrochloride possess blend uniformity and superior compressibility.

Preferably, the pharmaceutically acceptable excipients include lactose, mannitol, Sodium Starch Glycolate, Crospovidone XL10, Magnesium Stearate and the like.

In another embodiment, the invention relates to a process for the preparation of pharmaceutical compositions of vilazodone hydrochloride. It can be prepared by routine tableting method including direct compression, granulation and pelletization methods. Preferably, the process for the preparation is direct compression method.

In order to further illustrate the present invention, the following examples are provided for the purpose of clarity of understanding. However, it is not intended in any way to limit the scope of present invention and it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the scope of the invention.

Example 1: Pharmaceutical compositions of Vilazodone.
F1 F2 F3
Ingredients %w/w core %w/w core %w/w core
Vilazodone HCl (Amorphous) 10% 10% 10%
Silicified MCC 69% 59% 10%
Lactose Monohydrate 15% 15% -
Mannitol (Pearlitol SD 200) - - 64%
Sodium Starch Glycolate 5% - -
Crospovidone XL10 - 15% 15%
Magnesium Stearate 1% 1% 1%
Core Tablet Weight 100% 100% 100%
Film Coating q.s. q.s. q.s.

The pharmaceutical composition of the present invention is prepared by direct compression method in the procedural steps as described below.

Manufacturing Process:
(i) Sift all ingredients through appropriate sieves,
(ii) Blend the sifted ingredients for an appropriate time,
(iii) Compressed the blend into tablets
(iv) Optionally, film coat on the compressed tablets.

Example 2: Blend uniformity study of lubricated blend of Vilazodone HCl.
Batch Number Blend uniformity of Lubricated Blend Samples* Mean (%) % RSD
S1 S2 S3 S4 S5 S6 S7 S8 S9 S10
F1 100.6 99.5 98.4 96.6 97.7 98.5 98.5 99.6 98.8 99.2 98.7 1.1
F2 99.6 100.4 100.1 101.2 100.2 100.7 99.8 99.6 99.8 100.1 100.2 0.5
F3 100.6 100.5 100.4 99.3 100.0 100.7 100.0 100.2 100.0 99.9 100.2 0.4

* S1-S10 represents lubricated blend samples of Vilazodone HCl.
* Acceptable limits of blend uniformity of the samples: 95.0% to 105.0%.
* Acceptable Relative standard deviation (RSD): Not more than 5.0%
,CLAIMS:1. A pharmaceutical composition comprising vilazodone hydrochloride, wherein the blend uniformity of the lubricated blend, used for the preparation of the said composition is between 95% and 105%.

2. A pharmaceutical composition comprising vilazodone hydrochloride, wherein the relative standard deviation of the said composition is less than 2%.

3. The pharmaceutical composition according to any of the preceding claims, wherein the lubricated blend comprises vilazodone HCl and silicified microcrystalline cellulose with pharmaceutically acceptable excipients.

4. The pharmaceutical composition according to any of the preceding claims, wherein the pharmaceutical composition is a tablet comprising vilazodone hydrochloride.

5. The pharmaceutical composition according to any of the preceding claims, wherein the hardness of vilazodone hydrochloride tablet is at least 50 N.

6. The pharmaceutical composition according to any of the preceding claims, wherein the pharmaceutical composition comprises amorphous form of vilazodone hydrochloride.

7. The pharmaceutical composition according to any of the preceding claims, wherein the pharmaceutical composition is prepared by direct compression method.

8. A lubricated blend comprising amorphous vilazodone hydrochloride and silicified microcrystalline cellulose with pharmaceutically acceptable excipients, wherein the blend uniformity is between 95% and 105%.

9. A pharmaceutical composition comprising amorphous vilazodone hydrochloride and silicified microcrystalline cellulose with pharmaceutically acceptable excipients, wherein the relative standard deviation of the said composition is less than 2%.