Field of the Invention:
The present invention relates to pharmaceutical composition of moxifloxacin, its salts and/or hydrates and also relates to the method of preparation of the pharmaceutical composition.
Furthermore, the present invention provides a process for preparing tablets which comprise such preparations.
Background of the invention
Moxifloxacin is chemically known as l-cyclopropyl-7-([S,S]-2,8-diazabicyclo
[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolonecarboxylic acid
(formula-1).

Moxifloxacin is an effective anti-infective agent which can be used for the treatment of various infections, like acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and community acquired pneumonia. It is also used in the treatment of tuberculosis. Moxifloxacin hydrochloride tablets are marketed under the brand name of Avelox by Bayer.
Moxifloxacin and its related compounds were reported in U.S. Patent No. 4,990,517. The patent also discloses a pharmaceutical preparation that includes the moxifloxacin, with microcrystalline cellulose, maize starch, poly-(l-vinyl)2-pyrrolidone (insoluble), finely divided silica and magnesium stearate.
Moxifloxacin hydrochloride monohydrate was reported in U.S. Patent No. 5,849,752. This patent also discloses a pharmaceutical preparation that includes the

moxifloxacin hydrochloride monohydrate, with microcrystalline cellulose, maize starch, PVP-25, crascormellose sodium and magnesium stearate. This patent does not explain specific advantages by using this composition.
U.S. Patent No. 6,610,327 discloses pharmaceutical preparations for oral administration that includes moxifloxacin or a salt or a solvate/hydrate thereof, at least one dry binder, at least one disintegrant and at least one lubricant, characterized in that the preparation contains 2.5 to 25% of lactose. It has been disclosed that the use of 2.5 to 25% of lactose in the composition improved the hardness or breaking load of the tablet formulation. Though there was an improvement in these properties, they were not substantial enough as desired.
WO 2005/020998 discloses pharmaceutical preparation that includes moxifloxacin and at least one intragranular and extragranular substantially water insoluble excipients.
US 6610327 provides pharmaceutical preparations for oral administration which comprise moxifloxacin, at least one dry binder, at least one disintegrant and optionally a lubricant, characterized in that the preparation comprises from 2.5% to 25% of lactose. But there was still scope for improvement in the properties of the pharmaceutical compositions described above.
It was observed that the further increase in the concentration of lactose improved the properties like hardness of the tablets or the breaking load. Hence in the present invention a pharmaceutical composition was prepared using 26-50% of lactose with a combination of at least one wet binder which not only gave substantial enhancement in hardness or breaking load of the tablet but also provided improved release properties. One of the formulations utilizes povidone which has greater viscosity and adhesive properties improve the overall quality of the pharmaceutical composition.

Summary of the invention:
The present invention relates to phannaceutical composition of moxifloxacin, its salts and/or hydrates and also relates to the method of preparation of the pharmaceutical composition.
First aspect of this invention provides a pharmaceutical composition of moxifloxacin, its salts and/or hydrate which consists of lactose in a concentration of above 26%, along with at least one disintegrant, a glidant and a lubricant.
Second aspect of the present provides a pharmaceutical composition of moxifloxacin, its salts and/or hydrate comprising the active substance in combination with water soluble diluent especially mannitol, at least one wet binder, at least one disintegrant, a glidant and a lubricant.
The third aspect of this invention provides a pharmaceutical composition of moxifloxacin, its salts and/or hydrate which consists of lactose in a concentration of above 26%, along with one wet binder especially povidone, at least one disintegrant, a glidant and a lubricant.
Furthermore, the present invention provides a process for preparing tablets which comprise such preparations.
Detailed Description of the invention:
The present invention relates to pharmaceutical composition of moxifloxacin, its sahs and/or hydrates and also relates to the method of preparation of the pharmaceutical composition. Furthermore, the present invention provides a process for preparing tablets which comprise such preparations.
As used herein moxifloxacin refers its free base, salts, solvates, enantiomers or mixtures thereof The salts of moxifloxacin include, for example, acid addition salts, such as sahs of hydrochloric acid, sulphuric acid, acetic acid, lactic acid, etc. In particular, the acid addition salt is moxifloxacin hydrochloride monohydrate.

The formulation according to the invention preferably comprises from 50 to 80%, particularly preferably from 60 to 75%, of moxifloxacin or salts and/or hydrates thereof (all the percentages are % by weight based on the weight of the pharmaceutical preparation).Based on the individual dose, the pharmaceutical preparation comprises generally from 50 to 800 mg of moxifloxacin, preferably from 100 to 600 mg, particularly preferably from 200 to 400 mg.
The first aspect of the present invention provides a pharmaceutical preparation of moxifloxacin, its salts and/or hydrates which preferably comprises of lactose in a concentration of 26 to 50%, along with at least one disintegrant, a glidant and a lubricant.
Second aspect of the present provides a pharmaceutical composition of moxifloxacin, its salts and/or hydrate comprising the active substance in combination with water soluble diluent especially mannitol, at least wet binder, at least one disintegrant, a glidant and a lubricant.
The third aspect of this invention provides a pharmaceutical preparation of moxifloxacin, its salts and/or hydrate which consists of lactose in a concentration of above 26%, along with wet binder povidone, at least one disintegrant, a glidant and a lubricant.
The pharmaceutical preparation comprises, as components which are essential for achieving the object according to the invention, from 26 to 50% of lactose, preferably form 28 to 45% of lactose and particularly preferably from 30 to 35% of lactose. The lactose used can be intra-granular as well as inter-granular.
According to the present invention the wet binder is selected from the group consisting of: com starch, polyvinyl pyrrolidone (povidone), vinylpyrrolidone-vinylacetate copolymer (copovidone) and cellulose derivatives like hydroxy methylcellulose, hydroxy ethylcellulose, hydroxy propylcellulose and hydroxy propylmethylcellulose. Particular preference according to the invention is given to using polyvinyl pyrrolidone. This is commercially available, for example under the name

povidone. The pharmaceutical preparation advantageously comprises from 0 to 10%, preferably from 0.5% to 6%, particularly preferably from 1 to 2% of the wet binder.
According to the present invention the water soluble diluent is selected from polyols such as mannitol, xylitol, sorbitol; polysaccharides such as dextrates, maltodextrin and cyclodextrins. Particular preference according to the invention is given to using mannitol. The pharmaceutical preparation advantageously comprises from 15 to 40%, preferably from 20 to 38%, particularly preferably from 25 to 35% of the water soluble diluent.
According to the present invention the disintegrant is selected from the group consisting of starch, pregelatinized starch, starch glycolates, crosslinked polyvinylpyrrolidone and sodium carboxymethylcellulose (croscarmellose sodium). Particular preference according to the invention is given to using croscarmellose sodium. The pharmaceutical preparation advantageously comprises from 1 to 10%, preferably from 1.5 to 8%, particularly preferably from 2 to 6% of the disintegrant.
According to the present invention the lubricant is selected from the group consisting of from the group consisting of fatty acids and their salts. Particular preference according to the invention is given using magnesium stearate. The pharmaceutical preparation advantageously comprises from 0.2 to 2%, preferably from 0.3 to 1.5%, particularly preferably from 0.4 to 1% of the lubricant.
According to the present invention the glidant is selected from the group consisting of from the group consisting of colloidal silicon dioxide, calcium silicate, magnesium silicate, siUcon hydrogel, talc. Particular preference according to the invention is given using colloidal silicon dioxide. The pharmaceutical preparation advantageously comprises from 0 to 0.5%, preferably from 0.1 to 0.4%, particularly preferably from 0.2 to 0.35% of the glidant. The colors may be selected from any FDA approved colors for internal use. The formulation may optionally be coated.
The dosage form may be in tablet or capsule form, however, the tablet form is particularly suitable. The tablets may ftirther be coated. For coating, any formulation.

which is customary in pharmaceutical technology, such as, for example, those based on hydroxy methyl cellulose and/or polyethylene glycol of various molecular weights may be used.
The pharmaceutical preparation according to the invention is preferably used for the treatment or the prevention of bacterial infections in humans or animals.
The Active Pharmaceutical Ingredient Moxifloxacin and its pharmaceutically acceptable salts or its hydrates prepared by the process disclosed in US 5,849,752 & US 4,990,517 or by the process known in the art.
The invention is further illustrated by the following examples but they should not be construed as limiting the scope of the invention any way. Examples:

Process:
Compound-I and lactose monohydrate were mixed in Shizona mixer to form a partial granulating mixture. This partial granulating mixture was granulated with purified water until coagulate mass obtained. The obtained granules were dried. The dried granules were screened and then the resulting granules were mixed in blender with lactose monohydrate, croscarmellose sodium and colloidal silicon dioxide and magnesium

stearate for 10 minutes. The blend was then subjected to compression on a machine to make tablets.
The cores were coated in a coating pan with hydroxypropyl cellulose and with colouring agents used as titanium dioxide and yellow oxide of iron.

Process;
Compound-I and mannitol were mixed in Shizona mixer to form a partial granulating mixture. Added binder solution of povidone to the above partial granulating mixture and mixed until coagulate mass was obtained. The obtained granules were dried. The dried granules were screened and then the resulting granules were mixed in blender with mannitol, croscarmellose sodium, colloidal silicon dioxide and magnesium stearate for 10 minutes. The blend was then subjected to compression on a machine to make tablets.
The cores were coated in a coating pan with hydroxypropyl cellulose and with colouring agents used as titanium dioxide and yellow oxide of iron.


Process;
Compound-I and lactose monohydrate were mixed in Shizona mixer to form a partial granulating mixture. Added binder solution of povidone to the above partial granulating mixture and mixed until coagulate mass was obtained. The obtained mass was dried. The dried granules were screened and then the resulting granules were mixed in blender with lactose monohydrate, croscarmellose sodium, colloidal silicon dioxide and magnesium stearate for 10 minutes. The blend was then subjected to compression on a machine to make tablets.
The cores were coated in a coating pan with hydroxypropyl cellulose and with colouring agents used as titanium dioxide and yellow oxide of iron.
Dissolution tests with Moxifloxacin Pharmaceutical Tablet Dosage forms:
Dissolution tests of the moxifloxacin pharmaceutical tablet formulation prepared according to the examples 1 to 3 were performed and compared with the dissolution of the reference tablet formulation, i.e., Avelox, marketed by Bayer. These in vitro dissolution tests were conducted using an Apparatus-II (Paddle Method). The comparative dissolution tests were conducted under the following conditions.

Avelox tablets and moxifloxacin tablets of examples 1 to 3 were dissolved in a USP type II apparatus at paddle speed of 50 rpm, at temperature 37° C, in 900 ml of 0.1 N HCl. The results of these dissolution tests are presented in Table-4

Avelox tablets and moxifloxacin tablets of examples 1 to 3 were dissolved in a USP type II apparatus at paddle speed of 50 rpm, at temperature 37° C, in 900 ml of a buffer at pH 6.8. The results of these dissolution tests are presented in Table-5


Avelox tablets and moxifloxacin tablets of examples 1 to 3 were dissolved in a USP type II apparatus at paddle speed of 50 rpm, at temperature 37° C, in 900 ml of a buffer at pH 4.5. The results of these dissolution tests are presented in Table-6

The formulations prepared according to the present invention were in-vitro and in-vivo studies equivalent to the Avelox tablets of Bayer

We claim:
1. A pharmaceutical composition of moxifloxacin, its salts and/or hydrate thereof, which comprises of 26 to 50% of lactose, along with at least one wet binder with a concentration of 0.5 to 10%, at least one disintegrant, at least one lubricant and/ or a glidant.
2. A pharmaceutical composition of moxifloxacin, its salts and/or hydrate thereof, comprising of 26 to 50% of lactose, along with at least one disintegrant, at least one lubricant and/ or a glidant.
3. The pharmaceutical composition of claims 1 and 2, characterized in that the preparation comprises to 30 to 35% of lactose.
4. A pharmaceutical composition of moxifloxacin, its salts and/or hydrate thereof, which consists of water soluble diluent mannitol along with at least one wet binder, at least one disintegrant, at least one lubricant and/ or a glidant.
5. The pharmaceutical composition of claims 1, 3 and 4 characterized in that the wet binder is povidone.
6. The pharmaceutical composition according to preceding claims wherein disintegrant is crascarmellose sodium, lubricant is magnesium stearate, and glidant is colloidal silicon dioxide.
7. A pharmaceutical composition for oral administration of moxifloxacin or a salt and/or hydrate thereof, comprising of lactose, povidone, croscarmellose sodium, magnesium stearate and colloidal silicon dioxide.
8. The pharmaceutical composition for oral administration according claim 1-7, wherein the composition is a tablet, a capsule or granules.

9. Process for the preparation of the pharmaceutical composition according to claims 1
to 8, characterized in the following steps:
a) mixing moxifloxacin, its salts and/or hydrate, with a diluent and a solution of a
binder to obtain homogeneous mixture;
b) drying the obtained granules;
c) mixing of granules with a diluent, a disintegrant, a glidant and a lubricant;
d) compressing the granules obtained in preceding step into tablets;
e) coating of tablets obtained in preceding step.
10. The pharmaceutical composition for oral administration according to claiml-9,
characterized in that the preparation comprises from 50 to 800 mg of moxifloxacin or
its salt and/or hydrates, based on an individual dosage.