FIELD OF THE INVENTION:

The present invention relates to a novel polymorphic form of Catechin hydrate, process for preparation of said polymorphic form and pharmaceutical composition comprising the same.

BACKGROUND OF THE INVENTION:

For 3,000 years, before tea became a social and recreational beverage, tea was used as a medicine and wisely so it would seem. The tea plant, Camellia sinensis, is proving to be a powerhouse with an array of cancer fighting phytochemicals (non-nutrient plant chemicals). The most promising of these is catechin, a tannin derivative that gives tea its astringency and is commonly available from many plants such as grapes, berries, and ferns.

Catechin (2R, 3iS)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-2//-chromene-3,5,7-triol, is poorly soluble naturally occurring polyphenol found in the leaves of both green and black teas. Green teas have much higher levels of Catechin than do black teas. Catechin has a wide range of biological activity and is implicated in modulating a number of inflammatory pathways. Catechins defeat cancer in at least one of three ways. First, they can prevent the formation of carcinogens, second, they turn up the body's natural detoxification defenses, and finally, they suppress cancer promotion.

Green tea catechins have also been shown to possess antibiotic properties due to their role in disrupting a specific stage of the bacterial DNA replication process. Further, it helps in regulating cholesterol and blood pressure; reducing blood clotting tendencies that may cause heart attacks or strokes. Epidemiological studies suggest that those populations that drink more green tea live longer than those that don't.

IE830383 relates to Catechin in anhydrous and monohydrate crystal forms.

INI57218 (US4515804) relates to (+)-catechin alpha monohydrate and process for the
same.

JP 59231081 relates to novel crystal (+) catechin monohydride and anhydrous (+) catechin.

However, the stability and solubility of the above forms are not reported. Moreover, the above prior art fails to provide polymorphic form of catechin hydrate having high solubility thereby increasing its bioavailability. Also, the commercially available (+)-Catechin crystal forms have serious disadvantages during the manufacturing of the pharmaceutical preparations due to the change in the degree of hydration at ordinary temperatures. Hence, the (+)-catechin content in pharmaceutical preparations which has to be accurate, is not achieved.

Thus, it is an object of the current inventors to provide a new polymorphic form of Catechin hydrate which is more soluble and stable than the known or commercially available Catechin hydrates thereby increasing its bioavailability. It was also an interest to find a suitable solvent where the crystallization can be performed at a temperature near to ambient temperature, for solving the inconsistency/operational problems in the prior art, yielding polymorph of catechin hydrate in more soluble form. Further, interest was to see its workability at higher temperature to affect a fast and easily dispersible crystallization conditions, an important factor for operations.

SUMMARY OF THE INVENTION:

In accordance to the above objective, the present invention provides a novel polymorphic form of Catechin hydrate having more solubility which is characterized by PXRD, DSC, IR spectroscopy.

It is another aspect of the present invention to provide novel polymorphic form of Catechin hydrate characterized as having an x-ray powder diffraction peaks at 2.theta = 7.70, 16.40, 19.14, 23.40, 25.74, 40.74.

It is yet another aspect of the present invention to provide industrially reliable process for preparation of stable Catechin hydrate polymorph without contamination of other forms; comprising of sonicating catechin hydrate in polar solvents selected from ketones, alcohols, alkanoic acids, esters and the like, followed by slow evaporation till the crystals
observed.

In yet another aspect, the present invention is to provide a pharmaceutical composition
containing Catechin hydrate polymorph as active ingredient with one or more
pharmaceutically acceptable carriers/ exicipients.

DESCRIPTION OF DRAWINGS:

Fig 1 shows the IR profile of Catechin hydrate
Fig 2 shows the IR profile of Catechin hydrate polymorph
Fig 3 shows PXRD profile of Catechin hydrate
Fig 4 shows PXRD profile of Catechin hydrate polymorph
Fig 5 shows DSC of Catechin hydrate
Fig 6 shows DSC of Catechin hydrate polymorph
Fig 7 shows Dissolution Profile of Catechin hydrate and Catechin hydrate polymorph.

DETAILED DESCRIPTION OF THE INVENTION:

The invention will now be described in detail in connection with certain preferred and
optional embodiments; so that various aspects thereof may be more fully understood and
appreciated.

According to the preferred embodiment the present invention provides novel polymorphic form of Catechin hydrate having more thermal stability, solubility and which is haracterized by PXRD, DSC, and IR spectroscopy.

The solubility of naturally occurring (commercially available) Catechin hydrate in water is poor whereas the novel polymorphic form of the current invention is observed to have 12% or upto 25% more solubility than the known form of Catechin hydrate.
Accordingly the present invention in one of the embodiment provides the dissolution profile of Catechin hydrate vis-a-vis Catechin hydrate polymorph of the current invention as tabulated below:

Further, the comparison of physical characteristics of novel Catechin hydrate polymorph and commercially available Catechin hydrate is tabulated below:

Another embodiment of the present invention provides process for preparation of stable Catechin hydrate polymorph, comprising following steps;

a. sonicating Catechin hydrate in polar solvents selected from ketones, alcohols,
alkanoic acids, esters and the like, and

b. slowly evaporating the mixture of step (a) till crystals of Catechin hydrate
polymorph are obtained.

In yet another embodiment the present invention provides pharmaceutical composition containing catechin hydrate polymorph as active ingredient with one or more pharmaceutical^ acceptable carriers/ excipients.

The pharmaceutical composition may be a solid form, a liquid suspension or an injectable composition. The active ingredient and excipients can be formulated into compositions and dosage forms according to methods known in the art. The oral administration may be accomplished by ingesting the composition preferably in a form of tablet/capsule/liquid with a glass of water. The other dosage forms like hard gelatin capsules, powders, liquid capsules, syrups, suspensions, elixirs are also equally good modes of oral administration.

It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative examples and that the present invention may be embodied in other specific forms without departing from the essential attributes thereof, and it is therefore desired that the present embodiments and examples be considered in all respects as illustrative and not restrictive, reference being made to the appended claims, rather than to the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.

EXAMPLES:

Example 1: Preparation of Catechin hydrate polymorph 20mg of commercially available catechin hydrate (Sigma-Aldrich) + 5 ml acetone -sonicated for 1 hr, followed by slow evaporation - yields the new polymorph of catechin hydrate.

Dissolution of polymorph of catechin hydrate:

Catechin hydrate polymorph was taken in 50 ml round bottom flask and 50 ml of nano pure water added over it. This solution was stirred at 300 rpm. 5 ml of solution was taken out at 5, 10, 30, 60 and 120 minutes interval and filtered through Whatman 40 filter paper. The filtrate was diluted by 10 times and UV absorption was measured. The absorbance was plotted in origin to get dissolution profile curve, (refer Fig 7)

We claim,

1. A highly soluble, thermally stable polymorphic form of Catechin hydrate characterized as having an x-ray powder diffraction peaks at 2.theta = 7.70, 16.40, 19.14, 23.40, 25.74, 40.74.

2. The highly soluble, thermally stable polymorphic form of Catechin hydrate according to claim 1, further characterized as having an x-ray powder diffraction pattern substantially identical to FIG. 4.

3. The highly soluble, thermally stable polymorphic form of Catechin hydrate according to claim 1, characterized as having an infrared spectrum at 3247 cm"1, 2050 cm-1, 1626 cm'1, 1289 cm"1, 1148 cm"1, 823 cm"1.

4. The highly soluble, thermally stable polymorphic form of Catechin hydrate as claimed in claim 3, further characterized as having an infrared spectrum substantially identical to FIG. 2.

5. The highly soluble, thermally stable and highly soluble polymorphic form of Catechin hydrate according to claim 1, characterized as having DSC substantially identical to FIG. 6.

6. A process to prepare polymorphic form of Catechin hydrate according to claim 1, comprising following steps:

a. sonicating Catechin hydrate in polar solvents selected from ketones,
alcohols, alkanoic acids, esters and the like, and

b. slowly evaporating the mixture of step (a) till crystals of Catechin hydrate
polymorph are obtained.

7. A pharmaceutical composition comprising polymorphic form of Catechin hydrate according to claim 1, together with pharmaceutically acceptable carriers and excipients.

8. The pharmaceutical composition according to claim 7, wherein said composition is in solid form, a liquid suspension or an injectable form.