FIELD OF INVENTION
The invention relates a Novel crystalline form of Didanosine and pharmaceutical composition thereof, as well as processes for its preparation and manufacture

and its pharmaceutically acceptable salts
BACKGROUND OF THE INVENTION
Didanosine (ddl, dideoxyinosine), a synthetic purine nucleoside analog, is an inhibitor of the in vitro replication of the I Human Immunodeficiency Virus HIV (also known as HTLV III of LAV) in human primary cell cultures and in established cell lines. It is the second antiretroviral agent, after zidovudine, approved by the Food and Drug Administration (FDA) for the treatment of HIV infection.
The chemical name for didanosine is 2',3'-dideoxyinosine and is represented by the
following Formula (I)
o
// ^^T< NH
\ ^^'J ^^ Formula I
Didanosine is a white crystalline powder with the molecular formula C]oHi2N403 and molecular weight of 236.2

PCT application WO 87/01284 to Mitsuya discloses the use.of 2',3'-dideoxyinosine C'ddl") for use against AIDS
US 5,451,671 described purification of crude didanosine by extracting didanosine with a solvent such as an alcohol from a basic solution having a pH of not less than 13 of crude didanosine. Further, the crude didanosine is purified by passing a resin containing column at a pH of not less than 11.
US 6,207,650 disclosed that pure didanosine can be obtained by isolating didanosine as alkali metal or alkaline earth metal salt of didanosine as a crystalline solid and then converting the salt to didanosine.
There are no polymorphs reported in patent literature for didanosine. The present invention deals with novel crystalline didanosine with characteristic XRD pattern
SUMMARY AND OBJECTIVE OF THE INVENTION
It is a principle object of the present invention to provide a novel crystalline form of didaosine
It is another object of the present invention to provide a method for preparing crystalline
Didanosine '
DETAILED DESCKIPTION OF THE INVENTION
Several preferred embodiments of the present invention are described for illustrative purpose, it being understood that the invention may be embodied in other forms not specifically shown in the drawings
Thus in accordance with the present invention, a novel crystalline Didanosine Form I is
provided.

The novel crystalline Didanosine Form I according to the present invention is the compound of following Formula (I)

According to the present invention, the compound of Formula (I) is characterized by an X-ray diffraction pattern as shown in Fig 1, which shows characteristic peaks 29 values at about 6.07 ± 0.2, 9.16 10.60 ± 0.2, 12;20 ± 0.2, 12,59, 13.42 ± 0.2, 15.04 ± 0.2, 15.99 ± 0.2, 17.16 ± 0.2, 17.59 ± 0.2, 18.42 ± 0.2,;18.8 ± 0.2, 19.26± 0.2, 20.33 ± 0.2, 21.35 ± 0.2, 22.03 ± 0.2, 24.88 ± 0.2, 25.80 ± 0.2, 27.12 ± 0.2, 28.69 ± 0.2, 30.32 ± 0.2, 31.55 ± 0.2, 33.69 ± 0.2 35.2 ±0.2, 37.19±0.2, etc
The process for the preparation of Crystalline Didanosine according to the process of the present invention includes the steps of (1) suspending the Didanosine in an alcohol in the presence of base and (2) refluxing the resulting mass and isolating the product.
The base employed is either triethylamine or monomethyl amine.
The process for the preparation of Crystalline Didanosine comprises the steps of (1) dissolving the Didanosine in methanol in the presence of triethylamine and (2) refluxing the resulting mass and isolating the product.
Didanosine is added to methanol at 25-35°C and stirred for 15 minutes. The temperature of the reaction mixture is raised to 55-60°C to get clear solution and the temperature maintained at 55-60°C for 30 minutes. Monomethyl amine is added to the reaction mixture to get a clear solution. The methanol is distilled off under vacuum whereupon a thick residue is obtained

which is subsequently cooled to 5 °C and the solid obtained is filtered and washed with chilled methanol and dried under vacuum to get pure didanosine.
The didanosine of the present invention is prepared by prior-art methods. The didanosine as prepared by the prior-art methods is given in Fig 4
BRIEF DESCRIPTION OF THE DRAWINGS
Fig 1 is X-ray powder difiractogram for the Novel Crystalline Didanosine Form I
Fig 2 is DSC thermogram of the Novel Crystalline Didanosine Form I
Fig 3 is SEM of the Novel Crystalline Form I
Fig 4 is X-Ray poweder diffractogram for prior-art Form H
Examplc-1
Didanosine (24 gms) is added to methanol (1440 ml) at 25-35 °C and stirred for 15 minutes. The temperature of the reaction mixture was raised to 55-60 °C. Monomethyl amine (7.0 ml 25 %w/w) was added to the above mass at 55-60 °C to get clear solution. Activated carbon (1.5 gms) is charged at 55-60 °C and the reaction mass is maintained at 55-60 °C for 30 minutes. The carbon is filtered over celite bed at 55-60 °C and washed with hot methanol (60 ml). Methanol was distilled off under vacuum below 35 °C till the mass volume becomes 150 ml. The reaction mixture was subsequently cooled to 25-35 °C. The obtained thick mass is cooled to 5 °C and maintained at 5-10 °C for 1 hr. The solid obtained is filtered and washed with chilled methanol (2X30 ml) and dried under vacuum to give 30 gms of didanosine Form I
ExampIe-2

Didanosine (3 gm) is added to Methanol (180 ml) at 25-35°C and stir for 15 mins. Slowly temperature was raised: to 55-60°C. Triethylamine (0.9 gm) was added to the above mass at 55-60°C to get clear solution. Activated carbon (0.25 gm) was charged at 55-60°C. The reaction mass was maintained at 55-60°C for 30 mins. The carbon is filtered over celite bed at 55-6G°C and washed with hot Methanol (5 ml). Distilled off methanol under vacuum below 35°C up to the residual volume of 15 ml, Thick mass is cooled to 5°C and maintained at 5-10°C for 1 hr. Solid is filtered and washed with chilled Methanol ( 5 ml), dried under vacuum below 35°C to give 2.4 gm of Didanosine Form I

WE CLAIM :
1. Crystalline Form I ofDidanosine
2. Crystalline Form I ofDidanosine having the characteristic X-ray diffraction peaks at
2-thela values of about 6.07 ±0.2, 9.16 10.60 ± 0.2, 12.20 ± 0.2, 12,59, 13.42 ±0.2,
15.04 ± 0.2, 15.99 ± 0.2, 17.16 ± 0.2, 17.59 ± 0.2, 18.42 ± 0.2, 18.8 ± 0.2, 19.26±
0.2, 20.33 ± 0.2, 21.35 ± 0.2, 22.03 ± 0.2, 24.88 ± 0.2, 25.80 ± 0.2, 27.12 ± 0.2, 28.69
± 0.2, 30.32 ± 0.2, 31.55 ± 0.2, 33.69 ± 0.2 35.2 ± 0.2, 37.19± 0.2.
2. The crystalline Didanosine according to claim 1 characterized by a differential scanning calorimetry thermogram having a peak at about 185 °C
3. A process for the preparation of Crystalline Form I of Didanosine of claim 1, which comprises the steps of
i) Suspending didanosine in methanol in presence of base
ii) refluxing the resulting mass iii) Isolating the product