FIELD OF THE INVENTION

The present invention provides acid addition salts of Rilpivirine and processes for preparation of the same.

BACKGROUND OF THE INVENTION

Retroviruses are class of viruses which lower the immunity levels in mammals particularly Humans. Human Immuno deficiency Virus is one such retrovirus which causes AIDS. Short life cycle and high error rate causes the virus to mutate very rapidly, resulting in a high genetic variability of HIV. Antiretruviral drugs include Nucleoside reverse transcriptase inhibitors (NRTPs), Non- Nucleoside reverse transcriptase inhibitors (NNRTI's), HIV protease inhibitors, fusion inhibitors, maturation inhibitors. Compound 4-((4-((4-((lE)-2-Cyanoethenyl)-2,6- dimethyIphenyl)amino)-2-pyrimidinyl) amino)benzo- nitriie [TMC278], generically designated as Rilpivirine is shown below.

Rilpivirine is an investigational new drug developed by Tibotec a biotechnology company in Belgium, for the treatment of HIV infection. It is a second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs). Rilpivirine prevents HIV from entering the nucleus of healthy CD4 cells. This prevents the cells from producing new virus and decreases the amount of virus in the body. Rilpivirine is being studied in combination with other HIV medicines in two groups of HIV-positive people: those starting HIV treatment for the first time and those in need of newer medicines to treatment HIV that has become resistant to older options.

US 7,125,879 specifically claims Rilpivirine. This patent discloses various processes for the preparation of Rilpivirine one of which involves condensation of 3-(4-amino-3,5-dimethylphenyl)-acrylonitrile either in free base or hydrochloride salt with 4-{4* chloropyrimidin-2-ylaniino)benzonitrile using potassium carbonate.

US 2006/0111379 Al discloses Rilpivirine hydrochloride salt and its polymorphic form is designated as Form A. This patent application also discloses solvates or pseudo polymorphic forms of Rilpivirine hydrochloride Form B, Form C and Form D respectively.

WO 2009/007441 designates crystalline Rilpivirine of US 7,125,879 as Polymorphic Form II. Rilpivirine polymorphic form II is characterized by PXRD peaks at about 8.5, 12.4, 12.9,17.6, 21.0,24.8, 25.8 and 27.9 ±0.2 9° and DSC thermogram showing melting at 243.2°C. This patent application claims another polymorphic form of Rilpivirine designated as Polymorphic Form I. The given morph is characterized by PXRD peaks at about 9.0, 11.3, 14.3, 17.1, 19.2, 24.2 and 27.6 ± 0.2 6° and DSC thermogram showing melting at 257.5°C. The polymorphs also differ in their IR spectrum with typical absorption bands at about 3348, 3274, 2217, 2209, 1477 and 1334 cm-1

OBJECT OF THE INVENTION

Principle object of the present invention is to provide Rilpivirine Malonate and process for the preparation of the same.

Another principle object of the present invention is to provide Rilpivirine Succinate and process for the preparation of the same.

Yet another principle object of the present invention is to provide Rilpivirine Adipate and process for the preparation of the same.

Still another principle object of the present invention is to provide Rilpivirine Fumarate and process for the preparation of the same.

Another principle object of the present invention is to provide Rilpivirine Malate and process for the preparation of the same.

Another principle object of the present invention is to provide Rilpivirine Maleate and process for the preparation of the same.

Another principle object of the present invention is to provide Rilpivirine Tartarate and process for the preparation of the same.

Another principle object of the present invention is to provide Rilpivirine Saccharinate and process for the preparation of the same.

SUMMARY OF THE INVENTION

Main aspect of the present invention is to provide novel organic acid addition salts of 4-((4-((4-((lE)-2-Cyanoethenyl)-2,6-dimethylphenyl)amino)-2-pyrimidinyl)amino) benzonitrile [Rilpivirine]. The salts include Malonate, Succinate, Adipate, Fumarate, Malate, Maleate, Tartarate and Saccharinate. The present invention also aims to provide processes for the preparation of the said sahs of Rilpivirine.

In one aspect, the present invention provides novel salt Rilpivirine Malonate.

The present invention also provides process for the preparation of Rilpivirine Malonate comprising the steps of: a) adding Rilpivirine and malonic acid in a solvent or mixtures thereof; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Malonate.

In another aspect, the present invention provides novel salt Rilpivirine Succinate.

The present invention also provides process for the preparation of Rilpivirine Succinate the steps of: a) adding Rilpivirine and succinic acid in a solvent or mixtures thereof; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Succinate.

In another aspect, the present invention provides novel salt Rilpivirine Adipate.

The present invention also provides process for the preparation of Rilpivirine Adipate comprising the steps of: a) adding Rilpivirine and adipic acid in a solvent or mixtures thereof; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Adipate.

In another aspect, the present invention provides novel salt Rilpivirine Fumarate.

The present invention also provides process for the preparation of Rilpivirine Fumarate comprising the steps of: a) adding Rilpivirine and fumaric acid in a solvent or mixtures thereof; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Fumarate.

In another aspect, the present invention provides novel sah Rilpivirine Malate.

The present invention also provides process for the preparation of Rilpivirine Malate comprising the steps of: a) adding Rilpivirine and malic acid in a solvent or mixtures thereof; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Malate.

In another aspect, the present invention provides novel salt Rilpivirine Maleate.

The present invention also provides process for the preparation of Rilpivirine Maleate comprising the steps of: a) adding Rilpivirine and maleic acid in a solvent; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Maleate.

In one embodiment, the present invention provides novel salt Rilpivirine Malonate.

Accordingly, the present invention provides crystalline Rilpivirine Malonate characterized by Powder X-ray diffraction pattern as shown in figure 1, comprising peaks at about 6.25, 9.20, 11.87, 15.14, 15.48, 18.39, 22.09, 22.92, 23.30, 24.63, 27.17, 27.74, 28.46 ±0.26°.

According to the present invention, crystalline Rilpivirine Malonate is further characterized by Powder X-ray diffraction pattern comprising peaks at about 6.25, 9.20, 11.09, 11.87, 12.46, 15.14, 15.48, 18.39, 19.41, 21.19, 22.09, 22,92, 23.30, 24.63, 27.17, 27.74, 28.46 ± 0.2 θ ˚.

The present invention also provides process for the preparation of Rilpivirine Malonate comprising the steps of: a) adding Rilpivirine and malonic acid in a solvent or mixtures thereof; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Malonate.

According to the present invention, Rilpivirine is suspended with malonic acid in a solvent at ambient temperature. The solvent group is selected from alcohols and chlorinated solvents, methanol, ethanol, propanol, n-butanol, methylene dichloride, chloroform and tetrachloroethane or mixtures thereof preferably methanol and chloroform mixture. The suspension is heated to 50-80°C preferably 60-70°C to clear the contents. The clear solution so obtained is cooled to room temperature (25-30°C). The cooled mass is added slowly to anti-solvent selected from alkanes, ethers such as n-hexane, n-heptane, isopropyl ether [IPE], diethyl ether, preferably isopropyl ether. The solid obtained is filtered, washed with isopropyl ether and dried under reduced pressure to get Rilpivirine Malonate.

In another embodiment, the present invention provides novel salt Rilpivirine Succinate.

In another aspect, the present invention provides novel salt Rilpivirine Tartarate.

The present invention also provides process for the preparation of Rilpivirine Tartarate comprising the steps of; a) adding Rilpivirine and tartaric acid in a solvent or mixtures thereof; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Tartarate.

In another aspect, the present invention provides novel salt Rilpivirine Saccharinate.

The present invention also provides process for the preparation of Rilpivirine Saccharinate comprising the steps of: a) adding Rilpivirine and saccharin in a solvent or mixtures thereof; h) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Saccharinate.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 relates to PXRD of Crystalline Rilpivirine Malonate.

Figure 2 relates to PXRD of Crystalline Rilpivirine Succinate.

Figure 3 relates to PXRD of Crystalline Rilpivirine Adipate.

Figure 4 relates to PXRD of Crystalline Rilpivirine Fumarate.

Figure 5 relates to PXRD of Crystalline Rilpivirine Malate.

Figure 6 relates to PXRD of Crystalline Rilpivirine Maleate.

Figure 7 relates to PXRD of Crystalline Rilpivirine Tartarate.

Figure 8 relates to PXRD of Crystalline Rilpivirine Saccharinate,

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to novel organic acid addition salts of 4-((4-((4-((lE)-2-Cyanoethenyl)-2,6-dimelhylphenyl)amino)-2-pyrimidinyl)amino)benzonitrle [Rilpivirine], The salts include Malonate, Succinate, Adipate, Fumarate, Malate, Maleate, Tartarate and Saccharinate. The present invention also relates to processes for the preparation of the said salts of Rilpivirine. The present invention also relates to highly pure Rilpivirine and its pharmaceutical acceptable salts.

Accordingly, the present invention provides crystalline Rilpivirine Succinate characterized by Powder X-ray diffraction pattern as shown in figure 2, comprising peaks at about 6.38, 14.31,19.09, 20.10, 20.36, 22.84, 26.10, ± 0.2 θ ˚ .

According to the present invention, crystalline Rilpivirine Succinate is further characterized by Powder X-ray diffraction pattern comprising peaks at about 6.38, 14.31, 14.62, 14.94, 19.09, 20.10, 20.36, 22.42, 22.84, 23,48, 25.29, 26.10, 28,44 ± 0.2 θ ˚.

The present invention also provides process for the preparation of Rilpivirine Succinate comprising the steps of: a) adding Rilpivirine and succinic acid in a solvent or mixtures thereof; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Succinate.

According to the present invention, Rilpivirine is suspended with succinic acid in a solvent at ambient temperature. The solvent group is selected from alcohols and chlorinated solvents, methanol ethanol, propanol, n-butanol, methylene dichloride, chloroform and tetrachloroethane or mixtures thereof preferably methanol and chloroform mixture. The suspension is heated to 50-80°C preferably 60-70°C to clear the contents. The clear solution so obtained is cooled to room temperature (25-30 ˚C). The cooled mass is added slowly to anti-solvent selected from alkanes, ethers such as n-hexane, n-heptane, isopropyl ether [IPE], diethyl ether, preferably isopropyl ether. The solid obtained is filtered, washed with isopropyl ether and dried under reduced pressure to get Rilpivirine Succinate.

In another embodiment, the present invention provides novel salt Rilpivirine Adipate.

Accordingly, the present invention provides crystalline Rilpivirine Adipate characterized by Powder X-ray diffraction pattern as shown in figure 3, comprising peaks at about 5.20, 5.68, 8,45, 9.64, 9.96, 12.84, 13.13, 14.95, 15.74, 17.60, 18.17, 18.58, 19.30, 19.64,20.12,21.81, 22.62,23.01, 23.45, 25.76,27.44 ± 0.2 θ ˚.

According to the present invention, crystalline Rilpivinne Adipate is further characterized by Powder X-ray diffraction pattern comprising peaks at about 5,20, 5.68, 8.45, 9.64, 9.96, 12,84, 13.13, 14.47, 14.95, 15.74, 16.38, 16.91, 17.60, 18.17, 18.58, 19.30, 19.64, 20.12, 21.81, 22.62, 23.01, 23.45, 23,89, 25.76, 27.44, 28.68 ± 0.2 θ ˚.

The present invention also provides process for the preparation of Rilpivirine Adipate comprising the steps of: a) adding Rilpivirine and adipic acid in a solvent or mixtures thereof; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Adipate.

According to the present invention, Rilpivirine is suspended with adipic acid in a solvent at ambient temperature. The solvent group is selected from alcohols and chlorinated solvents, methanol, ethanol, propanolf n-butanol, methylene dichloride, chloroform and tetrachloroethane or mixtures thereof preferably methanol and chloroform mixture. The suspension is heated to 50-80°C preferably 60-70°C to clear the contents. The clear solution so obtained is cooled to room temperature (25-30°C), The cooled mass is added slowly to anti-solvent selected from alkanes, ethers such as n-hexane, n-heptane, isopropyl ether [IPE], diethyl ether, preferably isopropyl ether. The solid obtained is filtered, washed with isopropyl ether and dried under reduced pressure to get Rilpivirine Adipate.

In another embodiment, the present invention provides novel salt Rilpivirine Fumarate.

Accordingly, the present invention provides crystalline Rilpivirine Fumarate characterized by Powder X-ray diffraction pattern as shown in figure 4, comprising peaks at about 5,42, 9.32, 14.23, 15.19, 18.02, 18.78, 19.45, 23.17, 23.59, 23.99, 26.79, 27.99 ±0.2 θ ˚.

According to the present invention, crystalline Rilpivirine Fumarate is further characterized by Powder X-ray diffraction pattern comprising peaks at about 5,42, 9.32, 10.76, 14.23, 15.19, 16.02, 18.02, 18.78, 19.45, 21.60, 22.73, 23.17, 23.59, 23.99, 24.71, 26.79, 27.99 ± 0.2 θ ˚.

The present invention also provides process for the preparation of Rilpivirine Fumarate comprising the steps of: a) adding Rilpivirine and fumaric acid in a solvent or mixtures thereof; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Fumarate.

According to the present invention, Rilpivirine is suspended with fumaric acid in a solvent at ambient temperature. The solvent group is selected from alcohols and chlorinated solvents, methanol, ethanol, propanol, n-butanol, methylene dichloride, chloroform and tetrachloroethane or mixtures thereof preferably methanol and chloroform mixture. The suspension is heated to 50-80°C preferably 60-70°C to clear the contents. The clear solution so obtained is cooled to room temperature (25-30°C). The cooled mass is added slowly to anti-solvent selected from alkanes, ethers such as n-hexane, n-heptane, isopropyl ether [IPE], diethyl ether, preferably isopropyl ether. The solid obtained is filtered, washed with isopropyl ether and dried under reduced pressure to get Rilpivirine Fumarate.

In yet another embodiment, the present invention provides novel salt Rilpivirine Malate.

Accordingly, the present invention provides crystalline Rilpivirine Malate characterized by Powder X-ray diffraction pattern as shown in figure 5, comprising peaks at about 5.52, 9.69, 12.41, 14.79, 18.31, 19,63 ±0.2 θ ˚.

According to the present invention, crystalline Rilpivirine Malate is further characterized by Powder X-ray diffraction pattern comprising peaks at about 5.52, 9.23, 9.69,12.41,14.79, 15.77, 17.30, 18.31,19.63 ± 0.2 θ ˚.

The present invention also provides process for the preparation of Rilpivirine Malate comprismg the steps of: a) adding Rilpivirine and malic acid in a solvent or mixtures thereof; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Malate.

According to the present invention, Rilpivirine is suspended with malic acid in a solvent at ambient temperature. The solvent group is selected from alcohols and chlorinated solvents, methanol, ethanol, propanol, n-butanol, methylene dichloride, chloroform and tetrachloroethane or mixtures thereof preferably methanol and chloroform mixture. The suspension is heated to 50-80°C preferably 60-70°C to clear the contents. The clear solution so obtained is cooled to room temperature (25-30 ˚C). The cooled mass is added slowly to anti-solvent selected ft'om alkanes, ethers such as n-hexane, n-heptane, isopropyl ether [IPE], diethyl ether, preferably isopropyl ether. The solid obtained is filtered, washed with isopropyl ether and dried under reduced pressure to get Rilpivirine Malate.

In yet another embodiment, the present invention provides novel salt Rilpivirine Maleate.

Accordingly, the present invention provides crystalline Rilpivirine Maleate characterized by Powder X-ray diffraction pattern as shown in figure 6, comprising peaks at about 10.63, 13.37, 14,99, 15.23, 16.99, 18.39, 19.71, 21.05, 22.59, 22.92, 23.24, 25.18 ±0.2e According to the present invention, crystalline Rilpivirine Maleate is further characterized by Powder X-ray diffraction pattern comprising peaks at about 10.63, 13.37, 14.99, 15.23, 16.99, I8J9, 18.67, 19.01, 19.71, 20.53, 21.05, 21.82, 22.59, 22.92, 23.24, 25.18, 28.11, 29.42, 34.32 ± 0.2 θ ˚.

The present invention also provides process for the preparation of Rilpivirine Maleate comprising the steps of; a) adding Rilpivirine and maleic acid in a solvent; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Maleate.

According to the present invention, Rilpivirine is suspended with maleic acid in a solvent at ambient temperature. The solvent group is selected from alcohols and chlorinated solvents, methanol, ethanol, propanol, n-butanol, methylene dichloride, chloroform and tetrachloroethane or mixtures thereof preferably methanol and chloroform mixture. The suspension is heated to 50-80''C preferably 60-70°C to clear the contents. The clear solution so obtained is cooled to room temperature (25-30C). The cooled mass is added slowly to anti-solvent selected from alkanes, ethers such as n-hexane, n-heptane, isopropyl ether [IPE], diethyl ether, preferably isopropyl ether. The solid obtained is filtered, washed with isopropyl ether and dried under reduced pressure to get Rilpivirine Maleate.

In yet another embodiment the present invention provides novel salt Rilpivirine Tartarate.

Accordingly, the present invention provides crystalline Rilpivirine Tartarate characterized by Powder X-ray diffraction pattern as shown in figure 7, comprising peaks at about 5.19, 5.57, 9.85, 12.26, 15.01, 17.32, 17.92, 18.58, 19.70, 25.86 ± 0.29.

According to the present invention, crystalline Rilpivirine Tartarate is further characterized by Powder X-ray diffraction pattern comprising peaks at about 5.19, 5.57, 9.20, 9.85, 12.26, 14.31, 15.01, 15.65, 17.32, 17,92, 18.58, 18.84, 19.70, 21,70, 22.13,22.52,23.85, 25.86, 27.27 ± 0.2 θ ˚.

The present invention also provides process for the preparation of Rilpivirine Tartarate comprising the steps of: a) adding Rilpivirine and tartaric acid in a solvent or mixtures thereof; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Tartarate.

According to the present invention, Rilpivirine is suspended with tartaric acid in a solvent at ambient temperature. The solvent group is selected from alcohols and chlorinated solvents, methanol, ethanol, propanol, n-butanol methylene dichloride, chloroform and tetrachloroethane or mixtures thereof preferably methanol and chloroform mixture. The suspension is heated to 50-80°C preferably 60-70°C to clear the contents. The clear solution so obtained is cooled to room temperature (25-30°C).

The cooled mass is added slowly to anti-solvent selected from alkanes, ethers such as n-hexane, n-heptane, isopropyl ether [IPE], diethyl ether, preferably isopropyl ether. The solid obtained is filtered, washed with isopropyl ether and dried under reduced pressure to get Rilpivirine Tartarate.

In yet another embodiment, the present invention provides novel salt Rilpivirine Saccharinate.

Accordingly, the present invention provides crystalline Rilpivirine Saccharinate, characterized by Powder X-ray diffraction pattern as shown in figure 8, comprising peaks at about 12.43, 12.80, 15.90, 16.74, 17.53, 19.09, 22.87, 23.72, 24.14, 24.97, ± 0.29°.

According to the present invention, clystalline Rilpivirine Saccharinate is further characterized by Powder X-ray diffraction pattern comprising peaks at about 7.99, 12.43, 12.80, 15.90, 16.74, 17.53, 19.09, 20.06, 20.78, 22.39, 22.87, 23.72, 24.14, 24.97, 25.68, 29.26 ±0.29.

The present invention also provides process for the preparation of Rilpivirine Saccharinate comprising the steps of: a) adding Rilpivirine and saccharin in a solvent or mixtures thereof; b) heating the suspension to obtain clear solution; c) cooling the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine Saccharinate.

According to the present invention, Rilpivirine is suspended with saccharin in a solvent at ambient temperature. The solvent group is selected from alcohols and chlorinated solvents, methanol, ethanol, propanol, n-butanol, methylene dichloride, chloroform and tetrachloroethane or mixtures thereof preferably methanol and chloroform mixture. The suspension is heated to 50-80°C preferably 60-70°C to clear the contents. The clear solution so obtained is cooled to room temperature (25-30°C). The cooled mass is added slowly to anti-solvent selected from alkanes, ethers such as n-hexane, n-heptane, isopropyl ether [IPE], diethyl ether, preferably isopropyl ether. The solid obtained is filtered, washed with isopropyl ether and dried under reduced pressure to get Rilpivirine Saccharinate.

In one more aspect, the present invention relates a pharmaceutical composition that includes a therapeutically effective amount of Rilpivirine organic acid addition salt and one or more pharmaceutically acceptable carriers, excipients or diluents.

Accordingly, the pharmaceutical composition comprising Rilpivirine organic acid addition salt along with one or more pharmaceutically acceptable carriers of this invention may further be formulated as: solid oral dosage forms such as, but not limited to, powders, granules, pellets, tablets, and capsules; liquid oral dosage forms such as but not limited to syrups, suspensions, dispersions, and emulsions, and injectable preparations such as but not limited to solutions, dispersions, and freeze dried compositions. Formulations may be in the form of immediate release, delayed release or modified release. The compositions may be prepared by direct blending, dry granulation, or wet granulation or by extrusion and spheronization. Compositions may be presented as uncoated, film coated, sugar coated, powder coated, enteric coated or modified release coated. Compositions of the present invention may further comprise one or more pharmaceutically acceptable excipients.

INSTRUMENTATION

Powder X-ray Diffraction (PXRD)

The said crystalline salts of the present invention are characterized by their X-ray powder diffraction pattern. Thus, the X-ray diffraction patterns of said crystalline salts of the invention were measured on PANalytical, X'Pert PRO powder diffractometer equipped with goniometer of θ / θ configuration and X'Celerator detector. The Cu-anode X-ray tube was operated at 40kV and 30mA. The experiments were conducted over the 20 range of 2.0°-50.0°, 0.030° step size and 50 seconds step time.

The following examples illustrate the invention but do not limit the scope of the invention in any way.

Example 1

Preparation of Rilpivirine Malonate

Rilpivirine (1 gm) and malonic acid (0.284 g) were suspended in 1:1 mixture of methanol and chloroform (60 ml). The contents were heated to 60-70 ˚C to form a clear solution. The resulting clear solution was cooled to 25-30°C and slowly added to IPE (100 ml) and stirred for 1 hour at room temperature. The solid obtained was filtered, washed with IPE (10 ml) and suck dried for 15 min under vacuum at 25-30°C. The solid obtained was identified as a crystalline Rilpivirine Malonate.

Example 2

Preparation of Rilpivirute Succinate

Rilpivirine (1 gm) and succinic acid (0.322 g) suspended in 1:1 mixture of methanol and chloroform (60 ml). The contents were heated to 60-70 ˚C to form a clear solution. The resulting clear solution was cooled to 25-30°C and slowly added to IPE (100 ml) and stirred for 1 hour at room temperature. The solid obtained was filtered, washed with IPE (10 ml) and suck dried for 15 min under vacuum at 25-30 ˚C. The solid obtained was identified as a crystalline Rilpivirine Succinate.

Example 3

Preparation of Rilpivirine Adipate

Rilpivirine (1 gm) and adipic acid (0.40 g) were suspended in 1:1 mixture of methanol and chloroform (60 ml). The contents were heated to 60-70°C to form a clear solution. The resulting clear solution was cooled to 25-30*'C and slowly added to IPE (100 ml) and stirred for 1 hour at room temperature. The solid obtained w^ filtered, washed with IPE (10 ml) and suck dried for 15 min under vacuum at 25-30°C. The solid obtained was identified as a crystalline Rilpivirine Adipate.

Example 4

Preparation of Rilpivirine Fumarate

Rilpivirine (1 gm) and fumaric acid (0.316 g) were suspended in 1:1 mixture of methanol and chloroform (60 ml). The contents were heated to 60-70°C to form a clear solution. The resulting clear solution was cooled to 25-30°C and slowly added to IPE (100 ml) and stirred for 1 hour at room temperature. The solid obtained was filtered, washed with IPE (10 ml) and suck dried for 15 min under vacuum at 25-30°c. The solid obtained was identified as a crystalline Rilpivirine Fumarate.

Example 5

Preparation of Rilpivirine Malate

Rilpivirine (1 gm) and malic acid (0.366 g) were suspended in 1:1 mixture of methanol and chloroform (60 ml). The contents were heated to 60-70°C to form a clear solution. The resuhing clear solution was cooled to 25-30°C and slowly added to IPE (100 ml) and stirred for 1 hour at room temperature. The solid obtained was filtered, washed with IPE (10 ml) and suck dried for 15 min under vacuum at 25-30°C. The solid obtained was identified as a crystalline Rilpivirine Malate.

Example 6

Preparation of Rilpivirine Maleate

Rilpivirine (1 gm) and maleic acid (0.316 g) were suspended in 1:1 mixture of methanol and chloroform (60 ml). The contents were heated to 60-70°C to form a clear solution. The resuhing clear solution was cooled to 25-30°C and slowly added to IPE (100 ml) and stirred for 1 hour at room temperature. The solid obtained was filtered, washed with IPE (10 ml) and suck dried for 15 min under vacuum at 25-30°C. The solid obtained was identified as a crystalline Rilpivirine Maleate.

Example 7

Preparation of Rilpivirine Tartarate

Rilpivirine (1 gm) and tartaric acid (0.409 g) were suspended in 1:1 mixture of methanol and chloroform (60 ml). The contents were heated to 60-70'^C to form a clear solution. The resulting clear solution was cooled to 25-30*'C and slowly added to IPE (100 ml) and stirred for 1 hour at room temperature. The solid obtained was filtered, washed with IPE (10 ml) and suck dried for 15 min under vacuum at 25-30°C. The solid obtained was identified as a crystallme Rilpivirine Tartarate.

Example 8

Preparation of Rilpivirine Saccharinate

Rilpivirine (1 gm) and saccharin (0.50 g) were suspended in 1:1 mixture of methanol and chloroform (60 ml). The contents were heated to 60-70°C to form a clear solution. The resuhing clear solution was cooled to 25-30°C and slowly added to IPE (100 ml) and stirred for 1 hour at room temperature. The solid obtained was filtered, washed with IPE (10 ml) and suck dried for 15 min under vacuum at 25-30'*C. The solid obtained was identified as a crystalline Rilpivirine Saccharinate.

Claim,

1. A process for the preparation of Rilpivirine organic acid addition salt, comprising the steps of: a) adding Rilpivirine and organic acid in a solvent or mixtures thereof; b) heating the suspension to obtain clear solution; c) cooing the clear solution and adding this clear solution to anti-solvent; and d) isolating Rilpivirine organic acid addition salt; wherein organic acid addition salt is selected from Malonate, Succinate, Adipate, Fumarate, Malate, Maleate, Tartarate or Saccharinate.

2. The crystalline Rilpivirine Malonate obtained according to claim 1, wherein the Rilpivirine Malonate is characterized by powder X-ray diffractogram having peaks at about 6.25, 9.20, 11.87, 15.14, 15.48, 18.39, 22.09, 22.92, 23.30, 24.63, 27.17, 27.74, 28.46 ±0.2 θ ˚.

3. The crystalline Rilpivirine Succinate obtained according to claim 1, wherein the Rilpivirine Succinate is characterized by powder X-ray diffractogram having peaks at about 6.38, 14.31, 19.09, 20.10,20.36, 22.84,26.10, ± 0.2 θ ˚.

4. The crystalline Rilpivirine Adipate obtained according to claim 1, wherein the Rilpivirine Adipate is characterized by powder X-ray diffractogram having peaks at about 5.20, 5.68, 8,45, 9.64, 9.96, 12.84, 13.13, 14.95, 15.74, 17.60, 18.17, 18.58, 19.30,19.64, 20.12, 21.81, 22.62, 23.01, 23.45, 25.76, 27,44 ± 0.2 θ ˚.

5. The crystalline Rilpivirine Fumarate obtained according to claim 1, wherein the Rilpivirine Fumarate is characterized by powder X-ray diffractogram having peaks at about 5.42, 9.32, 14.23, 15.19, 18.02, 18.78, 19.45, 23.17, 23.59, 23.99, 26.79, 27.99 ±0.2 θ ˚.

6. The crystalline Rilpivirine Malate obtained according to claim 1, wherein the Rilpivirine Malate is characterized by Powder X-ray diffraction pattern having peaks at about 5.52, 9.69, 12.41,14.79,18.31,19.63 ± 0.20°.

7. The crystalline Rilpivirine Maleate obtained according to claiml, wherein the Rilpivirine Maleate is characterized by Powder X-ray diffraction pattern having peaks at about 10.63, 13.37, 14.99, 15.23, 16.99, 18.39, 19.71, 21.05, 22.59, 22.92, 23.24, 25.18 ±0.2 θ ˚.

8. The crystalline Rilpivirine Tartarate obtained according to claim 1, wherein the Rilpivirine Tartarate is characterized by Powder X-ray diffraction pattern having peaks at about 5.19, 5.57, 9.85, 12.26, 15.01, 17.32, 17.92, 18.58, 19.70, 25.86 ± 0.2 θ ˚.

9. The crystalline Rilpivirine Saccharinate obtained according to claim 1^ wherein the Rilpivirine Saccharinate is characterized by Powder X-ray diffraction pattern having peaks at about 12.43, 12.80, 15.90, 16.74, 17.53, 19.09, 22.87, 23.72, 24.14, 24.97, ±0.2 θ ˚.

10. A pharmaceutical composition comprising the Rilpivirine organic acid addition salt wherein, organic acid addition salt is selected from Malonate, Succinate, Adipate, Fumarate, Malate, Maleate, Tartarate or Saccharinate.