WO2009034582A2

WO2009034582A2 - Process for the preparation of amorphous fexofenadine hydrochloride

Info

Publication number: WO2009034582A2
Application number: PCT/IN2008/000581
Authority: WO
Inventors: Chidambaram Venkateswaran Srinivasan; Perminder Singh Johar; Lalit Wadhwa
Original assignee: IND-SWIFT LABORATORIES Ltd; Ind Swift Laboratories Ltd
Current assignee: IND-SWIFT LABORATORIES Ltd; Ind Swift Laboratories Ltd
Priority date: 2007-09-13
Filing date: 2008-09-11
Publication date: 2009-03-19
Anticipated expiration: 2010-03-13
Also published as: WO2009034582A3

Abstract

The present invention provides a process for the preparation of amorphous fexofenadine hydrochloride from fexofenadine via its weak acid addition salt, in high yield and purity. The present invention further provides a process for the preparation of amorphous fexofenadine hydrochloride from fexofenadine acid addition salt.

Description

PROCESS FOR THE PREPARATION OF

AMORPHOUS FEXOFENADINE HYDROCHLORIDE

FIELD OF THE INVENTION

The present invention is directed towards process for the preparation of amorphous fexofenadine hydrochloride, a useful antihistamine drug.

BACKGROUND OF THE INVENTION

Fexofenadine hydrochloride having structural formula-I, is an Hj receptor antagonist and a useful antihistamine drug and is chemically known as 4-[4-[4-(hydroxydiphenylmethyl)-l- piperidinyl]-l-hydroxybutyl]-α,α-dimethylbenzene acetic acid hydrochloride.

Formula-I

Fexofenadine and pharmaceutically acceptable salts were first disclosed in US patent no. 4,254,129. According to the patent, fexofenadine can be prepared starting from ethyl, α,α- dimethylphenyl acetate and 4-chlorobutyroyl chloride, which are reacted under Friedel-Crafts conditions. Chloride is displaced from the Friedel-Crafts product with α,α-diphenyl-4- piperidine-methanol to give 4-[4-[4-(hydroxydiphenylmethyl)-l-piperidinyl]-l-oxobutyl]-α,α- dimethyl benzene acetate, which is isolated as its hydrochloride salt. The ketone is then reduced with PtOZH₂ and the ester group is hydrolyzed to yield fexofenadine and converted to its hydrochloride salt.

Other methods of preparing fexofenadine are discussed in US patents 5,578,610, 5,589,487, 5,581,011, 5,663,412, 5,750,703, 5,994,549, 5,618,940, 5,631,375, 5,644,061, 5,650,516, 5,652,370, 5,654,433, 5,663,353, 5,675,009, 5,375,693 and 6,147,216.

US patents 5,738,872, 5,932,247 and 5,855,912, describe four crystal forms of fexofenadine hydrochloride which are designated as Forms I-IV. According to the aforesaid patents, Forms II and IV are hydrates and Forms I and III are anhydrates. Each form is characterized by its melting point, onset of endotherm in the DSC profile, and PXRD. The patent further discusses methods of interconverting Forms I-IV. Aqueous recrystallization of Form I can be used to produce Form II. Water-minimizing recrystallization or azeotropic distillation of either Form II or Form IV can yield Form I. Form III is reported to be accessible by water minimizing recrystallization of Form II. Crystal digestion of Form III can be used to obtain Form I. The above crystalline forms are also disclosed in the PCT publication WO 95/31437.

PCT publication WO 2000/71124 Al, describes a process for the preparation of amorphous fexofenadine hydrochloride by lyophilizing or spray drying a solution of fexofenadine hydrochloride.

US Patent Application 2003/0021849 describes a process for preparing amorphous fexofenadine hydrochloride by preparing a solution of fexofenadine hydrochloride in tetrahydrofuran (THF); removing a portion of THF from the solution; adding a C₅ to C₁₂ saturated hydrocarbon to THF to form layers; separating and drying the lower layer to obtain amorphous fexofenadine. According to the said application amorphous fexofenadine hydrochloride can also be prepared by preparing a solution of fexofenadine hydrochloride in an organic solvent and removing the solvent by evaporating under ambient or reduced pressure.

US Patent Application 2005/0165056 describes a process for preparing non-hydrated amorphous fexofenadine hydrochloride wherein fexofenadine base in a solvent such as heptane or tert-butyl methyl ether is treated with a solution of hydrogen chloride in isopropyl ether.

US Patent Application 2005/0256163 describes a process for preparing amorphous fexofenadine hydrochloride by heating crystalline fexofenadine hydrochloride form XVI at 80-100 °C.

All the known processes in the prior art have some advantage/disadvantages over each other. Thus, there is a widely recognized need to develop a highly advantageous process for the preparation of stable amorphous form of fexofenadine hydrochloride in a simple manner, without the need for tedious operations such as spray drying or freeze drying.

The present invention provides a process for the preparation of highly pure amorphous fexofenadine hydrochloride from fexofenadine via its acid addition salts using conditions which are convenient to operate on a commercial scale and are operationally safe. OBJECT QF THE INVENTION

The principal object of the present invention is to provide an industrially advantageous process for the preparation of highly pure fexofenadine hydrochloride in amorphous form that is cost effective, eco-friendly, commercially viable as well as reproducible on industrial scale.

One another object of the present invention is to provide a process for the preparation of amorphous fexofenadine hydrochloride from fexofenadine via its acid addition salts.

Yet another object of the present invention is to provide a process for the preparation of amorphous fexofenadine hydrochloride from fexofenadine acid addition salts.

SUMMARY OF THE INVENTION

The present invention encompasses an efficient and industrially advantageous process for the preparation of amorphous fexofenadine hydrochloride of formula I,

Formula-I

from fexofenadine via its acid addition salt, in high yield and purity.

According to one embodiment, the present invention provides a process for the preparation of amorphous fexofenadine hydrochloride, comprises the steps of:

a) providing a solution of fexofenadine in a suitable solvent; b) reacting the solution with an appropriate acid to form fexofenadine acid addition salt; c) optionally, isolating the fexofenadine acid addition salt; d) treating the same with a source of hydrogen chloride for a time sufficient to convert acid addition salt to hydrochloride salt; and e) isolating the amorphous fexofenadine hydrochloride. According to another embodiment, the present invention provides a process for the preparation of amorphous fexofenadine hydrochloride starting from fexofenadine acid addition salts, which comprises:

a) providing a solution of fexofenadine acid addition salt; b) treating the solution with a source of hydrogen chloride for a time sufficient to convert acid addition salt to hydrochloride salt; and c) isolating the amorphous fexofenadine hydrochloride.

According to yet another embodiment, the present invention also provides novel acid addition salts of fexofenadine.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1. illustrates the powdered X-ray diffraction pattern of fexofenadine formate.

Figure 2. illustrates the powdered X-ray diffraction pattern of amorphous fexofenadine hydrochloride.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides an industrially advantageous process for the preparation of highly pure amorphous fexofenadine hydrochloride.

According to one embodiment, the present invention provides a process for the preparation of amorphous fexofenadine hydrochloride from fexofenadine via its acid addition salts in high yield and purity.

Generally, fexofenadine is dissolved in a suitable solvent followed by addition of appropriate acid to form fexofenadine acid addition salt. The reaction mass is stirred for few minutes to few hours at ambient temperature to reflux temperature of the solvent. Preferably, the reaction mixture is stirred at 25-30 ⁰C for one hour, more preferably reaction mixture is stirred till the completion of the reaction. To affect the dissolution, the solution of fexofenadine in a suitable solvent may optionally be heated. The suitable solvent can be selected from aromatic hydrocarbon; cyclic or acyclic straight chain or branched Ci-Cj₂ ether, preferably Ci-C₆ ether; straight chain or branched saturated or unsaturated Cj-C₆ alcohol; halogenated solvent; dialkoxy ethane; nitriles; ester of general formula RiCOOR wherein R and Ri are individually selected from a straight chain or branched Ci-Ce alkyl group, preferably ester of general formula CH₃COOR wherein R is as defined above; C₁-C₈ ketones and the like or mixtures thereof. Preferably the solvent can be selected from toluene, xylene, ethylbenzene, tetrahydrofuran, dioxane, methanol, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, dimethoxy ethane, acetonitrile, propionitrile, butyronitrile, isobutyronitrile, ethyl acetate, isopropyl acetate, n-butyl acetate, the like and mixtures thereof. The appropriate acid include weak carboxylic acid such as formic acid; C_2-10 carboxylic acid; substituted or unsubstituted dicarboxylic acid; substituted or unsubstituted tri-carboxylic acid; ascorbic acid; tere-phthalic acid; unsubstituted or substituted benzoic acid (preferably substituted with groups selected from halo, alkoxy, nitro, thioalkoxy, hydroxyl) and the like. The acid is preferably selected from propanoic acid, butanoic acid, pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, lactic acid, succinic acid, fumaric acid, maleic acid, phthalic acid, isophthalic acid, citric acid, ascorbic acid, tere-phthalic acid and the like. Similar organic and inorganic acids well known in art can equally be employed in the reaction and may be obvious to the person skilled in the art.

The fexofenadine acid addition salt can optionally be isolated by suitable techniques such as filtration, evaporation, distillation, vacuum drying, centrifugation and the like. Fexofenadine acid addition salt, if desired can be treated with a suitable solvent to remove certain unidentified impurities present in the product. The process involves dissolving the fexofenadine acid addition salt in a suitable solvent at a temperature of 25 ⁰C to reflux temperature of solvent for few minutes to few hours, preferably reaction mixture is heated at the reflux temperature of solvent for a period of 1 to 5 hours. More preferably the mixture is heated for 2 hours. Suitable solvent include C₂-Ci_O ethers, Ci-Cio esters, C₃-C₁₀ ketones or mixture thereof, preferably the solvent is tetrahydrofuran. The fexofenadine acid addition salt is then isolated from the reaction mixture by suitable techniques same as described above. The fexofenadine acid addition salt thus isolated is free from certain unidentified impurities. The isolated fexofenadine acid addition salt so obtained is then converted to amorphous fexofenadine hydrochloride.

Alternatively, the amorphous fexofenadine hydrochloride can be prepared from fexofenadine directly through in situ fexofenadine acid addition salt formation; that is without the isolation of acid addition salt of fexofenadine.

Fexofenadine acid addition salt in a suitable organic solvent or the reaction mixture containing the fexofenadine acid addition salt is treated with a source of hydrogen chloride for a time sufficient to convert it to amorphous fexofenadine hydrochloride, preferably till the pH 1 to 6.5 is attained, more preferably pH of the reaction mixture is 2 to 3. The suitable organic solvent is as described above. The source of hydrogen chloride can be selected from gaseous hydrogen chloride or hydrochloric acid in a mixture with a solvent which includes but not limited to alcoholic hydrochloride preferably methanolic hydrochloride, ethanolic hydrochloride, isopropanolic hydrochloride; ethereal hydrochloride preferably isopropylether hydrochloride; toluene hydrochloride; ethyl acetate hydrochloride and the like. Ratio of fexofenadine acid' addition salt to solvent is adjusted to about 1 :2-6, preferably 1 :4-5.

Amorphous fexofenadine hydrochloride can be isolated from the reaction mixture by suitable techniques such as filtration, centrifugation, decantation, precipitation and the like. Preferably, amorphous fexofenadine hydrochloride is isolated from the reaction mixture by adding an antisolvent to the solution. Preferably the antisolvent can be selected from solvent capable of inducing precipitation of amorphous fexofenadine hydrochloride. Antisolvent include, but not limited to aromatic or aliphatic hydrocarbon; straight chain or branched C₁-C₆ ether and the like or mixture thereof. Preferably the anti solvent can be selected from isopropylether, pentane, hexane, cyclohexane, n-heptane, toluene, xylene, ethyl benzene and the like or mixtures thereof. The reaction can be conducted at a temperature of about -10 ⁰C to ambient temperature followed by the isolation of amorphous fexofenadine hydrochloride in high yields and purity.

The acid addition salts of fexofenadine are preferably isolated as crystalline salts, and further form the inventive part of the invention. Fexofenadine acid addition salt can be characterized by at least one of mass spectra (MS), X-ray diffraction spectroscopy (XRD), infra-red spectroscopy (IR), ¹H or ¹³C Nuclear magnetic resonance spectroscopy (NMR) or differential scanning calorimetry (DSC).

Formate salt of fexofenadine so obtained by the process of the present invention is characterized by XRD pattern as shown in Figure. 1.

However, it is to be understood that the X-ray diffraction (XRD) patterns reported as absolute positions in the figures are intended to include the normal amount of positional variation due to experimental error, operator error, differences in equipment, technique, packing, contamination, and the like. However, based on this technique, particularly in conjugation with other techniques like infra red spectra and endotherm, one of ordinary skill in this art will be able to identify whether or not a compound is fexofenadine acid addition salt in accordance with the present invention. It should be kept in mind that slight variations in the observed 2Θ angles values are expected, based on the specific diffractometer employed, the analyst, and the sample preparation techniques. More variation is expected for the relative peak intensities, which is largely affected by particle size of the sample. Thus, identification of exact crystalline form of a compound should be based primarily on observed 2Θ angles with lesser importance attributed to relative peak intensities. The fexofenadine acid addition salt is then converted to amorphous fexofenadine hydrochloride.

According to another embodiment, the present invention provides a process for the preparation of fexofenadine hydrochloride from acid addition salt of fexofenadine.

Generally, the reaction involves the treatment of fexofenadine acid addition salt in a suitable organic solvent with a source of hydrogen chloride for a time sufficient to convert it to amorphous fexofenadine hydrochloride. Preferably, the mixture is treated with a source of hydrogen chloride till the pH of the reaction mixture ranges from 1 to 6.5, more preferably pH of the reaction mixture is 2 to 3. Acid addition salt includes those as defined above. The suitable solvent can be selected from aromatic hydrocarbon; cyclic or acyclic straight chain or branched C₁-C₁₂ ether, preferably C₁-C₆ ether; straight chain or branched saturated or unsaturated C₁-C₆ alcohol; halogenated solvent; dialkoxy ethane; nitriles; ester of general formula Rj COOR wherein R and Ri are selected independently from straight chain or branched Ci-Ce alkyl group, preferably ester of general formula CH₃COOR wherein R is as defined above; Ci-C₈ ketones and the like or mixtures thereof. Preferably the solvent can be selected from toluene, xylene, ethylbenzene, tetrahydrofuran, dioxane, methanol, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, dimethoxy ethane, acetonitrile, propionitrile, butyronitrile, isobutyronitrile, ethyl acetate, isopropyl acetate, n-butyl acetate, the like and mixtures thereof.

The source of hydrogen chloride can be selected from dry gaseous hydrogen chloride or hydrochloric acid in a mixture with a solvent. Preferably acid addition salt of fexofenadine in a suitable organic solvent is combined with hydrochloric acid in mixture with solvent which includes, but not limited to methanolic hydrochloride, ethanolic hydrochloride, isopropanolic hydrochloride; ethereal hydrochloride preferably isopropylether hydrochloride; toluene hydrochloride; ethyl acetate hydrochloride and the like. Ratio of fexofenadine acid addition salt to solvent is adjusted to about 1:2-6, preferably 1:4-5.

Alternatively, the conversion of acid addition salt of fexofenadine to fexofenadine hydrochloride can also be conducted by passing dry hydrogen chloride gas through the reaction mixture till a pH of2-3. Amorphous fexofenadine hydrochloride can be isolated from the reaction mixture by suitable techniques such as filtration, centrifugation, decantation, precipitation and the like. Preferably, amorphous fexofenadine hydrochloride is isolated from the reaction mixture by adding an antisolvent to the reaction mixture. The antisolvent is same as defined above.

The amorphqus fexofenadine hydrochloride so formed by the process of the present invention can be characterized by at least one of mass spectra (MS), X-ray diffraction spectroscopy (XRD), infra-red spectroscopy (IR), ¹H or ¹³C Nuclear magnetic resonance spectroscopy (NMR) or differential scanning calorimetry (DSC).

The amorphous fexofenadine hydrochloride is characterized by X-ray diffraction pattern as shown in figure 2. X-ray diffraction is measured on a PANalytical X'Pert Pro diffractometer with Cu radiation and expressed in terms of two-theta, d-spacings and relative intensities. Ordinarily, one skilled in the art understands that experimental differences may arise due to differences in instrumentation, sample preparation or other factors.

All infrared measurements are made on Perkin Elmer Spectrum 100 spectrometer using KBr pellets having the characteristic absorption bands expressed in reciprocal centimeter.

Melting point is conducted using a Polmon MP Apparatus with a sample weight of about 10 mg. DSC analysis is performed using a Mettler Toledo 823^e. Thermal weight change measurements were made on a Mettler TG5O Thermogravimetric Analyzer.

Although, the following examples illustrate the practice of the present invention in some of its embodiments, the examples should not be construed as limiting the scope of the invention.

EXAMPLES

Example 1: Preparation of fexofenadine formate

To a mixture of fexofenadine (100 g) in tetrahydrofuran (2 It), formic acid (85 %, 11.1 g) was added and stirred for one hour at 25-30 ⁰C. The precipitated fexofenadine formate salt was filtered, washed with tetrahydrofuran, and dried to obtain 97 g of title compound. Example 2: Preparation of fexofenadine formate

To a mixture of fexofenadine (100 g) in tetrahydrofuran (2 It), formic acid (99 %, 9.64 g) was added and stirred for one hour at 25-30 ⁰C. The precipitated product was filtered, washed with tetrahydrofuran, and dried to obtain 97 g of title compound.

Example 3: Preparation of fexofenadine formate

To a mixture of fexofenadine (50 g) in dichloromethane (250 ml) was added formic acid (99 %, 4.82 g) and stirred for 12 hours at 25-30 ⁰C. The precipitated formate salt was filtered, washed with dichloromethane, and dried to obtain 49 g of title compound.

Example 4: Preparation of fexofenadine formate

To a mixture of fexofenadine (450 g) in tetrahydrofuran ( 6.75 It), formic acid (85 %,_.49.6 g) was added and stirred for 2 hours at 25-30 ⁰C. The precipitated solid was filtered, washed with tetrahydrofuran (900 ml) and dried at 60-65 ⁰C under vacuum to obtain 450 g of title compound.

Tetrahydrofuran (4.5 It) was added to compound obtained above and refluxed for 2 hours. Reaction mixture was cooled to 25-30 ⁰C and filtered. The Resulting product was washed with tetrahydrofuran (900 ml) and dried at 60-65 ⁰C under vacuum to obtain 415 g of title compound.

Example 5: Preparation of amorphous fexofenadine hydrochloride

To the solution of fexofenadine formate salt (50 g) in isopropylether (250 ml) was added isopropylether-hydrochloride (99 ml) at 5-10 ⁰C and the reaction mass was stirred for one hour at the same temperature. The product was filtered, washed with isopropylether (50 ml), and dried to obtain 48 g of title compound.

Example 6: Preparation of amorphous fexofenadine hydrochloride

To the solution of fexofenadine formate salt (5 g) in tetrahydrofuran (20 ml) was added isopropylether-hydrochloride (5 ml) at 5-10 ⁰C and stirred for 30 minutes. To the reaction mixture isopropyl ether (50 ml) was added and the reaction mixture was stirred for further one hour at the same temperature. The product was filtered, washed with isopropylether (50 ml), and dried to obtain 3.2 g of title compound. Example 7: Preparation of amorphous fexofenadine hydrochloride

To the solution of fexofenadine formate salt (25 g) in ethyl acetate (125 ml) was added isopropylether-hydrochloride (6.2 %, 32 ml) at 5-10 ⁰C. Isopropyl ether (93 ml) was added to the reaction mixture and further stirred for 30 minutes at the same temperature. The product was filtered, washed with isopropyl ether (50 ml), and dried to obtain 22.5 g of title compound.

Example 8: Preparation of amorphous fexofenadine hydrochloride

To the solution of fexofenadine formate salt (50 g) in methanol (250 ml) was added methanol- hydrochloride (34 ml) at 0 to -5 ⁰C and stirred for 20 minutes at 0 ⁰C. The temperature was raised to 20 - 25 ⁰C and thereafter methanol was distilled off completely in vacuum. Isopropyl ether (250ml) was added and stirred at 25 to 30 ⁰C for 1 hour. The reaction mixture was filtered, washed with isopropyl ether (50 ml) and dried to obtain 47.3 g of title compound having purity 99.8 % by HPLC.

Example 9: Preparation of amorphous fexofenadine hydrochloride

A solution of fexofenadine formate salt (100 g) in methanol (500 ml) was cooled to 0-5 ⁰C followed by addition of a mixture of methanolic- hydrochloride (13 %, 46 ml) and methanol (46 ml) at 0 to 5 ⁰C. Thereafter the pH of the mixture was adjusted to 4 to 5 followed by stirring at

0 ⁰C. Methanol was distilled off completely at 35 - 42 ⁰C under vacuum. Isopropyl ether (500 ml) was added to the reaction mixture arid stirred at 25 to 30 ⁰C for one hour. The reaction mixture was filtered, washed with isopropylether (500 ml) and dried to obtain 82.5 g of title compound having purity 99.95 % by HPLC. Moisture content = 0.4 %; Chloride content = 6.44

%. PXRD shows it to be amorphous.

Example 10: Preparation of amorphous fexofenadine hydrochloride

To a solution of fexofenadine (10 g) in acetonitrile (50 ml) was added formic acid (99 %, 0.96 g) and stirred for 2 hour at 25-30 ⁰C. The reaction mixture was cooled to 0 ⁰C and dry hydrochloric acid gas was passed through it till pH of 2-3. The solvent was distilled off and n- heptane (50 ml) was added and stirred for 1 hour, filtered and dried to obtain 8.5 g of title compound.

Claims

WE CLAIM

1. A process for the preparation of amorphous fexofenadine hydrochloride, comprises the steps of:

a) providing a solution of fexofenadine in a suitable solvent; b) reacting the solution with an appropriate acid to form fexofenadine acid addition salt; c) optionally, isolating the fexofenadine acid addition salt; d) treating the same with a source of hydrogen chloride for a time sufficient to convert acid addition salt to hydrochloride salt; and e) isolating the amorphous fexofenadine hydrochloride.

2. The process according to claim 1, wherein in step a) suitable solvent include aromatic hydrocarbon, cyclic or acyclic straight chain or branched C₁-C₁₂ ether, straight chain or branched saturated or unsaturated C₁-C₆ alcohol, halogenated solvent, dialkoxy ethane, nitriles, ester of general formula R₁COOR wherein R and Ri are individually selected from a straight chain or branched Ci-Ce alkyl group, C₁-C₈ ketones or mixtures thereof.

3. The process according to claim 1, wherein step a) suitable solvent is selected from Cj-C₆ ether, ester of general formula CH₃COOR wherein R is as defined above and the like or mixture thereof.

4. The process according to claim 1, wherein step a) suitable solvent is selected from toluene, xylene, ethylbenzene, tetrahydrofuran, dioxane, methanol, dichloromethane, chloroform, dichloroethane, carbon tetrachloride, dimethoxy ethane, acetonitrile, propionitrile, butyronitrile, isobutyronitrile, ethyl acetate, isopropyl acetate, n-butyl acetate and the like or mixture thereof.

5. The process according to claim 1, wherein in step b) appropriate acid include organic or inorganic acid.

6. The process according to ^claim 5, organic acid include weak carboxylic acid, C_2-I0 carboxylic acid, substituted or unsubstituted dicarboxylic acid, substituted or unsubstituted tri-carboxylic acid, ascorbic acid, tere-phthalic acid, unsubstituted or substituted benzoic acid (preferably substituted with groups selected from halo, alkoxy, nitro, thioalkoxy, hydroxyl) and the like.

7. The process according to claim 5, organic acid is selected from formic acid, propanoic acid, butanoic acid, pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, lactic acid, succinic acid, fumaric acid, maleic acid, phthalic acid, isophthalic acid, citric acid, ascorbic acid, tere-phthalic acid and the like.

8. The process according to claim 1, wherein fexofenadine acid addition salt isolated in step c) is optionally purified with a suitable solvent.

9. The process according to claim 8, suitable solvent includes C₂-C₁₀ ethers, Ci-Ci₀ esters, C₃- ■ Cio ketones.

10. The process according to claim 8, suitable solvent is tetrahydrofuran.

11. The process according to claim 1, wherein step d) source of hydrogen chloride is gaseous hydrogen chloride or hydrochloric acid in mixture with a solvent.

12. The process according to claim 11, gaseous hydrogen chloride in mixture with a solvent includes alcoholic hydrochloride, ethereal hydrochloride, toluene hydrochloride, ethyl acetate hydrochloride and the like.

13. The process according to claim 11 , gaseous hydrogen chloride in mixture with a solvent is selected from methanolic hydrochloride, ethanolic hydrochloride, isopropanolic hydrochloride, isopropylether hydrochloride, ethyl acetate hydrochloride, toluene hydrochloride and the like.

14. The process according to claim 1, wherein in step e) isolation is carried out by adding an antisolvent to the treated solution in an amount sufficient to precipitate amorphous fexofenadine hydrochloride.

15. The process according to claim 14, wherein antisolvent include aromatic or aliphatic hydrocarbon, straight chain or branched Ci-C₆ ether and the like or mixture thereof.

16. The process according to claim 14, wherein antisolvent is selected from pentane, hexane, cyclohexane, n-heptane, toluene, xylene, ethyl benzene, isopropylether and the like or mixture thereof.

17. A process for the preparation of amorphous fexofenadine hydrochloride, comprises the steps of:

a) providing a solution of fexofenadine acid addition salt in a suitable solvent; b) treating the solution with a source of hydrogen chloride for a time sufficient to convert acid addition salt to hydrochloride salt; and c) isolating the amorphous fexofenadine hydrochloride.

18. The process according to claim 17, wherein in step a) suitable solvent include aromatic hydrocarbon; cyclic or acyclic straight chain or branched Cj-Ci₂ ether; straight chain or branched saturated or unsaturated Ci-C₆ alcohol, halogenated solvent, dialkoxy ethane, nitriles, ester of general formula RiCOOR wherein R and Ri are individually selected from a straight chain or branched Ci-C^ alkyl group, Ci-Cg ketones or mixtures thereof.

19. The process according to claim 17, wherein in step a) solvent is selected from Cj-C₆ ether, ester of general formula CH₃COOR wherein R is as defined above and the like or mixture thereof.

20. The process according to claim 17, wherein in step a) suitable solvent is selected from toluene, xylene, ethylbenzene, tetrahydrofuran, dioxane, methanol, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, dimethoxy ethane, acetonitrile, propionitrile, butyronitrile, isobutyronitrile, ethyl acetate, isopropyl acetate, n-butyl acetate and the like or mixture thereof.

21. The process according to claim 17, wherein in step b) source of hydrogen chloride include gaseous hydrogen chloride or hydrochloric acid in mixture with a solvent.

22. The process according to claim 21, wherein gaseous hydrogen chloride in mixture with a solvent include alcoholic hydrochloride, ethereal hydrochloride, toluene hydrochloride, ethyl acetate hydrochloride and the like.

23. The process according to claim 21, wherein gaseous hydrogen chloride in mixture with a solvent is selected from methanolic hydrochloride, ethanolic hydrochloride, isopropanolic hydrochloride, isopropylether hydrochloride, ethyl acetate hydrochloride, toluene hydrochloride and the like.

24. The process according to claim 17, wherein in step c) isolation is carried out by adding an antisolvent to the treated solution in an amount sufficient to precipitate amorphous fexofenadine hydrochloride.

25. The process according to claim 24, wherein antisolvent include aromatic or aliphatic hydrocarbon, straight chain or branched Cj-C₆ ether and the like or mixture thereof.

26. The process according to claim 24, wherein antisolvent is selected from pentane, hexane, cyclohexane, n-heptane, toluene, xylene, ethyl benzene, isopropylether and the like or mixture thereof.

27. Fexofenadine acid addition salt.

28. Fexofenadine formate.

29. Crystalline fexofenadine formate.

30. The crystalline fexofenadine formate according to claim 29, has characteristic X-ray powder diffraction pattern as given in figure 1.

31. A process for preparing fexofenadine acid addition salt comprises the steps of:

a) providing a solution of fexofenadine in a suitable solvent; b) reacting the solution with appropriate acid to form fexofenadine acid addition salt; c) isolating the fexofenadine acid addition salt; and d) optionally, purifying with suitable solvent.

32. The process according to claim 31 , wherein in step a) suitable solvent include aromatic hydrocarbon, cyclic or acyclic straight chain or branched Ci-C₁₂ ether, straight chain or branched saturated or unsaturated C₁-C₆ alcohol, halogenated solvent, dialkoxy ethane, nitriles, ester of general formula RiCOOR wherein R and Ri are individually selected from a straight chain or branched C]-Ce altyl group, C₁-C₈ ketones or mixtures thereof.

33. The process according to claim 31, wherein in step a) suitable solvent is selected from C₁-C₆ ether, ester of general formula CH₃COOR wherein R is as defined above and the like or mixture thereof.

34. The process according to claim 31, wherein in step a) suitable solvent is selected from toluene, xylene, ethylbenzene, such as tetrahydrofuran, dioxane, methanol, dichloromethane, chloroform, dichloroethane, carbon tetrachloride, dimethoxy ethane, acetonitrile, propionitrile, butyronitrile, isobutyronitrile, ethyl acetate, isopropyl acetate, n-butyl acetate and the like or mixture thereof.

35. The process according to claim 31, wherein in step b) appropriate acid include organic or inorganic acid.

36. The process according to claim 35, wherein organic acid include weak carboxylic acid, C_2-10 carboxylic acid, substituted or unsubstituted dicarboxylic acid, substituted or unsubstituted tri-carboxylic acid, ascorbic acid, tere-phthalic acid, unsubstituted or substituted benzoic acid (preferably substituted with groups selected from halo, alkoxy, nitro, thioalkoxy, hydroxyl), and the like.

37. The process according to claim 35, wherein organic acid is selected from formic acid, propanoic acid, butanoic acid, pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, lactic acid, succinic acid, fumaric acid, maleic acid, phthalic acid, isophthalic acid, citric acid, ascorbic acid, ter-phthalic acid and the like.

38. The process according to claim 31, wherein in step d) suitable solvent includes C₂-Ci₀ ethers, Ci-Cio esters, C₃-Ci₀ ketones or mixture thereof.

39. The process according to claim 31, wherein in step d) suitable solvent is tetrahydrofuran.

40. The process according to claim 31, wherein fexofenadine acid addition salt is fexofenadine formate.