WO2007063556A2

WO2007063556A2 - An improved and industrial process for the preparation of alfuzosin hydrochloride and its novel polymorphs

Info

Publication number: WO2007063556A2
Application number: PCT/IN2007/000019
Authority: WO
Inventors: Manne Satyanarayana Reddy; Muppa Kishore Kumar; Bairy Kondal Reddy; Mummadi Venkatesh
Original assignee: Msn Laboratories Limited
Priority date: 2006-12-07
Filing date: 2007-01-19
Publication date: 2007-06-07
Also published as: WO2007063556A3

Abstract

An improved and industrial process for the preparation of Alfuzosin Hydrochloride and its novel polymorphs (Formula (I)).

Description

Improved and Industrial Process for the Preparation of Alfuzosin Hydrochloride and Its Novel Polymorphs

Field of the Invention:

The present invention relates to an improved and industrial process for the preparation of Alfuzosin hydrochloride and also relates to Novel polymorphs of Alfuzosin hydrochloride.

Formula (I)

Alfuzosin is a selective antagonist of post-synaptic αradrenoreceptors which are located in the prostate, bladder base bladder neck, prostatic capsule, and prostatic urethtra. Alfuzosin hydrochloride is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia and is sold under the brand name Uroxatral.

Background of the Invention:

US Patent 4,315,007 claims Alfuzosin and its pharmaceutically acceptable salt and method of treating a cardiovascular disorder. The US Patent 4,315,007 discloses a process for the preparation of Alfuzosin hydrochloride in two synthetic schemes, which comprises the reaction of 4-amino-2-chloro-6,7-dimethoxyquinazoline and 3- methylamino propionitrile gives N-(4-amino-6,7-dimethoxyquinazol-2-yl)-N- mehtylpropionitrile which on reduction with Raney Ni gives Nl-(4-amino-6,7- dimethoxyquinazol-2-yl)Nl-methylpropylene diamine. This diamine condenses with carbonyl diimidazole derivative of tetrahydrofuroic acid to give Alfuzosin hydrochloride.

The main drawback of the above said process is that the Alfuzosin hydrochloride was recrystallized in a mixture of ethanol and ether solvents. Those solvents are not recommendable for commercial scale-up. Another synthetic scheme of US Patent 4,315,007 comprises reaction of tetrahydro-2-furoicacid with ethyl chloroformate in presence of triethylamine further with 3-(methylamino)-propionitrile to give 2-cyano-N-methyl-N-tetrahydrofuroylamine. Reduction of this nitrile in presence of rhodium on alumina gives Nl-methyl-N2- tetrahydrofuroyl propylene diamine. The resulted diamine condenses with 4-amino-2- chloro-6,7-dimethoxyquinazoline gives Alfuzosin hydrochloride.

The drawback of the above said process is that the said process involves reduction of nitrile compound in presence of rhodium on alumina forms unwanted isomer (Ref. JMC, 1986, Vol.29, No.l) and also the usage of expensive reagent like rhodium on alumina which is commercially not recommendable.

The EP patent 0179689 Bl also discloses the process for the preparation of alkylene diamines (i.e., Alfuzosin hydrochloride), which comprises reaction of tetrahydrofuroic acid methyl ester and 3-methylamino propane 1,3 diamine gives Nl- methyl-N2-tetrahydrofuroyl propylene diamine. The resulted diamine condenses with 4- amino-2-chloro-6,7-dimethoxyquinazoline to give Alfuzosin hydrochloride.

The US 5545738 patent claims dihydrate form of Alfuzosin hydrochloride and discloses process for the preparation of anhydrous, monohydrate, dihydrate, trihydrate and tetrahydrate forms of Alfuzosin hydrochloride.

WO 2006/030449 patent publication claimed the crystalline Alfuzosin base and process for preparing the same. The process involves dissolving the impure Alfuzosin base in a keto or alcoholic solvent and crystallizing the Alfuzosin base from solution.

WO 2006/090268 patent publication claimed polymorph Form A of Alfuzosin, polymorphic Form-I and Form-II of Alfuzosin hydrochloride and process for preparing the same.

All the prior art processes for the preparation Alfuzosin base leads to the formation of crystalline compound having melting range of about 178-182°C. Alfuzosin base compound melting range (i.e., 178-182⁰C) has been disclosed in table-1, column 7 of US Patent No. 5503843.

The main objective of the present invention is to provide an improved and industrial process for the preparation of Alfuzosin hydrochloride. The second aspect of the invention is to provide an improved and industrial process for the preparation of non-solvated crystalline form of Alfuzosin hydrochloride.

The third aspect of the invention is to provide an isopropyl alcohol solvated form of Alfuzosin hydrochloride and process for preparing the same.

The fourth aspect of the invention is to provide an amorphous form of Alfuzosin hydrochloride and process preparing the same.

Brief description of the Invention

Accordingly the first aspect of the present invention provides an improved and industrial process for the preparation of Alfuzosin hydrochloride, chemically known as N₁-(4-amino-6,7-dimethoxyqumazol-2-yl)-N₁-methyl-N₂-(tetrahydrofuroyl-2)- propylenediamine hydrochloride compound of formula- 1.

Formula- 1

Improved and Industrial process for the preparation of Alfuzosin hydrochloride compound of formula- 1 comprises of the following steps a) Reacting an acid compound of formula-2 with methanol in presence of a suitable acid catalyst to give ester compound of formula-3, which in-situ reacting with diamine compound of formula-4 in a suitable solvent to give amide compound of formula-5, b) Reacting the amide compound of formula-5 with quinazoline compound of formula-6 in a suitable organic solvent to give Alfuzosin compound of formula-7, c) Purifying Alfuzosin compound of formula-7 by using a suitable solvent selected from alcoholic solvents and/or keto solvents and/or ester solvents and/or chloro solvents, d) Converting the Alfuzosin compound of formula-7 into Alfuzosin hydrochloride compound of formula- 1 by treating with suitable alcoholic hydrochloric acid in a suitable solvent.

The second aspect of the present invention provides an improved and industrial process for the preparation of non-solvated crystalline form of Alfuzosin hydrochloride compound of formula- 1 comprises of the following steps a) Reacting Alfuzosin compound of formula-7 with suitable alcoholic hydrochloric acid in a suitable solvent, b) Isolating the Alfuzosin hydrochloride by adding a suitable anti-solvents, c) Slurrying the above obtained wet Alfuzosin hydrochloride in a suitable solvent, d) Separating the solid by filtration and drying the material to get the non-solvated crystalline form of Alfuzosin hydrochloride compound of formula- 1.

The third aspect of the present invention is to provide isopropyl alcohol solvated form of Alfuzosin hydrochloride and process for preparing the same, which comprises of a) Adding alcoholic hydrochloride to a mixture of Alfuzosin base compound of formula-7 in a suitable solvent, b) Isolating the solvated form of Alfuzosin hydrochloride by adding a suitable anti solvent.

The fourth aspect of the present invention is to provide a novel amorphous form of Alfuzosin hydrochloride and process for preparing the same, which comprises of a) Adding alcoholic hydrochloride to the compound of formula-7 in a suitable solvent, b) distilling the solvent to dryness to get the amorphous form of Alfuzosin hydrochloride.

The process of the present invention is simple, cost effective environment friendly and commercially suitable over the prior art references. Brief Description of the Drawings

Figure-1: Illustrates powder X-ray diffraction pattern of Non-solvated crystalline form of

Alfuzosin hydrochloride.

Figure-2: Illustrates IR spectrum of Non-solvated crystalline form of Alfuzosin hydrochloride.

Figure-3: Illustrates DSC of Non-solvated crystalline form of Alfuzosin hydrochloride.

Figure-4: Illustrates GC chromatogram (i.e., RS/OVI) of Non-solvated crystalline form of Alfuzosin hydrochloride

Figure-5: Illustrates XRD of amorphous form of Alfuzosin hydrochloride

Figure-6: Illustrates GC chromatogram (i.e.,RS/OVI) of Isopropyl alcohol solvated form of Alfuzosin hydrochloride

Detailed description of the invention:

The first aspect of the present invention provides an improved and industrial process for the preparation of Alfuzosin hydrochloride, chemically known as N₁-(4-amino-6,7-dimethoxyquinazol-2-yl)-N₁-methyl-N₂-(tetrahydrofuroyl-2)- propylenediamine hydrochloride compound of formula- 1,

Formula- 1

Which comprises of the following steps a) Reacting an acid compound of formula-2

Formula-2 with suitable alcohol such as methanol in presence of a suitable acid catalyst such as sulphuric acid to give ester compound of formula-3, which in-situ reacting with diamine compound of formula-4 in a suitable alcoholic solvent like methanol to give amide compound of formula-5,

Formula-5 b) Reacting amide compound of formula-5 with quinazoline compound of formula-6

Formula-6 in a suitable solvents selected from the solvents like C₁-C₅ alcohols, toluene, acetone, Xylene, sulfolane, isoamylalcohol and dimethylformamide preferably sulfolane and isoamylalcohol, most preferably isoamylalcohol at a temperature ranges from 35°C to reflux temperature of the solvent to give the Alfuzosin compound of formula-7,

Formula-7 c) Purifying the compound of formula-7 by using alcoholic solvents like methanol, ethanol, isopropyl alcohol and propanol and/or keto solvents like acetone, methylisobutylketone, methylethylketone and/or nitrile solvents like acetonitrile and/or ester solvents like ethyl acetate, methyl acetate, isopropyl acetate and methyl isopropyl acetate and/or chloro solvents like methylene chloride and chloroform preferably chloro solvents and ester solvents, most preferably ester solvents such as ethyl acetate, d) Reacting the compound of formula-7 with suitable alcoholic hydrochloric acid selected from methanolic hydrochloric acid, isopropanolic hydrochloric acid or ester hydrochloric acid such as ethyl acetate hydrochloric acid preferably methanolic hydrochloric acid in a suitable organic solvents selected from C_1-C₄ alcohols and isolating the Alfuzosin hydrochloride compound of formula- 1 by adding the reaction mixture to suitable anti-solvents selected from the solvents like ethylacetate, methylacetate, isopropyl acetate, methyl isopropyl acetate, toluene, cyclohexane and n-heptane at a temperature of from 0°C to reflux temperature of the solvent used.

The second aspect of the present invention is to provide an improved and industrial process for the preparation of non-solvated crystalline form of Alfuzosin hydrochloride, which comprises of the following steps, a) Reacting the Alfuzosin compound of formula-7 with suitable alcoholic hydrochloric acid selected from methanolic hydrochloric acid, isopropanolic hydrochloric acid or ester hydrochloric acid such as ethyl acetate hydrochloric acid preferably methanolic hydrochloric acid in a suitable organic solvents selected from C_1-C₄ alcohols, b) Isolating the Alfuzosin hydrochloride by adding suitable solvents selected from ethylacetate, methylacetate, isopropyl acetate, methyl isopropyl acetate, toluene, cyclohexane and n-heptane and hexanes, c) Slurrying the above obtained wet Alfuzosin hydrochloride in an anti-solvents like ethylacetate, methylacetate, isopropyl acetate, methyl isopropyl acetate, toluene, cyclohexane and n-heptane, d) Separating the solid by filtration and drying the material to get the non-solvated crystalline form of Alfuzosin hydrochloride compound of formula- 1.

The third aspect of the invention is to provide an isopropyl alcohol solvated form of Alfuzosin hydrochloride and process for preparing the same, the process comprises of the following steps a) Reacting the Alfuzosin compound of formula-7 with suitable alcoholic hydrochloric acid selected from methanolic hydrochloric acid, isopropanolic hydrochloric acid or ester hydrochloric acid such as ethyl acetate hydrochloric acid preferably isopropanolic hydrochloric acid in a suitable organic solvents selected from C_1-C₄ alcohols, b) Isolating the isopropyl alcohol solvated form by adding the suitable anti-solvent selected from methanol, ethanol, isopropanol and/or acetone, c) Separating the solid by filtration and drying the material to get the isopropyl alcohol solvated form of Alfuzosin hydrochloride compound of formula- 1.

The fourth aspect of the present invention is to provide an amorphous form of Alfuzosin hydrochloride and process for the preparing the same, the process comprises of the following steps a) Adding alcoholic hydrochloride such as methanolic hydrochloride to a mixture of Alfuzosin base compound of formula-7 in a suitable organic solvent such as methanol, b) Removing the solvent completely under reduced pressure to get the Amorphous form of Alfuzosin hydrochloride compound of formula- 1.

Non-solvated crystalline form of Alfuzosin hydrochloride, Amorphous form and solvated forms can be distinguished from each other by means of XRD, IR spectra, RS/OVI and thermal analysis.

IR analysis is carried out on Thermo Nicolet-380 model, Thermal analysis is carried out on Waters DSC Q-IO model and RS/OVI analysis carried out on Shimadzu GC-2010 with AOC 5000 (Auto sampler) with Flame Ionization detector.

Related substances by HPLC of Alfuzosin hydrochloride is carried out using a liquid chromatograph is equipped with variable wavelength UV-Detector and integrator, Inertsil ODS-2, 150x4.6 mm, 5μm or equivalent column, 1.5 ml/min flow rate at 254 nm, ambient temperature, and the buffer is used 5 ml of perchloricacid in 900 ml water, pH is adjusted to 3.5 with dilute sodium hydroxide and dilute to 1000 ml with water. Mobile phase (Buffer: Acetonitrile: THF; 800:200:10)

XRD analysis of Alfuzosin hydrochloride is carried out using SIEMENS/D-5000 X-Ray Diffractometer using Cu, Ka radiation of wavelength 1.54 A° and continuous scan speed of 0.0457min. The present invention is schematically represented as follows

Methanol Sulphuricacid

Formula-2 Formula-3

Formula-6 Formula-5 Isoamylalcohol

Formula-7

Alcoholic HCl/IPA/Ethylacetate

Formula- 1 The process described in the present invention was demonstrated in examples illustrated below. These examples are provided as an illustration only and therefore should not be construed as limitation of the scope of the invention.

Example-1:

Preparation of Nl-Methyl-N2-(tetrahyrofuroyl-2-)-propylene diamine compound of formula-5

Added 1.68 liters of sulphuric acid to a mixture of 35 Kgs. of 2-tetrahydrofuroic acid and 350 liters of methanol at 25-35°C. Stirred the reaction mixture for 5 hours at 25-35°C. Added 29.47 Kgs. of methyl amino propyl amine slowly to the above reaction mixture at 25-35°C. Heated the reaction mixture to 40-45⁰C. Stirred the reaction mixture for 40 hours at 40-45⁰C. Distilled the solvent completely under reduced pressure at below 65⁰C. Cooled the reaction mixture to 25-35°C. Added 175 liters of isopropyl alcohol to the above reaction mixture at 25-35°C. Stirred the reaction mixture for 40 minutes at 25 -35⁰C. Filtered the inorganic solids and washed with isopropyl alcohol. Distilled the filtrate under reduced pressure at below 75°C. Cooled the residue to 25-35°C to get the title compound. Yield: 54.4 Kgs.

Example-2:

Preparation of Ni-(4-amino-6,7-dimethoxyquinazol-2-yl)-Ni-methyl-N2-

(tetrahydrofuroyl-2)-propylenediamine compound of formula-7

Heated a suspension of 38.4 Kgs. of 4-amino-2-chloro-6,7-dimethoxyquinazoline and 20 Kgs. of Nl-methyl-N2-tetrahydrofuroyl propylene diamine in 53 liters of isoamylalcohol to reflux temperature of 125-135⁰C. Stirred the reaction mixture for 14 hours at reflux temperature. Distilled the solvent completely under reduced pressure at below 120°C. Cooled the reaction mixture to 40-50⁰C. Added 70 liters of acetone to the above reaction mixture and distilled the solvent completely under reduced pressure at below 55°C. Cooled the reaction mixture to 40-50⁰C. Added 176 liters of acetone to the above reaction mixture at 40-50⁰C. Further cooled the reaction mixture to 25-35°C. Stirred the reaction mixture for 60 minutes and filtered the solid. Added 350 liters of water to the above obtained wet material and treated with activated carbon. Added 140 liters of acetone to the filtrate. Cooled the reaction mixture to 10-15⁰C. Adjusted the pH of the reaction mixture to 13.6 with 20% sodium hydroxide solution at 10-15°C. Stirred the reaction mixture for 10 hours at 10-15°C. Filtered the obtained solid and washed with a mixture of water and acetone. Added 176 liters of ethyl acetate to the above obtained wet solid. Heated the reaction mixture to reflux temperature of 60-65°C. Stirred the reaction mixture at reflux for 60 minutes. Cooled the reaction mixture to 0-5°C. Stirred the reaction mixture for 90 minutes. Filtered the solid and washed with ethyl acetate. Dried the material at 70-80°C to get the title compound. Yield: 29.9 Kgs. HPLC purity: 99.99%

Example-3:

Purification of Alfuzosin compound of formula-7

Heated a mixture of 40 Kgs. of Alfuzosin compound of formula-7 and 250 liters of methylenechloride to reflux temperature of 60-65°C. Stirred the reaction mixture for 60 minutes at reflux. Cooled the reaction mixture to 0-5⁰C. Stirred the reaction mixture for 90 minutes at 0-5⁰C. Filtered the solid and washed with methylenechloride. Dried the material at 70-80°C to get the title compound. Yield: 28 Kgs. HPLC purity: 99.99%

Example-4:

Purification of Alfuzosin compound of formula-7

Heated a mixture of 40 Kgs. of Alfuzosin compound of formula-7 and 250 liters of acetonitrile to reflux temperature of 60-65°C. Stirred the reaction mixture for 60 minutes at reflux. Cooled the reaction mixture to 0-5⁰C. Stirred the reaction mixture for 90 minutes at 0-5⁰C. Filtered the solid and washed with acetonitrile. Dried the material at 70-80°C to get the title compound. Yield: 28 Kgs. HPLC purity: 99.99% Example-5:

Purification of Alfuzosin compound of formula-7

Heated a mixture of 40 Kgs. of Alfuzosin compound of formula-7 and 250 liters of ethyl acetate to reflux temperature of 60-65°C. Stirred the reaction mixture for 60 minutes at reflux. Cooled the reaction mixture to 0-5 °C. Stirred the reaction mixture for 90 minutes at 0-5°C. Filtered the solid and washed with ethyl acetate. Dried the material at 70-80°C to get the title compound. Yield: 31 Kgs. HPLC purity: 99.99%

Example-6:

Preparation of Alfuzosin hydrochloride compound of formula- 1

Heated a suspension of 13 Kgs. of N₁-(4-amino-6,7-dimethoxyquinazol-2-yl)-N₁- methyl-N₂-(tetrahydrofuroyl-2)-propylenediamine and 65 liters of methanol to 50-55°C. Adjusted the pH of the reaction mixture below 2 with methanolic hydrochloric acid. Added the above reaction mixture slowly to the 175 liters of ethyl acetate at 25-35⁰C. Stirred the reaction mixture for 60 minutes at 25-35°C. Filtered the obtained solid and washed with ethyl acetate. Added 195 liters of ethyl acetate to the above obtained wet material. Heated the reaction mixture to reflux. Stirred the reaction mixture for 30 minutes at reflux. Cooled the reaction mixture to 25-35⁰C. Stirred the reaction mixture for 60 minutes at 25-35°C. Filtered the solid and washed with ethyl acetate. Dried the material at 95-105⁰C for 8 hours to get the title compound. Yield: 12.5 Kgs. HPLC: 99.96% Moisture content: 0.6% (w/w)

Example-7:

Preparation of Non-solvated crystalline form of Alfuzosin hydrochloride compound of formula-1

Heated a suspension of 13 Kgs. of N₁-(4-amino-6,7-dimethoxyquinazol-2-yl)-N₁- methyl-N₂-(tetraliydrofuroyl-2)-propylenediamine and 65 liters of methanol to 50-55⁰C. Adjusted the pH of the reaction mixture to below 2 with methanolic hydrochloric acid. Added the above reaction mixture slowly to the 175 liters of ethyl acetate at 25-35⁰C. Stirred the reaction mixture for 60 minutes at 25 -35⁰C. Filtered the obtained solid and washed with ethyl acetate. Added 195 liters of ethyl acetate to the above obtained wet material. Heated the reaction mixture to reflux. Stirred the reaction mixture for 30 minutes at reflux. Cooled the reaction mixture to 25-35°C. Stirred the reaction mixture for 60 minutes at 25-35°C. Filtered the solid and washed with ethyl acetate. Added 195 liters of ethyl acetate to the above obtained wet material. Heated the reaction mixture to reflux. Stirred the reaction mixture for 30 minutes at reflux. Cooled the reaction mixture to 25-35°C. Filtered the solid and washed with ethyl acetate. Dried the material at 95-105⁰C for 8 hours to get the title compound. Yield: 12.2 Kgs. HPLC purity: 99.98% Moisture content: 0.5 %(w/w)

Example-8:

Preparation of Isopropyl alcohol solvated form of Alfuzosin hydrochloride compound of formula-1

Added 10 ml of methanolic hydrochloride to a suspension of 10 grams of N₁-(4-amino-6,7-dimethoxyquinazol-2-yl)-N₁-methyl-N₂-(tetrahydrofuroyl-2)- propylenediamine in 30 ml of methanol. Cooled the reaction mixture to 10-15⁰C. Added 100 ml of isopropyl alcohol to the above reaction mixture. Stirred the reaction mixture for 2 hours at 10-15⁰C. Filtered the solid and washed with isopropyl alcohol. Dried the solid at 100⁰C for 15 hours to get isopropyl alcohol solvated form of Alfuzosin hydrochloride. Yield: 10 grams Example-9:

Adjusted the pH of the suspension of 10 grams of Alfuzosin base compound of formula-7 in 100 ml of acetone to 2 with isopropanolic hydrochloride. Stirred the reaction mixture for 20 minutes. Filtered the solid. Dried the solid at 100°C under reduced pressure to get isopropyl alcohol solvated form of Alfuzosin hydrochloride. Yield: 10 grams

Example-10:

Preparation of Amorphous Alfuzosin hydrochloride compound of formula-1

Added 10 ml of methanolic hydrochloride to a mixture of 10 grams of Alfuzosin compound of formula-7 in 30 ml of methanol. Removing the solvent under reduced pressure in buchi roto vapour. Dried the solid at 125⁰C for 2 hours under reduced pressure to get the Amorphous Alfuzosin hydrochloride. Yield: 10.5 grams

Claims

We Claim:

1. An improved and industrial process for the preparation of Alfuzosin hydrochloride compound of formula- 1

Formula- 1

Which comprises of the following steps, a) Reacting an acid compound of formula-2

Formula-2 with suitable alcohol such as methanol in presence of a suitable acid catalyst such as sulphuric acid to give ester compound of formula-3

Formula-3 which in-situ reacting with diamine compound of formula-4

N H T H

Formula-4 in a suitable alcoholic solvent like methanol to give amide compound of formula-5,

Formula-7 c) Purifying the compound of formula-7 by using alcoholic solvents like methanol, ethanol, isopropyl alcohol and propanol and/or keto solvents like acetone, methylisobutylketone, methylethylketone and/or nitrile solvents like acetonitrile and/or ester solvents like ethyl acetate, methyl acetate, isopropyl acetate and methyl isopropyl acetate and/or chloro solvents like methylene chloride and chloroform preferably chloro solvents and ester solvents, most preferably ester solvents such as ethyl acetate, d) Reacting the compound of formula-7 with suitable alcoholic hydrochloric acid selected from methanolic hydrochloric acid, isopropanolic hydrochloric acid or ester hydrochloric acid such as ethyl acetate hydrochloric acid preferably methanolic hydrochloric acid in a suitable organic solvents selected from C_1-C₄ alcohols and isolating the Alfuzosin hydrochloride compound of formula- 1 by adding the reaction mixture to suitable anti-solvents selected from the solvents like ethylacetate, methylacetate, isopropyl acetate, methyl isopropyl acetate, toluene, cyclohexane and n-heptane at the temperature from 0°C to reflux temperature of the solvent used.

2. The process according to claim 1 a), wherein the solvent used is methanol at a temperature ranges from 0°C to reflux temperature of the solvent preferably at 25-35°C.

3. The process according to claim 1 a), wherein the esterification of compound of formula-2 with methanol in the presence of suitable acid catalyst such as sulfuric acid, thionyl chloride, preferably sulfuric acid used in the range of 0.05 moles to 0.5 moles preferably 0.1 moles.

4. The process according to claim 1 a), wherein the in-situ condensation of compound of formula-3 with compound of formula-4 in presence of C₁-C₃ alcohols preferably methanol at a temperature ranges of 0°C to reflux temperature of solvent used preferably at 40-45⁰C.

5. The process according to claim 1 b), where in the solvent used is selected from the C₁-C₅ alcohols, sulfolane, toluene, acetone, Xylene and dimethyl formamide preferably isoamylalcohol at a temperature of about 100°C to reflux temperature of the solvent used, preferably at about 125-135°C.

6. The process according to claim 1 c), wherein the solvent used for purification is Acetonitrile.

7. The process according to claim 1 c), wherein the solvent used for purification is Methylenechloride.

8. The process according to claim 1 c), wherein the solvent used for purification is Ethyl acetate.

9. An improved and industrial process for the preparation of Non-solvated crystalline form of Alfuzosin hydrochloride compound of formula- 1 , which comprises of the following steps a) Reacting the Alfuzosin compound of formula-7 with suitable alcoholic hydrochloric acid selected from methanolic hydrochloric acid, isopropanolic hydrochloric acid or ester hydrochloric acid such as ethyl acetate hydrochloric acid preferably methanolic hydrochloric acid in a suitable organic solvents selected from C₁-C₄ alcohols, b) Isolating the Alfuzosin hydrochloride by adding suitable solvents selected from ethylacetate, methylacetate, isopropyl acetate, methyl isopropyl acetate, toluene, cyclohexane and n-heptane and hexanes, c) Slurrying the above obtained wet Alfuzosin hydrochloride in an anti-solvents like ethylacetate, methylacetate, isopropyl acetate, methyl isopropyl acetate, toluene, cyclohexane and n-heptane, d) Separating the solid by filtration and drying the material to get the Non-solvated crystalline form of Alfuzosin hydrochloride compound of formula- 1.

10. A process according to claim 9 b) and 9 c) wherein the solvent is ethyl acetate for isolation and slurry.

11. Isopropyl alcohol solvated form of Alfuzosin hydrochloride which is characterized by GC chromatogram (i.e., RS/OVI) shown in Figure-6.

12. A process for the preparation of isopropyl alcohol solvated form of Alfuzosin hydrochloride compound of formula- 1, which comprises of the following steps a) Reacting the Alfuzosin compound of formula-7 with suitable alcoholic hydrochloric acid selected from methanolic hydrochloric acid, isopropanolic hydrochloric acid or ester hydrochloric acid such as ethyl acetate hydrochloric acid preferably isopropanolic hydrochloric acid in a suitable organic solvents selected from C_1-C₄ alcohols, b) Isolating the isopropyl alcohol solvated form by adding the suitable anti-solvent selected from methanol, ethanol, isopropanol and acetone, c) Separating the solid by filtration and drying the material to get the isopropyl alcohol solvated form of Alfuzosin hydrochloride compound of formula- 1.

13. An amorphous form of Alfuzosin hydrochloride.

14. Amorphous form of Alfuzosin hydrochloride according to claim 13 is characterized by the XRD shown in figure-5.

15. A process for the preparation of amorphous form of Alfuzosin hydrochloride compound of formula- 1, which comprises of the following steps a) Adding alcoholic hydrochloride such as methanolic hydrochloride to a mixture of Alfuzosin base compound of formula-7 in a suitable organic solvent such as methanol, b) Removing the solvent completely under reduced pressure to get the amorphous Alfuzosin hydrochloride compound of formula- 1.