Trazodone and trazodone hydrochloride in purified form

Abstract

A process of production of trazodone or trazodone hydrochloride that comprises: (a) preparing an organic phase comprising trazodone in at least one organic solvent; (b) preparing an aqueous phase comprising at least one basic compound; (c) mixing said aqueous phase with said organic phase; (d) heating at a temperature of at least 40° C. for at least 30 minutes; (e) recovering said trazodone; and, optionally, (f) treating said trazodone with hydrochloric acid to obtain trazodone hydrochloride. Trazodone or trazodone hydrochloride comprising less than 15 ppm of alkylating substances, and a pharmaceutical composition comprising said trazodone hydrochloride.

1 - 28 . (canceled) 
     
     
         29 . A pharmaceutical composition, comprising trazodone hydrochloride and at least one pharmaceutically acceptable excipient, wherein said trazodone hydrochloride comprises less than 15 ppm of alkylating substances. 
     
     
         30 . A pharmaceutical composition according to  claim 29 , wherein said trazodone hydrochloride comprises less than 10 ppm of alkylating substances. 
     
     
         31 . A pharmaceutical composition according to  claim 29 , wherein said trazodone hydrochloride comprises less than 2.5 ppm of alkylating substances. 
     
     
         32 . A pharmaceutical composition according to  claim 29 , wherein said at least one pharmaceutically acceptable excipient is selected from the group consisting of antiadherents, binders, disintegrants, fillers, diluents, flavouring agents, colorants, fluidizers, lubricants, preservatives, moistening agents, absorbents, and sweeteners. 
     
     
         33 . A pharmaceutical composition according to  claim 29 , wherein said at least one pharmaceutically acceptable excipient is a sugar. 
     
     
         34 . A pharmaceutical composition according to  claim 33 , wherein said sugar is selected from the group consisting of lactose, glucose and sucrose. 
     
     
         35 . A pharmaceutical composition according to  claim 29 , wherein said at least one pharmaceutically acceptable excipient is a starch. 
     
     
         36 . A pharmaceutical composition according to  claim 35 , wherein said starch is selected from the group consisting of maize starch and potato starch. 
     
     
         37 . A pharmaceutical composition according to  claim 29 , wherein said at least one pharmaceutically acceptable excipient is cellulose or a derivative thereof. 
     
     
         38 . A pharmaceutical composition according to  claim 37 , wherein said cellulose or a derivative thereof is selected from the group consisting of sodium carboxymethylcellulose, ethylcellulose and cellulose acetate. 
     
     
         39 . A pharmaceutical composition according to  claim 29 , wherein said at least one pharmaceutically acceptable excipient is a glycol or a polyol. 
     
     
         40 . A pharmaceutical composition according to  claim 39 , wherein said glycol or polyol is selected from the group consisting of propylene glycols, glycerol, sorbitol, mannitol, and polyethylene glycol. 
     
     
         41 . A pharmaceutical composition according to  claim 29 , wherein said at least one pharmaceutically acceptable excipient is an ester. 
     
     
         42 . A pharmaceutical 1 composition according to  claim 41 , wherein said ester is selected from the group consisting of ethyl oleate and ethyl laurate. 
     
     
         43 . A pharmaceutical composition according to  claim 29 , wherein said at least one pharmaceutically acceptable excipient is an oil. 
     
     
         44 . A pharmaceutical composition according to  claim 43 , wherein said oil is selected from the group consisting of peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, maize oil, and soya oil. 
     
     
         45 . A pharmaceutical composition according to  claim 29 , wherein said at least one pharmaceutically acceptable excipient is selected from the group consisting of gum tragacanth, malt, gelatin, talc, cocoa butter, waxes, agar-agar, magnesium hydroxide, aluminium hydroxide, alginic acid, water, isotonic solutions, ethanol, buffer solutions, polyesters, polycarbonates, and polyanhydrides. 
     
     
         46 . A pharmaceutical composition according to  claim 29 , wherein said composition is for oral or parenteral administration. 
     
     
         47 . A pharmaceutical composition according to  claim 46 , wherein said composition for oral or parenteral administration is in the form of tablets, lozenges, capsules, solutions, suspensions, dispersions, and syrups. 
     
     
         48 . A pharmaceutical composition according to  claim 29 , wherein said alkylating substances are selected from the group consisting of 2,2-dichloroethylamine, 1-bromo-3-chloro-propane, N-(3-chlorophenyl)-N′-(3-chloropropyl)-piperazine, 2-(3-chloropropyl)-s-triazolo-[4,3-a]-pyridin-3-one, 3-chloro-N,N′-dichloro-ethyl-aniline, 2-{3-[bis-(2-chloroethyl)-amino]-propyl}-2H-[1,2,4]triaz-olo[4,3-a]pyridin-3-one, 2,2-dibromoethylamine, and 1,3-dichloro-propane. 
     
     
         49 . A pharmaceutical composition according to  claim 29 , wherein said trazodone hydrochloride comprises less than 1 ppm of each of said alkylating substances. 
     
     
         50 . A pharmaceutical composition according to  claim 49 , wherein said alkylating substances are selected from the group consisting of 2,2-dichloroethylamine, 1-bromo-3-chloropropane, N-(3-chlorophenyl)-N′-(3-chloropropyl)-piperazine, 2-(3-chloropropyl)-s-triazolo-[4,3-a]-pyridin-3-one, 3-chloro-N,N′-dichloroethylaniline, 2-{3-[bis-(2-chloroethyl)-amino]-propyl}-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one, 2,2-dibromoethylamine, and 1,3-dichloropropane. 
     
     
         51 . A pharmaceutical composition according to  claim 49 , wherein said alkylating substances are selected from the group consisting of 2,2-dichloroethylamine, 1-bromo-3-chloro-propane, and N-(3-chlorophenyl)-N-(3-chloropropyl)-piperazine.