Sertraline hydrochloride polymorphs

Details Sertraline hydrochloride polymorphs Sertraline hydrochloride polymorphs

1999-11-24

2002-12-31

Barts, Samuel (Department: 1609)

Organic compounds -- part of the class 532-570 series

Organic compounds

Amino nitrogen containing

C514S647000

Reexamination Certificate

active

06500987

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to novel crystalline forms of sertraline hydrochloride, (1S-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl- 1-naphthalenaminehydrochloride, denominated Forms VI through X, an amorphous form and novel, reproducible methods for preparing them and for preparing previously reported polymorphs II, III and V.
BACKGROUND OF THE INVENTION
Sertraline hydrochloride, (1S-cis)4-(3,4 dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine hydrochloride, having the formula
is approved, under the trademark Zoloft®, by the U.S. Food and Drug Administration, for the treatment of depression, obsessive-compulsive disorder and panic disorder.
U.S. Pat. No. 4,536,518 describes a synthesis of sertraline hydrochloride. U.S. Pat. No. 5,248,699 describes five crystalline forms of sertraline hydrochloride, designated Form I, Form II, Form III, Form IV and Form V.
U.S. Pat. No. 4,536,518 (“the '518 patent”) describes the preparation of sertraline hydrochloride with a melting point of 243-245° C. by treating an ethyl acetate/ether solution of the free base with gaseous hydrogen chloride. The solid state properties of the sertraline hydrochloride so produced are not otherwise disclosed.
According to U.S. Pat. No. 5,248,699 (“the '699 patent”), the sertraline hydrochloride produced by the method of the '518 patent has a crystalline form denominated “Form II”. The '699 patent discloses four other polymorphs I, III, IV, and V, and characterizes them by single crystal x-ray analysis, powder x-ray diffraction, infra-red spectroscopy, and differential scanning calorimetry. The '699 patent reports that Form II is produced by rapid crystallization of sertraline hydrochloride from an organic solvent, including isopropyl alcohol, hexane, generally describes methods for making sertraline hydrochloride Forms I-V. According to this patent, the preferential formation of Forms I, II or IV in an acidic solution consisting of isopropyl alcohol, hexane, and acetone, methyl isobutyl ketone, glacial acetic acid, or preferably, ethyl acetate depends on the rapidity of crystallization. Form I is described as being made by crystallizing sertraline hydrochloride in an acidic solution using an organic solvent such as those listed above. The crystallization of Form I is carried out at a temperature from about 20° C. to about the solvent reflux temperature, preferably from about 40° to 60° C. The only method described in this patent for making Forms II and IV is by the rapid crystallization of sertraline hydrochloride from an organic solvent such as those listed above. Slow crystallization or granulation of sertraline hydrochloride will produce Form I. Form III is described as being formed by heating Forms I, II or IV to temperatures above about 180° C. Granulating either of Forms II, III or IV in isopropyl alcohol, ethyl acetate, hexane or any of the solvents listed above at a temperature from about 40° to 60° C. causes conversion to Form I. The only method described in this patent for making Form V is by sublimation of sertraline hydrochloride Form I at reduced pressure and at a temperature from about 180-190° C. onto a condenser. However, in our hands attempts to repeat this procedure to obtain Form V have been unsuccessful.
SUMMARY OF THE INVENTION
It has now been discovered that sertraline hydrochloride Form V can be formed by crystallization from various solvents rather than by sublimation. The existence of new crystal forms of sertraline hydrochloride, denominated Forms VI, VII, VIII, IX and X, and an amorphous of sertraline hydrochloride have been discovered. Form VI is a useful intermediate in the formation of previously reported sertraline hydrochloride Forms I, II and V.
The present invention also relates to sertraline hydrochloride ethanolate and processes for making sertraline hydrochloride ethanolate.
The present invention also relates to sertraline hydrochloride methanolate and processes for making sertraline hydrochloride methanolate.
The present invention also relates to sertraline hydrochloride solvate and processes for making sertraline hydrochloride solvate.


REFERENCES:
patent: 4536518 (1985-08-01), Welch, Jr. et al.
patent: 5082970 (1992-01-01), Braish
patent: 5248699 (1993-09-01), Sysko et al.
patent: 5463126 (1995-10-01), Williams
patent: 5734083 (1998-03-01), Wilson et al.
patent: 2000-26378 (2000-01-01), None
patent: 2000-26379 (2000-01-01), None
patent: WO 01/90049 (2001-11-01), None

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