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Novel polymorphs of efavirenzRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Heterocyclic Carbon Compounds Containing A Hetero Ring Having Chalcogen (i.e., O,s,se Or Te) Or Nitrogen As The Only Ring Hetero Atoms Doai, Hetero Ring Is Six-membered And Includes At Least Nitrogen And Oxygen As Ring Hetero Atoms (e.g., Monocyclic 1,2- And 1,3-oxazines, Etc.), Polycyclo Ring System Having The Six-membered Hetero Ring As One Of The Cyclos (e.g., Maytansinoids, Etc.), Bicyclo Ring System Having The Six-membered Hetero Ring As One Of The Cyclos (e.g., 1,4-benzoxazines, Etc.)Novel polymorphs of efavirenz description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20060235008, Novel polymorphs of efavirenz. Brief Patent Description - Full Patent Description - Patent Application Claims
FIELD OF THE INVENTION [0001] The present invention relates to novel polymorphs of efavirenz, processes for their preparation and pharmaceutical compositions containing them. BACKGROUND OF THE INVENTION [0002] The present invention relates to novel polymorphs of efavirenz, processes for their preparation and pharmaceutical compositions containing them. [0003] Pharmaceutical products with HIV reverse transcriptase (including its resistant varieties) inhibitors are described in U.S. Pat. No. 5,519,021. An especially important compound among those disclosed is efavirenz, (4S)-6-chloro-4-(cyclopropylethyny])-1,4-dihydro-4-(trifluoromethyl)-2H-3- ,1-ben.SIGMA.oxazin-2-one. Efavirenz has the following structural formula: [0004] This compound is used for the preparation of a medicament having nonnucleoside HIV-1 reverse transcriptase inhibiting activity that is useful in the prevention or treatment of infection by HIV and the treatment of AIDS. Efavirenz is sold commercially as SUSTIVA.RTM. by Bristol Myers Squibb. [0005] WO patent application publication No. 98/33782 disclosed three crystalline forms, Form I (characterized by an x-ray powder diffraction patterns having peaks expressed as 2.THETA. at 6.1, 6.4, 10.4, 10.9, 12.3, 13.2, 14.2, 15.2, 16.9, 18.4, 19.2, 20.1, 21.2, 22.3, 23.0, 24.9, 25.9, 26.3, 27.2, 28.1, 28.6, 29.1, 29.5, 30.7, 32.4 and 38.3 degrees), Form II (characterized by an x-ray powder diffraction patterns having peaks expressed as 2.THETA. at 3.6, 6.3, 11.1, 12.8, 13.3, 14.3, 16.1, 16.9, 18.5, 19.2, 19.6, 20.6, 21.3, 22.6, 23.2, 24.4, 24.9, 26.0, 26.8, 27.6, 28.4, 29.2, 29.6, 30.6, 31.9 and 33.8 degrees) and Form III (characterized by an x-ray powder diffraction patterns having peaks expressed as 2.THETA. at 7.2, 10.9, 13.7, 14.5, 16.7, 19.1, 19.6, 20.8, 21.7, 22.3, 22.8, 23.2, 23.9, 24.5, 24.9, 25.8, 27.0, 27.6, 29.3, 30.3, 30.7, 31.3, 33.4, 38.4 and 39.2 degrees) of efaviren .SIGMA.. [0006] WO patent application publication No. 99/64405 disclosed fivs crystalline forms, Form 1 (characterized by an x-ray powder diffraction patterns having peaks expressed as 26 at about 6.0, 6.3, 10.3, 10.8, 14.1, 16.8, 20.0, 20.5, 21.1 and 24.8 degrees), Form 2 (characterized by an x-ray powder diffraction patterns having peaks expressed as 26 at about 6.8, 9.2, 12.3, 16.2, 21.4, 22.7, 24.1 and 28.0 degrees), Form 3 (characterized by an x-ray powder diffraction patterns having peaks expressed as 26 at about 7.1, 7.3, 11.0, 13.8, 20.9, 23.3, 27.9 and 33.5 degrees), Form 4 (characterized by an x-ray powder diffraction patterns having peaks expressed as 26 at about 3.6, 6.3, 9.7, 11.0, 12.7, 13.2, 16.1, 19.2, 19.5/20.6 and 24.3 degrees) and Form 5 (characterized by an x-ray powder diffraction patterns having peaks expressed as 26 at about 10.2, 11.4, 11.6, 12.6, 19.1, 20.6, 21.3, 22.8, 24.8, 27.4, 28.2 and 31.6 degrees) of efaviren .SIGMA.. [0007] We have discovered a stable novel crystalline form of efavirenz. The novel form is at least as stable as the reported forms (Form I, Form II, Form III, Form 1, Form 2, Form 3, Form 4 and Form 5). The novel crystalline form is stable over the time and has good flow properties and so, the novel crystalline form is suitable for formulating efavirenz. [0008] Amorphous form of efavirenz has not been reported in the prior art. So, there is a need for stable amorphous form of efavirenz for better pharmaceutical preparations. [0009] One object of the present invention is to provide a stable novel crystalline form of efavirenz, process for preparing it and a pharmaceutical composition containing it. [0010] Another object of the present invention is to provide a novel stable amorphous form of efavirenz, process for preparing it and a pharmaceutical composition containing it. DETAILED DESCRIPTION OF THE INVENTION [0011] In accordance with the present invention, there is provided a novel amorphous form of efavirenz. The amorphous efavirenz is characterized by having broad x-ray diffraction spectrum as in FIG. 1. [0012] In accordance with the present invention, a process is provided for preparation of amorphous efavirenz, which comprises: [0013] a) precipitating from a solution of efavirenz in a C.sub.3-C.sub.8-ketonic solvent by using water as precipitating solvent at below about 15.degree. C., and collecting the precipitated solid; and [0014] b) drying the solid collected at about 40.degree. C.-65.degree. C. to obtain amorphous efavirenz. [0015] The preferable ketonic solvent is selected from acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl tert-butyl ketone and diethyl ketone; more preferable ketonic solvent is selected from acetone and diethyl ketone; and still more preferable ketonic solvent is acetone. [0016] The solution of efavirenz in the ketonic solvent may be prepared by dissolving efavirenz in a known form or in crystalline form H1 described below in ths said ketonic solvent. Alternatively, crude efavirenz may also be used in the process. [0017] Preferably the precipitation is carried out at about 0.degree. C.-10.degree. C. and more preferably at about 2.degree. C.-5.degree. C. [0018] The precipitated solid may be collected by filtration or centrifugation. [0019] The preferable temperature range of drying is at about 50.degree. C.-60.degree. C. and more preferable temperature range is at about 55.degree. C.-60.degree. C. [0020] Preferably the process is carried out by precipitating from a solution of efavirenz in a C.sub.3-C.sub.8-ketonic solvent, preferably acetone, by adding the said solution to water at about 0.degree. C.-10.degree. C. and more preferably at about 2.degree. C.-5.degree. C.; collecting the precipitated solid by filtration or centrifugation; and drying the solid collected at about 40.degree. C.-65.degree. C., more preferably at about 55.degree. C.-60.degree. C. to obtain amorphous efavirenz. [0021] The novel amorphous efavirenz is found to have better dissolution properties when compared with the known forms. [0022] In accordance with the present invention, there is provided a novel crystalline form of efavirenz, designated as form H1, characterized by an x-ray powder diffraction spectrum having peaks expressed as 2.THETA. at about 5.4, 10.4, 11.6, 12.5, 15.3, 20.1, 20.8, 22.5, 23.1, 25.7, 27.9, 28.5, 28.8, 29.5, 30.2 and 38.2 degrees. FIG. 2 shows typical form H1 x-ray powder diffraction spectrum. [0023] In accordance with the present invention, a process is provided for preparation of efavirenz form H1, which comprises: [0024] si) precipitating from a solution of efavirenz in a c-, -c.sub.0-alcoholic, Cs-Gs-ketonic solvent or a mixture thereof by using water as precipitating solvent at below about 15.degree. C., collecting the precipitated solid; [0025] b) drying the solid collected at about 25.degree. C.-35.degree. C. until the water content falls in the range 2-10% of the solid by weight; and [0026] c) drying the solid obtained in (b) at about 40.degree. C.-55.degree. C. to obtain crystalline efavirenz form H1. Continue reading about Novel polymorphs of efavirenz... Full patent description for Novel polymorphs of efavirenz Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Novel polymorphs of efavirenz patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. 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