Composition of a 5-ht2a serotonin receptor modulator useful for the treatment of disorders related thereto

Abstract

The present invention relates to certain compositions of a 5-HT 2A serotonin receptor modulator and methods for their preparation. The compositions disclosed herein are useful for increasing slow wave sleep, improving sleep consolidation, improving sleep maintenance and improving sleep quality, and for treating insomnia and related sleep disorders, dyssomnias, parasomnias and nonrestorative sleep and the like. The compositions disclosed herein are further useful for treating platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, thrombosis, asthma or symptoms thereof, agitation or symptoms thereof, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorders, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, diabetic-related disorders and progressive multifocal leukoencephalopathy and the like.

1 .- 50 . (canceled) 
     
     
         51 . A method for preparing a pharmaceutical composition comprising:
 a. 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea; and   b. an excipient selected from: PVP and coPVP;   wherein the method comprises blending said 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea and said excipient in a blender.   
     
     
         52 . The method for preparing a pharmaceutical composition according to  claim 51 , wherein the pharmaceutical composition further comprises:
 c. methyl cellulose;   wherein the method comprises blending said 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea, said excipient and said methyl cellulose in a blender.   
     
     
         53 . The method for preparing a pharmaceutical composition according to  claim 51 , wherein the 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea is Form I of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea. 
     
     
         54 . The method for preparing a pharmaceutical composition according to  claim 52 , wherein the methyl cellulose is 4000 cps methyl cellulose. 
     
     
         55 . The method for preparing a pharmaceutical composition according to  claim 51 , wherein, the excipient is PVP. 
     
     
         56 . The method for preparing a pharmaceutical composition according to  claim 55 , wherein, the PVP is Plasdone™ K-29/32 PVP or Kollidon™ 30 PVP 
     
     
         57 . The method for preparing a pharmaceutical composition according to  claim 51 , wherein, the excipient is coPVP. 
     
     
         58 . The method for preparing a pharmaceutical composition according to  claim 57 , wherein, the coPVP is Kollidon™ VA 64 PVP. 
     
     
         59 . The method for preparing a pharmaceutical composition according to  claim 53 , wherein said method comprises:
 a. blending Form I of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea, PVP, methyl cellulose, lactose monohydrate, microcrystalline cellulose, crospovidone, sodium lauryl sulfate and silicon dioxide to produce a first blend;   b. delumping said first blend in a conical mill; and   c. blending said first blend with magnesium stearate.   
     
     
         60 . The method for preparing a pharmaceutical composition according to  claim 53 , wherein said pharmaceutical composition comprises:
 a. Form I of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea in an amount of about 0.01% to about 5% by weight of the total composition;   b. Plasdone™ K-29/32 PVP or Kollidon™ 30 PVP in an amount of about 40% by weight of the total composition;   c. methyl cellulose in an amount of about 2% by weight of the total composition;   d. lactose monohydrate, 316 in an amount of about 21.25% by weight of the total composition;   e. microcrystalline cellulose, PH-102 in an amount of about 25% by weight of the total composition;   f. Kollidon™ CL in an amount of about 4% by weight of the total composition;   g. sodium lauryl sulfate in an amount of about 2% by weight of the total composition;   h. magnesium stearate in an amount of about 0.5% by weight of the total composition; and   i. silicon dioxide in an amount of about 0.25% by weight of the total composition.   
     
     
         61 . The method for preparing a pharmaceutical composition according to  claim 53 , wherein said method comprises:
 a. blending Form I of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea, coPVP, methyl cellulose, lactose monohydrate, microcrystalline cellulose, crospovidone, sodium lauryl sulfate and silicon dioxide to produce a first blend;   b. delumping said first blend in a conical mill; and   c. blending said first blend with magnesium stearate.   
     
     
         62 . The method for preparing a pharmaceutical composition according to  claim 53 , wherein said pharmaceutical composition comprises:
 a. Form I of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea in an amount of about 0.01% to about 5% by weight of the total composition;   b. Kollidon™ VA 64 coPVP in an amount of about 40% by weight of the total composition;   c. methyl cellulose in an amount of about 2% by weight of the total composition;   d. lactose monohydrate, 316 in an amount of about 21.25% by weight of the total composition;   e. microcrystalline cellulose, PH-102 in an amount of about 25% by weight of the total composition;   f Kollidon™ CL in an amount of about 4% by weight of the total composition;   g. sodium lauryl sulfate in an amount of about 2% by weight of the total composition;   h. magnesium stearate in an amount of about 0.5% by weight of the total composition; and   i. silicon dioxide in an amount of about 0.25% by weight of the total composition.   
     
     
         63 . The method for preparing a pharmaceutical composition according to  claim 51 , further comprising the step of compressing said pharmaceutical composition into tablets. 
     
     
         64 . The method for preparing a pharmaceutical composition according to  claim 63 , further comprising the step of coating said tablets with a moisture barrier. 
     
     
         65 . The method for preparing a pharmaceutical composition according to  claim 64 , wherein the said moisture barrier is Opadry® II Blue.