Drug microparticles

Abstract

Provided are microparticles of active pharmaceutical ingredients, drug delivery vehicles comprising same, and methods for making them.

1 . A pharmaceutical composition comprising microparticles of risperidone that are not mechanically micronized.  
     
     
         2 . The pharmaceutical composition of  claim 1  wherein the microparticles have mean dimensions of about 100 nm to about 10 μm.  
     
     
         3 . The pharmaceutical composition of  claim 1  wherein essentially all of the risperidone of the sample of the composition comprising 50 mg of risperidone dissolves from the composition within about 60 minutes when dissolution is measured at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 100 RPM in a medium consisting essentially of 900 mL water.  
     
     
         4 . The pharmaceutical composition of  claim 1  wherein essentially all of the risperidone of the sample of the composition comprising 50 mg of risperidone dissolves from the composition within about 30 minutes when dissolution is measured at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 100 RPM in a medium consisting essentially of 900 mL water.  
     
     
         5 . The pharmaceutical composition of  claim 1  wherein at least about 69 weight-% of the risperidone of the sample of the composition comprising 50 mg of risperidone dissolves from the composition within about 15 minutes when dissolution is measured at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 100 RPM in a medium consisting essentially of 900 mL water.  
     
     
         6 . A pharmaceutical composition comprising microparticles of risperidone that have not been micronized by a mechanical process selected from high energy milling and high pressure homogenization, from which pharmaceutical composition essentially all of the risperidone of a sample of the composition comprising 50 mg of risperidone dissolves within not more than about 60 minutes when dissolution is measured at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 100 RPM in a medium consisting essentially of 900 mL water.  
     
     
         7 . The pharmaceutical composition of  claim 6  wherein the microparticles of risperidone have mean dimensions of about 100 nm to about 10 μm.  
     
     
         8 . The composition of  claim 6 , wherein essentially all of the risperidone of a sample of the composition comprising 50 mg of risperidone dissolves within not more than about 30 minutes when dissolution is measured at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 100 RPM in a medium consisting essentially of 900 mL water.  
     
     
         9 . The pharmaceutical composition of  claim 5  wherein about 69 weight-% of the risperidone of the sample of the composition comprising 50 mg of risperidone dissolves from the composition within about 15 minutes when dissolution is measured at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 100 RPM in a medium consisting essentially of 900 mL water.  
     
     
         10 . A pharmaceutical composition comprising microparticles of risperidone obtained by sublimation of a sublimable carrier from a solid solution of risperidone in the sublimable carrier.  
     
     
         11 . The pharmaceutical composition of  claim 10  wherein the microparticles of risperidone have mean dimensions of about 100 nm to about 10 μm.  
     
     
         12 . The pharmaceutical composition of  claim 10 , from which composition the risperidone has a dissolution rate of: 
 about 69 weight-% dissolved within about 15 minutes,    essentially all the risperidone dissolved within about 30 minutes, or    essentially all the risperidone dissolved within about 60 minutes    when dissolution is measured on a sample of the composition comprising 50 mg of risperidone at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 100 RPM in a medium consisting essentially of 900 mL water.    
     
     
         13 . The pharmaceutical composition of  claim 10  wherein essentially all of the risperidone of the sample of the composition comprising 50 mg of risperidone dissolves from the composition within not more than about 60 minutes when dissolution is measured at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 100 RPM in a medium consisting essentially of 900 mL water.  
     
     
         14 . The pharmaceutical composition of  claim 10  wherein essentially all of the risperidone of the sample of the composition comprising 50 mg of risperidone dissolves from the composition within about 30 minutes when dissolution is measured at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 100 RPM in a medium consisting essentially of 900 mL water.  
     
     
         15 . The pharmaceutical composition of  claim 10  wherein about 69 weight-% of the risperidone of the sample of the composition comprising 50 mg of risperidone dissolves within about 15 minutes, and essentially all of the risperidone of the sample dissolves within about 30 minutes or less when dissolution is measured at 37□ C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 100 rpm in a medium consisting essentially of 900 mL water.  
     
     
         16 . The pharmaceutical composition of  claim 10  wherein about 69 weight-% of the risperidone of the sample of the composition comprising 50 mg of risperidone dissolves from the composition within about 15 minutes when dissolution is measured at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 100 RPM in a medium consisting essentially of 900 mL water.  
     
     
         17 . The pharmaceutical composition of  claim 10  wherein the sublimable carrier is selected from the group consisting of menthol, thymol, camphor, t-butanol, trichloro-t-butanol, imidazole, coumarin, acetic acid (glacial), dimethylsulfone, urea, vanillin, camphene, salicylamide, and 2-aminopyridine.  
     
     
         18 . The pharmaceutical composition of  claim 17  wherein the sublimable carrier is menthol.  
     
     
         19 . The pharmaceutical composition of  claim 10  wherein the microparticles are deposited on at least one or a plurality of pharmaceutical carrier particles.  
     
     
         20 . The pharmaceutical composition of  claim 10  wherein the microparticles are deposited one or more pharmaceutical carrier particles consisting essentially of a non-hydrosoluble material.  
     
     
         21 . The pharmaceutical composition of  claim 20  wherein the non-hydrosoluble material is microcrystalline cellulose.  
     
     
         22 . A pharmaceutical composition comprising pharmaceutical carrier particles consisting essentially of a non-hydrosoluble material and, deposited thereon, microparticles of risperidone that are obtained by sublimation of a sublimable carrier from a solid solution of risperidone in the sublimable carrier, wherein essentially all of the risperidone of a sample of the composition comprising 50 mg of risperidone dissolves from the pharmaceutical composition within no more than about 60 minutes when dissolution is measured at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 100 RPM in a medium consisting essentially of 900 mL water.  
     
     
         23 . The pharmaceutical composition of  claim 21  wherein the microparticles of risperidone have mean dimensions of about 100 nm to about 10 μm.  
     
     
         24 . The pharmaceutical composition of  claim 10  wherein about 69 weight-% of the risperidone of the sample of the composition comprising 50 mg of risperidone dissolves within about 15 minutes, and essentially all of the risperidone of the sample dissolves within 30 minutes or less when dissolution is measured at 37□ C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 100 rpm in a medium consisting essentially of 900 mL water.  
     
     
         25 . The pharmaceutical composition of  claim 10  wherein the microparticles are deposited on one or more pharmaceutical carrier particles consisting essentially of a hydrosoluble material.  
     
     
         26 . The pharmaceutical composition of  claim 25  wherein the hydrosoluble material is selected from the group consisting of sugar particles and lactose particles.  
     
     
         27 . A process for preparing a risperidone delivery vehicle comprising the steps of: 
 a) forming a solid solution of risperidone and a sublimable carrier on the surface of a pharmaceutical carrier particle; and    b) subliming the sublimable carrier from the solid solution to deposit microparticles of risperidone on the surface of the pharmaceutical carrier particle to obtain the risperidone delivery vehicle.