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 cyclosporin that are not mechanically micronized.  
     
     
         2 . The pharmaceutical composition of  claim 1  wherein the microparticles of cyclosporin have mean dimensions of about 100 nm to about 10 μm.  
     
     
         3 . The pharmaceutical composition of  claim 1  wherein at least about 9 weight-% of the cyclosporin of a sample of the composition comprising 10 mg of cyclosporin 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.  
     
     
         4 . The pharmaceutical composition of  claim 1  wherein at least about 12 weight-% of the cyclosporin of a sample of the composition comprising 10 mg of cyclosporin 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.  
     
     
         5 . The pharmaceutical composition of  claim 1  wherein at least about 14 weight-% of the cyclosporin of a sample of the composition comprising 10 mg of cyclosporin dissolves from the composition within about 180 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 cyclosporin that have not been micronized by a mechanical process selected from high energy milling and high pressure homogenization, from which pharmaceutical composition at least about 9 weight-% of the cyclosporin of a sample of the composition comprising 10 mg of cyclosporin 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.  
     
     
         7 . The pharmaceutical composition of  claim 6  wherein the microparticles of cyclosporin have mean dimensions of about 100 nm to about 10 μm.  
     
     
         8 . The pharmaceutical composition of  claim 6  wherein about 12 weight-% of the cyclosporin of a sample of the composition comprising 10 mg of cyclosporin 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.  
     
     
         9 . The pharmaceutical composition of  claim 6  wherein about 14 weight-% of the cyclosporin of a sample of the composition comprising 10 mg of cyclosporin dissolves from the composition within about 180 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 cyclosporin obtained by sublimation of a sublimable carrier from a solid solution of cyclosporin in the sublimable carrier.  
     
     
         11 . The pharmaceutical composition of  claim 10  wherein the composition comprises microparticles of cyclosporin having mean dimensions of about 100 nm to about 10 μm.  
     
     
         12 . The pharmaceutical composition of  claim 10  from which pharmaceutical composition the cyclosporin has a dissolution rate of: 
 about 9 weight-% dissolved within about 30 minutes,    about 12 weight-% dissolved within about 60 minutes, or    about 14% weight % dissolved within about 180 minutes    when dissolution is measured on a sample of the composition comprising 10 mg of cyclosporin 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 . A pharmaceutical composition of  claim 10  wherein at least about 9 weight-% of the cyclosporin of a sample of the composition comprising 10 mg of cyclosporin 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.  
     
     
         14 . A pharmaceutical composition of  claim 10  wherein at least about 12 weight-% of the cyclosporin of a sample of the composition comprising 10 mg of cyclosporin 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.  
     
     
         15 . A pharmaceutical composition of  claim 10  wherein at least about 14 weight-% of the cyclosporin of a sample of the composition comprising 10 mg of cyclosporin dissolves from the composition within about 180 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.  
     
     
         16 . 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.  
     
     
         17 . The pharmaceutical composition of  claim 16  wherein the sublimable carrier is menthol.  
     
     
         18 . The pharmaceutical composition of  claim 10  wherein the microparticles are deposited on at least one or a plurality of pharmaceutical carrier particles.  
     
     
         19 . The pharmaceutical composition of  claim 10  wherein the microparticles are deposited on at least one or a plurality of pharmaceutical carrier particles consisting essentially of non-hydrosoluble material.  
     
     
         20 . The pharmaceutical composition of  claim 19  wherein the non-hydrosoluble material is microcrystalline cellulose.  
     
     
         21 . A pharmaceutical composition comprising pharmaceutical carrier particles consisting essentially of a non-hydrosoluble material and, deposited thereon, microparticles of cyclosporin that are obtained by sublimation of a sublimable carrier from a solid solution of cyclosporin in the sublimable carrier, wherein about 9 weight-% of the cyclosporin of a sample of the composition comprising 10 mg of cyclosporin dissolves from the composition 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.  
     
     
         22 . The pharmaceutical composition of  claim 21  wherein the microparticles have a mean dimension of about 100 nm to about 10 μm.  
     
     
         23 . The pharmaceutical composition of  claim 10  wherein the microparticles are deposited on one or more pharmaceutical carrier particles consisting essentially of a hydrosoluble material.  
     
     
         24 . The pharmaceutical composition of  claim 23  wherein the hydrosoluble material is selected from the group consisting of sugar particles and lactose particles.  
     
     
         25 . A process for preparing a cyclosporin delivery vehicle comprising the steps of: 
 a) forming a solid solution of cyclosporin 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 cyclosporin on the surface of the pharmaceutical carrier particle to obtain the cyclosporin delivery vehicle.