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 oxybutynin that are not mechanically micronized.  
     
     
         2 . The pharmaceutical composition of  claim 1  wherein the microparticles of oxybutynin have mean dimensions of about 100 nm to about 10 μm.  
     
     
         3 . The composition of  claim 1  wherein at least about 75 weight-% of the oxybutynin of a sample of the composition comprising 100 mg of oxybutynin 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 50 RPM in a medium consisting essentially of 100 mL of 50 mM aqueous phosphate buffer, pH ˜6.8.  
     
     
         4 . The pharmaceutical composition of  claim 1  wherein at least about 60 weight-% of the oxybutynin of the sample of the composition comprising 100 mg of oxybutynin dissolves from the composition within about 90 minutes when dissolution is measured at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 50 RPM in a medium consisting essentially of 100 mL of 50 mM aqueous phosphate buffer, pH ˜6.8.  
     
     
         5 . The pharmaceutical composition of  claim 1  wherein at least about 20 weight-% of the oxybutynin of the sample of the composition comprising 100 mg of oxybutynin 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 50 RPM in a medium consisting essentially of 100 mL of 50 mM aqueous phosphate buffer, pH 6.8.  
     
     
         6 . A pharmaceutical composition comprising microparticles of oxybutynin that have not been micronized by a mechanical process selected from high energy milling and high pressure homogenization, from which pharmaceutical composition about 75 weight-% of the oxybutynin of a sample of the composition comprising 100 mg of oxybutynin 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 50 RPM in a medium consisting essentially of 100 mL of 50 mM aqueous phosphate buffer, pH ˜6.8.  
     
     
         7 . The pharmaceutical composition of  claim 6  wherein the microparticles of oxybutynin have mean dimensions of about 100 nm to about 10 μm.  
     
     
         8 . The pharmaceutical composition of  claim 6  wherein about 60 weight-% of the oxybutynin of the sample of the composition comprising 100 mg of oxybutynin dissolves from the composition within about 90 minutes when dissolution is measured at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 50 RPM in a medium consisting essentially of 100 mL of 50 mM aqueous phosphate buffer, pH ˜6.8.  
     
     
         9 . The pharmaceutical composition of  claim 6  wherein about 20 weight-% of the oxybutynin of the sample of the composition comprising 100 mg of oxybutynin 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 50 RPM in a medium consisting essentially of 100 mL of 50 mM aqueous phosphate buffer, pH ˜6.8.  
     
     
         10 . A pharmaceutical composition comprising microparticles of oxybutynin obtained by sublimation of a sublimable carrier from a solid solution of oxybutynin in the sublimable carrier.  
     
     
         11 . The pharmaceutical composition of  claim 10  wherein the microparticles of oxybutynin have mean dimensions of about 100 nm to about 10 μm.  
     
     
         12 . The composition of  claim 10  from which pharmaceutical composition the oxybutynin has a dissolution rate of: 
 about 20 weight-% dissolved within about 30 minutes, or    about 60 weight-% dissolved within about 90 minutes, or    about 75 weight-% dissolved within about 180 minutes when dissolution is measured on a sample of the composition comprising 100 mg of oxybutynin, at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 50 RPM in a medium consisting essentially of 100 mL of 50 mM aqueous phosphate buffer, pH ˜6.8.    
     
     
         13 . The pharmaceutical composition of  claim 10  wherein at least about 20 weight-% of the oxybutynin of a sample of the composition comprising 100 mg of oxybutynin 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 50 RPM in a medium consisting essentially of 100 mL of 50 mM aqueous phosphate buffer, pH ˜6.8.  
     
     
         14 . The pharmaceutical composition of  claim 10  wherein at least about 60 weight-% of the oxybutynin of a sample of the composition comprising 100 mg of oxybutynin dissolves from the composition within about 90 minutes when dissolution is measured at 37° C. with an apparatus II dissolution tester as described in the United States Pharmacopoeia operating at about 50 RPM in a medium consisting essentially of 100 mL of 50 mM aqueous phosphate buffer, pH ˜6.8.  
     
     
         15 . The pharmaceutical composition of  claim 10  wherein at least about 75 weight-% of the oxybutynin of a sample of the composition comprising 100 mg of oxybutynin 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 50 RPM in a medium consisting essentially of 100 mL of 50 mM aqueous phosphate buffer, pH ˜6.8.  
     
     
         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 one or more pharmaceutical carrier particles consisting essentially of a 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 oxybutynin that are obtained by sublimation of a sublimable carrier from a solid solution of oxybutynin in the sublimable carrier, wherein at least about 75 weight-% of the oxybutynin of a sample of the composition comprising 100 mg of oxybutynin dissolves from the pharmaceutical composition within at most 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 50 RPM in a medium consisting essentially of 100 mL of 50 mM aqueous phosphate buffer, pH ˜6.8.  
     
     
         22 . The pharmaceutical composition of  claim 21  wherein the microparticles of oxybutynin have mean dimensions 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 an oxybutynin delivery vehicle comprising the steps of: 
 a) forming a solid solution of oxybutynin 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 oxybutynin on the surface of the pharmaceutical carrier particle to obtain the oxybutynin delivery vehicle.