Stable glassy state powder formulations

Abstract

A powdered, dispersible composition having stable dispersibility over time is provided. The composition exhibits a characteristic glass transition temperature (T g ) and a recommended storage temperature (T s ), wherein the difference between T g and T s is at least about 10° C. (i.e. T g −T s is greater than 10° C.). The composition comprises a mixture of a pharmaceutically-acceptable glassy matrix and at least one pharmacologically active material within the glassy matrix. It may be further mixed with a powdered, pharmaceutically-acceptable carrier. It is particularly valuable in unit dosage form having a moisture barrier, in combination with appropriate labelling instructions. A process for producing a powdered dispersible composition is also provided, wherein the process comprises removing the solvent from a solution comprising a solvent, a glass former and a pharmacologically active material under conditions sufficient to form a glassy matrix having the pharmacologically active material within the matrix.

What is claimed is:  
     
         1 . A powdered, dispersible composition having stable dispersibility over time, a characteristic glass transition temperature (T g ) and a recommended storage temperature (T s ), wherein the difference between T g  and T s  is at least about 10° C., which composition comprises a mixture of 
 a pharmaceutically-acceptable glassy matrix and  
 at least one pharmacologically active material within the glassy matrix.  
 
     
     
         2 . A powdered dispersible composition in unit dosage form having stable dispersibility over time and a characteristic glass transition temperature (T g ), in combination with labelling instructions for treating pulmonary or systemic disease in a mammalian subject that include a recommended storage temperature (T s ), wherein the difference between T g  and T s  is at least about 10° C., which composition comprises a pharmaceutically acceptable glassy matrix and at least one pharmaceutically active material within the amorphous glassy matrix.  
     
     
         3 . The composition of  claim 1  or  2 , wherein the difference between T g  and T s  is at least about 20° C.  
     
     
         4 . The composition of  claim 1  or  2 , wherein the difference between T g  and T s  is at least about 30° C.  
     
     
         5 . The composition of  claim 1  or  2 , wherein the T g  is about 35° C. to about 200° C.  
     
     
         6 . The composition of  claim 1  or  2 , wherein the T g  is greater than about 45° C.  
     
     
         7 . The composition of  claim 1  or  2 , wherein the T g  is greater than about 55° C.  
     
     
         8 . The composition of  claim 1  or  2 , wherein T s  is about 2° C. to about 30° C. and T g  is about 22° C. to about 200° C.  
     
     
         9 . The composition of  claim 1  or  2 , wherein the glassy matrix comprises a glass former chosen from the group consisting of carbohydrates, carbohydrate derivatives, carbohydrate polymers, organic carboxylic salts, synthetic organic polymers, proteins, peptides, amino acids and mixtures thereof.  
     
     
         10 . The composition of  claim 1  or  2 , wherein the glass former is sodium citrate, raffinose, lactose, trehalose, maltotriose, maltodextrin, maltose, glucopyranosyl-sorbitol, glucopyranosyl-mannitol, polydextrose, sucrose cyclodextrin, casein, HSA, hydroxyethyl starch, stachyose, magnesium gluconate, cellobiose, or a mixture of two or more of the foregoing.  
     
     
         11 . A process for producing a powdered dispersible composition having stable dispersibility over time, a characteristic glass transition temperature (T g ) and a recommended storage temperature (T s ) wherein the difference between T g  and T s  is at least about 10° C., which process comprises removing the solvent from a solution comprising a solvent, a glass former and a pharmacologically active material under conditions sufficient to form a glassy matrix having the pharmacologically active material within the matrix.  
     
     
         12 . The process of  claim 11 , wherein the solvent is removed by spray drying.  
     
     
         13 . The process of  claim 11 , wherein the solvent is removed by evaporative drying.  
     
     
         14 . The process of  claim 11 , wherein the solvent is removed by chemical precipitation.  
     
     
         15 . The process of  claim 11 , wherein the solvent is water.  
     
     
         16 . The process of  claim 11 , wherein the solvent is ethanol.  
     
     
         17 . A powdered, dispersible composition having stable dispersibility over time, which composition comprises 
 (a) a first, respirable powdered component having a characteristic glass transition temperature (T g ) and a recommended storage temperature (T s ), wherein the difference between T g  and T s  is at least about 10° C., which composition comprises a mixture of 
 a pharmaceutically-acceptable glassy matrix and  
 at least one pharmacologically active material within the glassy matrix, and  
   (b) a second, nonrespirable powdered component comprising a powdered, pharmaceutically-acceptable carrier.    
     
     
         18 . The composition of  claim 17 , wherein the largest particle size of the first component is about 10 microns, with the majority of the particles between about 1 micron to about 5 microns, and the particle size of the second component is between about 15 microns to about 100 microns.  
     
     
         19 . The combination of  claim 2 , wherein the unit dosage form includes a moisture barrier.