Solvent system for enhancing the solubility of pharmaceutical agents

Abstract

Liquid and semi-solid pharmaceutical compositions, which can be administered in liquid form or can be used for preparing capsules, are described herein. The composition comprises the salt of one ore more active agents, polyethylene glycol, 0.2-1.0 mole equivalents of a de-ionizing agent per mole of active agent, and water. The pH of the composition is adjusted within the range of 2.5-7.5. The de-ionizing agent causes partial de-ionization (neutralization) of the salt of the active agent resulting in enhanced bioavailability of salts of weakly acidic, basic or amphoteric active agents as well as lesser amounts of polyethylene glycol (PEG) esters.

1 . A pharmaceutical composition comprising 
 (a) a salt of one or more pharmaceutically active agents; and    (b) a deionizing agent.    
     
     
         2 . The composition of  claim 1  wherein the pharmaceutically active agent is selected from the group consisting of therapeutically active agents, diagnostic agents, and prophylactic agents.  
     
     
         3 . The composition of  claim 1  wherein the deionizing agent is present in an amount from about 0.2 to 1.0 mole equivalents per mole of the pharmaceutically active agent(s).  
     
     
         4 . The composition of  claim 1  wherein the deionizing agent is selected from the group consisting of hydrogen ion and hydroxide ion.  
     
     
         5 . The composition of  claim 1  further comprising polyethylene glycol.  
     
     
         6 . The composition of  claim 5  wherein polyethylene glycol is present in an amount from about 10% to about 80% by weight  
     
     
         7 . The composition of  claim 5  wherein polyethylene glycol is one or more polyethylene glycols with a molecular weight between 300 and 1500.  
     
     
         8 . The composition of  claim 1  further comprising water.  
     
     
         9 . The composition of  claim 8  wherein water is present in an amount from about 1% to about 18% by weight.  
     
     
         10 . The composition of  claim 1  further comprising one or more excipients.  
     
     
         11 . The composition of  claim 7  wherein the excipients are selected from the group consisting of plasticizers, crystallization inhibitors, wetting agents, bulk filling agents, solubilizers, bioavailability enhancers, solvents, pH-adjusting agents, dyes, preservatives, solvents, surfactants, and combinations thereof.  
     
     
         12 . The composition of  claim 11  wherein the solubilizer is selected from the group consisting of glycerin, polyvinylpyrrolidone, propylene glycol and combinations thereof.  
     
     
         13 . The composition of  claim 12  wherein the solubilizer is present in amount from about 1% to about 10% by weight.  
     
     
         14 . A method of making a pharmaceutical composition comprising 
 a salt of one or more pharmaceutically active agents; and    a deionizing agent comprising    (a) mixing the salt of one or more pharmaceutically active agents, and the deionizing agent at an appropriate temperature; and    (b) encapsulating the mixture in a softgel capsule.    
     
     
         15 . The method of  claim 14  further comprising polyethylene glycol.  
     
     
         16 . The method of  claim 14  further comprising water.  
     
     
         17 . The method of  claim 14  wherein the appropriate temperature is from about 50° C. to about 70° C.  
     
     
         18 . A method of using a pharmaceutical composition comprising 
 (a) a salt of one or more pharmaceutically active agents; and    (b) a deionizing agent    comprising administering to a patient in need thereof the salt of one or more pharmaceutically active agents.    
     
     
         19 . A softgel capsule comprising a fill material wherein the fill material comprises 
 (a) a salt of one or more pharmaceutically active agents; and    (b) a deionizing agent.    
     
     
         20 . The capsule of  claim 19  wherein the pharmaceutically active agent is selected from the group consisting of therapeutically active agents, diagnostic agents, and prophylactic agents.  
     
     
         21 . The capsule of  claim 19  wherein the deionizing agent is present in an amount from about 0.2 to 1.0 mole equivalents per mole of the pharmaceutically active agent(s).  
     
     
         22 . The capsule of  claim 19  wherein the deionizing agent is selected from the group consisting of hydrogen ion and hydroxide ion.  
     
     
         23 . The capsule of  claim 19  further comprising polyethylene glycol.  
     
     
         24 . The capsule of  claim 23  wherein polyethylene glycol is present in an amount from about 10% to about 80% by weight  
     
     
         25 . The capsule of  claim 23  wherein polyethylene glycol is one or more polyethylene glycols with a molecular weight between 300 and 1500.  
     
     
         26 . The capsule of  claim 19  further comprising water.  
     
     
         27 . The capsule of  claim 26  wherein water is present in an amount from about 1% to about 18% by weight.  
     
     
         28 . The capsule of  claim 19  further comprising one or more excipients.  
     
     
         29 . The capsule of  claim 28  wherein the excipients are selected from the group consisting of plasticizers, crystallization inhibitors, wetting agents, bulk filling agents, solubilizers, bioavailability enhancers, solvents, pH-adjusting agents, dyes, preservatives, solvents, surfactants, and combinations thereof.  
     
     
         30 . The capsule of  claim 29  wherein the solubilizer is selected from the group consisting of glycerin, polyvinylpyrrolidone, propylene glycol and combinations thereof.  
     
     
         31 . The capsule of  claim 29  wherein the solubilizer is present in amount from about 1% to about 10% by weight.