Pharmaceutical suspension composition

Abstract

An aqueous oral liquid pharmaceutical composition system with reduced propensity for agglomeration and phase separation which is particularly amendable to the suspension of one or more pharmaceutical actives that are substantially insoluble in water. The oral liquid pharmaceutical composition may further comprise pharmaceutical actives that are soluble in water and dissolve in the aqueous medium. In the composition of the invention both suspended and any dissolved active agents are distributed homogeneously.

1 . An oral liquid pharmaceutical composition comprising: 
 a. a suspending system which comprises an aqueous composition which includes an aqueous medium, about 0.1 g/100 mL to about 0.5 g/100 mL xanthan gum and about 0.5 g/100 mL to about 3.0 g/100 mL microcrystalline cellulose/carboxymethylcellulose sodium;    b. at least one first pharmaceutical active which is substantially insoluble in the aqueous composition; and    c. a density adjusting agent.    
   
   
       2 . The pharmaceutical composition of  claim 1  further comprising at least one second pharmaceutical active which is soluble in the aqueous composition.  
   
   
       3 . The pharmaceutical composition of  claim 1  wherein the density adjusting agent comprises one or more polyol.  
   
   
       4 . The pharmaceutical composition of  claim 1  wherein the density adjusting agent comprises one or more of sorbitol, glycerin, propylene glycol, or a mixture thereof.  
   
   
       5 . The pharmaceutical composition of  claim 4  wherein the density adjusting agent comprises 10 g/100 mL to about 50 g/100 mL glycerin and about 10 g/100 mL to about 50 g/100 mL sorbitol.  
   
   
       6 . The pharmaceutical composition of  claim 1  further comprising about 0.1 g/100 mL to about 1.5 g/100 mL of a surface modifying agent.  
   
   
       7 . The pharmaceutical composition of  claim 1  wherein the at least one first pharmaceutical active is selected from the group consisting of Ibuprofen, Ketoprofen, Naproxen, Celecoxib, Rofecoxib, Valdecoxib, Nabumetone, Glimepiride, Diclofenac, Piroxicam, Meloxican and a mixture thereof.  
   
   
       8 . The pharmaceutical composition of  claim 1  wherein the at least one first pharmaceutical active is selected from the group consisting of ibuprofen, naproxen, ketoprofen, loratadine and a mixture thereof.  
   
   
       9 . The pharmaceutical composition of  claim 2  wherein the at least one second pharmaceutical active is selected from the group consisting of Fexofenadine (HCl), Chlorpheniramine (maleate), Brompheniramine (maleate), Diphenhydramine (HCl, Citrate), Cetirizine (HCl), Carbinoxamine (maleate), Loratadine, Desloratadine, Guaifenesin, Pseudoephedrine (HCL, Sulfate), Phenylpropanolamine (HCl), Ephedrine (HCl, Sulfate), phenylephrine, Dextromethorphan (HBr), Codine (Phosphate) and Hydrocodone (bitartrate) and a mixture thereof.  
   
   
       10 . The pharmaceutical composition of  claim 2  wherein the at least one second pharmaceutical active is selected from the group consisting of pseudoephedrine, phenylephrine, chlorpheniramine, dextromethorphan, brompheniramine, diphenhydramine and a mixture thereof.  
   
   
       11 . The pharmaceutical composition of  claim 2  further comprising about 0.1 g/100 mL to about 1.5 g/100 mL of a surface modifying agent.  
   
   
       12 . The pharmaceutical composition of  claim 11  wherein the surface modifying agent is a polysorbate.  
   
   
       13 . An oral liquid pharmaceutical composition comprising: 
 a. a suspending system which comprises an aqueous composition which includes an aqueous medium, about 0.1 g/100 mL to about 1.0 g/100 mL xanthan gum and about 0.5 g/100 mL to about 3.0 g/100 mL microcrystalline cellulose/carboxymethylcellulose sodium;    b. at least one first pharmaceutical active suspended in the aqueous composition;    c. at least one second pharmaceutical active soluble in the aqueous composition; and    d. a density adjusting agent.    
   
   
       14 . The pharmaceutical composition of  claim 1  wherein the at least one first pharmaceutical active is selected from the group consisting of Ibuprofen, Ketoprofen, Naproxen, Celecoxib, Rofecoxib, Valdecoxib, Nabumetone, Glimepiride, Diclofenac, Piroxicam, Meloxican and a mixture thereof.  
   
   
       15 . The pharmaceutical composition of  claim 13  wherein the at least one suspended first pharmaceutical active is selected from the group consisting of ibuprofen, naproxen, ketoprofen, loratadine, and a mixture thereof.  
   
   
       16 . The pharmaceutical composition of  claim 15  wherein ibuprofen is the suspended pharmaceutical active and is present in the pharmaceutical composition in an amount of about 1 g/100 mL to about 3 g/100 mL.  
   
   
       17 . The pharmaceutical composition of  claim 13  wherein the at least one second pharmaceutical active is selected from the group consisting of Fexofenadine (HCl), Chlorpheniramine (maleate), Brompheniramine (maleate), Diphenhydramine (HCl, Citrate), Cetirizine (HCl), Carbinoxamine (maleate), Loratadine, Desloratadine, Guaifenesin, Pseudoephedrine (HCL, Sulfate), phenylephrine, Phenylpropanolamine (HCl), Ephedrine (HCl, Sulfate), Dextromethorphan (HBr), Codine (Phosphate) and Hydrocodone (bitartrate) and a mixture thereof.  
   
   
       18 . The pharmaceutical composition of  claim 13  in which the at least one second pharmaceutical active soluble in the aqueous composition is selected from the group consisting of pseudoephredine, phenylephrine, chlorpheniramine, dextromethorphan, brompheniramine, diphenhydramine and a mixture thereof.  
   
   
       19 . The pharmaceutical composition of  claim 18  wherein the at least one second pharmaceutical active soluble in the aqueous composition includes pseudoephredrine in the amount of about 0.2 g/100 mL to about 0.4 g/100 mL and chlorpheniramine in the amount of about 0.01 g/100 mL to about 0.03 g/100 mL.  
   
   
       20 . The pharmaceutical composition of  claim 13  wherein the density adjusting agent comprises 10 g/100 mL to about 50 g/100 mL glycerin and about 10 g/100 mL to about 50 g/100 mL sorbitol.  
   
   
       21 . The pharmaceutical composition of  claim 13  further comprising about 0.1 g/100 mL to about 1.5 g/100 mL of a surface modifying agent.  
   
   
       22 . The pharmaceutical composition of  claim 21  wherein the surface modifying agent is a polysorbate.  
   
   
       23 . An oral liquid pharmaceutical composition comprising: 
 a. a suspending system which comprises an aqueous composition which includes an aqueous medium, and at least one of about 0.1 g/100 mL to about 0.5 g/100 mL xanthan gum and about 0.5 g/100 mL to about 3.0 g/100 mL microcrystalline cellulose/carboxymethylcellulose sodium;    b. at least one first pharmaceutical active which is substantially insoluble in the aqueous composition; and    c. a density adjusting agent.    
   
   
       24 . A method for treatment of pain and discomfort associated with at least one of headache, body ache, cold symptoms, flu symptoms, and allergy symptoms in humans comprising the administration to a human of a safe and effective amount of the pharmaceutical composition of  claim 1 ,  13  or  23 .  
   
   
       25 . A method of preparing an oral liquid pharmaceutical composition comprising: 
 a. preparing a suspending system, including suspended components in an aqueous medium;    b. suspending at least one substantially insoluble first pharmaceutical active in the suspending system; and    c. matching the true density of the at least one substantially insoluble first pharmaceutical active and the suspended components of the suspending system with the specific gravity of the aqueous medium.    
   
   
       26 . The method of  claim 25  further comprising de-aerating the composition by subjecting it to vacuum.  
   
   
       27 . The method of  claim 25  further comprising dissolving in the aqueous medium at least one second pharmaceutical active soluble in the aqueous medium.  
   
   
       28 . The method of  claim 26  further comprising adding a surface modifying agent to the pharmaceutical composition.