Sapropterin Formulation

Abstract

The present disclosure relates to a formulation of sapropterin. The formulation comprises a solid suspension of sapropterin dispersed within an oil. Methods of treatment using the formulation are also contemplated by the present disclosure.

1 . A formulation comprising:
 particulate sapropterin in an oil, wherein the sapropterin is present in an amount from about 1 to about 50% w/v.   
     
     
         2 . The formulation of  claim 1 , wherein the sapropterin is present in an amount from about 1 to about 30% w/v. 
     
     
         3 . The formulation of  claim 1 , wherein the particulate sapropterin has a Dv90 from about 170 μm to about 400 μm. 
     
     
         4 . The formulation of  claim 1 , wherein the formulation is a homogenous dispersion upon agitation of the formulation. 
     
     
         5 . The formulation of  claim 1 , wherein the oil has a viscosity from about 10 to about 500 mPa·s. 
     
     
         6 . The formulation of  claim 1 , wherein the formulation further comprises a thickening agent. 
     
     
         7 . The formulation of  claim 6 , wherein the thickening agent is colloidal silica. 
     
     
         8 . The formulation of  claim 1 , further comprising an oil miscible excipient. 
     
     
         9 . The formulation of  claim 8 , wherein the oil miscible excipient comprises an alcohol, glycerol, polypropylene glycol, polyethyleneglycol, or combinations thereof. 
     
     
         10 . The formulation of  claim 1 , wherein the oil comprises a fatty acid, fatty acid glyceride, a polyol, a polyethylene glycol, a polypropylene glycol, a mineral oil, a plant derived oil, a mono-glyceride, di-glyceride, tri-glyceride, or combinations thereof. 
     
     
         11 . The formulation of  claim 1 , wherein the oil comprises about 50% to about 80% caprylic acid triglyceride (C8) and about 20% to about 50% capric acid triglyceride (C10). 
     
     
         12 . The formulation of  claim 1 , wherein the formulation further comprises a flavoring. 
     
     
         13 . The formulation of  claim 1 , wherein the formulation comprises a detectable amount of Compound 1 but no more than about 0.5% of Compound 1 with respect to a peak area of sapropterin as measured by HPLC after 1 month, after 3 months, after 6 months, after 9 months, or after 12 months of storage at 25° C. and 60% relative humidity or 40° C. and 75% relative humidity 
       
         
           
           
               
               
           
         
       
     
     
         14 . The formulation of  claim 1 , wherein the formulation comprises a detectable amount of Compound 2 but no more than about 0.5% of Compound 1 with respect to a peak area of sapropterin as measured by HPLC after 1 month, after 3 months, after 6 months, after 9 months, or after 12 months of storage at 25° C. and 60% relative humidity or 40° C. and 75% relative humidity 
       
         
           
           
               
               
           
         
       
     
     
         15 . The formulation of  claim 1 , wherein the formulation comprises a detectable amount of Compounds 1 and 2 but no more than about 1% of Compounds 1 and 2 with respect to a peak area of sapropterin as measured by HPLC after 1 month, after 3 months, after 6 months, after 9 months, or after 12 months of storage at 25° C. and 60% relative humidity or 40° C. and 75% relative humidity. 
     
     
         16 . The formulation of  claim 1 , wherein the formulation comprises a detectable amount of Compound 3 but no more than about 0.2% of Compound 3 with respect to a peak area of sapropterin as measured by HPLC after 1 month, after 3 months, after 6 months, after 9 months, or after 12 months of storage at 25° C. and 60% relative humidity or 40° C. and 75% relative humidity 
       
         
           
           
               
               
           
         
       
     
     
         17 . The formulation of  claim 1 , wherein the formulation comprises a detectable amount of impurities but no more than about 1.5% of total impurities with respect to a peak area of sapropterin as measured by HPLC after 1 month, after 3 months, after 6 months, after 9 months, or after 12 months of storage at 25° C. and 60% relative humidity or 40° C. and 75% relative humidity. 
     
     
         18 . (canceled) 
     
     
         19 . A method of treatment for phenylketonuria or hyperphenylalaninemia, wherein the method comprises administering a therapeutically effective amount of the formulation of  claim 1  to a patient in need thereof. 
     
     
         20 . The method of treatment of  claim 19 , wherein the treatment is for pediatric phenylketonuria or pediatric hyperphenylalaninemia.