Romidepsin solid forms and uses thereof

Abstract

The present disclosure provides solid forms of a compound of formula I. In some embodiments, the present disclosure provides crystalline forms of Compound I. In some embodiments, the present disclosure provides solvate forms of Compound I. In some embodiments, the present disclosure provides amorphous Compound I.

1 - 20 . (canceled) 
     
     
         21 . Amorphous romidepsin. 
     
     
         22 . The amorphous romidepsin of  claim 21 , wherein the amorphous romidepin is obtained from a water/dichloromethane mixture. 
     
     
         23 . The amorphous romidepsin of  claim 21 , wherein the amorphous romidepin is obtained from an isopropanol-trifluoroethanol/methanol mixture. 
     
     
         24 . The amorphous romidepsin of  claim 22 , wherein the amorphous romidepin exhibits a glass transition temperature of −91° C. 
     
     
         25 . The amorphous romidepsin of  claim 23 , wherein the amorphous romidepin exhibits a glass transition temperature of −91° C. 
     
     
         26 . The amorphous romidepsin of  claim 22 , wherein a thermogravimetric analysis (TGA) thermogram exhibits a weight loss of 3.5%. 
     
     
         27 . The amorphous romidepsin of  claim 23 , wherein a thermogravimetric analysis (TGA) thermogram exhibits a weight loss of 3.5%. 
     
     
         28 . A composition comprising amorphous romidepsin and an excipient, wherein the excipient is selected from the group consisting of a cellulose derivative, gum, dextran, acacia, vinyllactam, cyclodextrin, gelatin, hypromellose phthalate, sugar, sugar alcohol, polyhydric alcohol, polyethylene glycol (PEG) polymer, polyethylene oxide, polyethylene derivative, polyvinyl alcohol, propylene glycol derivative, sodium lauryl sulfate (SLS), Tween, methacrylic acid co-polymer, and an amino acid. 
     
     
         29 . The composition of  claim 28 , wherein the excipient is a cellulose derivative. 
     
     
         30 . The composition of  claim 29 , wherein the cellulose derivative is hydroxypropylmethyl cellulose (HPMC) polymer, hydroxypropyl cellulose, ethyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, or sodium carboxymethyl cellulose. 
     
     
         31 . The composition of  claim 29 , wherein the cellulose derivative is HPMC polymer. 
     
     
         32 . The composition of  claim 31  wherein the molecular weight of the HPMC polymer is in the range between about 10,000 and about 1,500,000 D. 
     
     
         33 . The composition of  claim 32 , wherein the molecular weight of the HPMC polymer is not greater than 1,000,000 D. 
     
     
         34 . The composition of  claim 32 , wherein the molecular weight of the HPMC polymer is not greater than 500,000 D. 
     
     
         35 . The composition of  claim 32 , wherein the molecular weight of the HPMC polymer is not greater than 150,000 D. 
     
     
         36 . The composition of  claim 31 , wherein the HPMC has a viscosity in water that is in a range between about 100 and about 100,000 cP measured at a concentration of 2% (w/w). 
     
     
         37 . The composition of  claim 36 , wherein the HPMC viscosity in water is in a range between about 1,000 and about 15,000 cP. 
     
     
         38 . The composition of  claim 37 , wherein the HPMC viscosity in water is about 4,000 cP. 
     
     
         39 . The composition of  claim 31 , wherein the HPMC polymer exhibits about 15% to about 35% methoxy substitution. 
     
     
         40 . The composition of  claim 39 , wherein the HPMC polymer exhibits about 19% to about 32% methoxy substitution. 
     
     
         41 . The composition of  claim 40 , wherein the HPMC polymer exhibits about 22% to about 30% methoxy substitution. 
     
     
         42 . The composition of  claim 31 , wherein the HPMC polymer exhibits about 3% to about 15% hydroxypropoxy substitution. 
     
     
         43 . The composition of  claim 42 , wherein the HPMC polymer exhibits about 4% to about 12% hydroxypropoxy substitution. 
     
     
         44 . The composition of  claim 43 , wherein the HPMC polymer exhibits about 7% to about 12% hydroxypropoxy substitution. 
     
     
         45 . The composition of  claim 31 , wherein the HPMC polymer is hydroxypropylmethyl cellulose (HPMC), hydroxypropylmethyl cellulose acetate phthalate (HPMC-AP), hydroxypropylmethyl cellulose acetate succinate (HPMC-AS), hydroxypropylmethyl cellulose acetate trimellitate (HPMC-AT) or hydroxypropylmethyl cellulose phthalate (HPMC-P). 
     
     
         46 . The composition of  claim 28 , wherein the excipient is a PEG polymer. 
     
     
         47 . The composition of  claim 46 , wherein the PEG polymer has a molecular weight of about 5,000 to about 20,000 D. 
     
     
         48 . The composition of  claim 28 , wherein the excipient is Tween®. 
     
     
         49 . The composition of  claim 48 , wherein the Tween® is Tween® 20, Tween® 40, Tween® 60, Tween® 65, or Tween® 80. 
     
     
         50 . A composition comprising amorphous romidepsin and an excipient, wherein the excipient is not polyvinylpyrrolidone (PVP).