Pamoate salt of monoamine anti-parkinson's agents, method of preparation and use thereof

Abstract

In various embodiments, provided herein are pamoate salts of monoamine Anti-Parkinsons disease agents including rotigotine, ropinirole, pramipexole, selegiline, rasagiline, and safinamide, pharmaceutical composition comprising the same, methods of preparing the same, and methods of using the same. For example, the pamoate salt herein can be characterized by a molar ratio of rotigotine, ropinirole, pramipexole, selegiline, rasagiline, or safinamide to pamoic acid of about 1:1 or about 2:1. The pamoate salt herein can also be crystalline including anhydrous, hydrate or solvate forms, or their polymorphs, or amorphous. The pamoate salts described herein can provide a long acting and/or extended release profile of the monoamine agents tor the treatment of Parkinsons disease (PD). Thus, also provided herein are methods of preparing a long acting and/or extended release injectable formulation of the monoamine agents using their respective pamoate salts. And in some embodiments, provided herein are methods of treating a subject in need thereof comprising administering a pharmaceutical composition comprising a pamoate salt of rotigotine, ropinirole, pramipexole, selegiline, rasagiline, and/or safinamide.

1 - 65 . (canceled) 
     
     
         66 . A method of treating Parkinson's disease, comprising administering to a subject in need thereof a pharmaceutical composition comprising a pamoate salt of a monoamine anti-Parkinson's disease agent and a pharmaceutically acceptable carrier. 
     
     
         67 . The method of  claim 66 , wherein the pharmaceutically acceptable carrier is a viscous aqueous or nonaqueous carrier. 
     
     
         68 . The method of  claim 66 , wherein the pharmaceutical composition is administered by injection. 
     
     
         69 . The method of  claim 67 , wherein administering the pharmaceutical composition provides a duration of efficacy of the monoamine for least about 7 days. 
     
     
         70 . The method of  claim 66 , wherein the pharmaceutical composition comprises a crystalline Form I of pamoate salt of rotigotine, which is characterized by an X-ray Powder diffraction (“XRPD”) spectrum having both peaks at 4.6 and 9.3, ±0.2° 2-theta. 
     
     
         71 . The method of  claim 66 , wherein the pharmaceutical composition comprises a crystalline form of pamoate salt of ropinirole, wherein the crystalline form is Form A, Form B, Form C, Form D, or Form E, wherein
 Form A is characterized by an XRPD spectrum having the following peaks: 4.3, 17.1, 18.6, and 20.5, ±0.2° 2-theta;   Form B is characterized by an XRPD spectrum having the following peaks: 11.5, 16.4, 21.0, 23.1, 23.4, and 26.2, ±0.2° 2-theta;   Form C is characterized by an XRPD spectrum having peaks at 16.1 and 18.8, ±0.2° 2-theta;   Form D is characterized by an XRPD spectrum having the following peaks: 14.3, 17.9, and 25.2, ±0.2° 2-theta; and   Form E is characterized by an XRPD spectrum having the following peaks: 11.7, 12.0, and 21.0, ±0.2° 2-theta.   
     
     
         72 . The method of  claim 66 , wherein the pharmaceutical composition comprises a crystalline form of pamoate salt of pramipexole, wherein the crystalline form is Form 1, Form 2, Form 3, or Form 4, wherein
 Form 1 is characterized by an XRPD spectrum having one or more of the following peaks: 13.8, 15.3, and 21.1, ±0.2° 2-theta;   Form 2 is characterized by an XRPD spectrum having one or more of the following peaks: 12.0, 15.0, 20.4, and 20.9, ±0.2° 2-theta;   Form 3 is characterized by an XRPD spectrum having one or more of the following peaks: 10.7, 12.7, 13.5, and 14.9, ±0.2° 2-theta; and   Form 4 is characterized by an XRPD spectrum having the following peaks: 6.1, and 17.9, ±0.2° 2-theta.   
     
     
         73 . The method of  claim 72 , wherein the crystalline form is Form 1, wherein the Form 1 is characterized by an XRPD spectrum having the following peaks: 7.7, 11.8, 13.8, 15.3, 18.9, 21.1, 23.1, 23.7, and 26.4, ±0.2° 2-theta. 
     
     
         74 . The method of  claim 72 , wherein the crystalline form is Form 2, wherein the Form 2 is characterized by an XRPD spectrum having the following peaks: 12.0, 15.0, 20.4, 20.9, 22.5, and 23.3, ±0.2° 2-theta. 
     
     
         75 . The method of  claim 72 , wherein the crystalline form is Form 3, wherein the Form 3 is characterized by an XRPD spectrum having the following peaks: 10.7, 12.7, 13.5, 14.9, 18.7, and 22.3, ±0.2° 2-theta. 
     
     
         76 . The method of  claim 72 , wherein the crystalline form is Form 4, wherein the Form 4 is characterized by (a) an XRPD spectrum having the following peaks: 6.1, 17.9, 21.3, and 23.2, ±0.2° 2-theta.