Cyclosporin analog formulations

Abstract

The present disclosure relates to formulations containing cyclosporin analogs that are structurally similar to cyclosporin A, in particular isomeric mixtures of cyclosporin analogs that are structurally similar to cyclosporin A. The formulations form stable microemulsion preconcentrates and may provide superior drug bioavailability and/or may reduce one or more adverse effects associated with the administration of cyclosporin. Also disclosed are methods for using and preparing the formulations.

1 . A pharmaceutical composition comprising:
 a) a pharmaceutically effective amount of ISA Tx 247;   b) Tween 80;   c) Vitamin E TPGS;   d) ethanol; and   e) isopropyl myristate;   wherein the pharmaceutical composition is a microemulsion or a microemulsion preconcentrate.   
     
     
         2 . The pharmaceutical composition of  claim 1  which comprises from about 5% to about 10% by weight of ISA Tx 247, from about 20% to about 50% by weight of Vitamin E TPGS, from about 5% to about 55% by weight of isopropyl myristate, from about 5% to about 50% by weight of Tween 80, and about 5% to about 15% by weight of ethanol. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the composition is a liquid microemulsion preconcentrate at room temperature. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the ratio by weight of ISA Tx 247: Tween 80: Vitamin E TPGS: ethanol: isopropy myristate is about 0.5-1:2:1:1:6. 
     
     
         5 . A method of producing immunosuppression, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of  claim 1 . 
     
     
         6 . A method of preparing the pharmaceutical composition of  claim 1 , comprising mixing the isopropyl myristate, the Tween 80, the ethanol, the Vitamin E TPGS, and the pharmaceutically effective amount of ISA Tx 247 until the ISA Tx 247 is completely dissolved.