PHARMACEUTICALLY ACCEPTABLE SALTS AND POLYMORPHIC FORMS OF HYDROCODONE BENZOIC ACID ENOL ESTER AND PROCESSES FOR MAKING SAME
Compositions comprising hydrocodone benzoic acid enol ester to form novel prodrugs including hydrocodone benzoic acid enol ester salts, and various polymorphs. Also provided are processes for the preparation of hydrocodone benzoic acid enol ester salts, and various polymorphs.
1 - 83 . (canceled)
84 . A process for the preparation of benzhydrocodone enol ester comprising the steps of:
(a) preparing a mixture comprising hydrocodone free base and a benzoylating reagent, and,
(b) heating the mixture to a temperature in the range of about 80° C. to about 160° C.
85 . The process of claim 84 , wherein the benzoylating reagent is selected from the group consisting of benzoic anhydride or benzoyl chloride.
86 . The process of claim 84 , wherein the mixture further comprises a suitable organic solvent.
87 . The process of claim 86 , wherein the suitable organic solvent is selected from the group consisting of toluene, dimethylformamide, N-methyl-2-pyrrolidinone, and xylenes.
88 . The process of claim 87 , wherein the suitable organic solvent is toluene.
89 . A process for the preparation of benzhydrocodone comprising the steps of:
(a) preparing a mixture comprising hydrocodone free base, benzoic anhydride, and toluene and,
(b) heating the mixture to a temperature in the range of about 80° C. to about 160° C.
90 . The process of claim 88 or 89 , wherein the toluene is substantially removed from the mixture via step b.
91 . The process of claim 84 , 88 , or 89 , wherein the temperature of step (b) is in the range of about 126° C. to about 132° C.
92 . The process of claim 84 , 88 , or 89 wherein the mixture further comprises a suitable base.
93 . The process of claim 92 , wherein the suitable base is selected from the group consisting of pyridine, N,N-diisopropylethylamine, diazabicycloundecene, trimethylamine, and potassium benzoate.
94 . The process of claim 84 , 88 , or 89 further comprising adding concentrated hydrochloric acid to the mixture.
95 . A pharmaceutical composition comprising a therapeutically effective amount of a benzhydrocodone enol ester prepared according to the process of claim 84 , 88 , or 89 and a pharmaceutically acceptable excipient.