Complexing agent salt formulations of pharmaceutical compounds

Inventors

Becker, Jeffrey • Peterson, Gregg • Wallach, Jason

Abstract

Provided herein are pharmaceutical formulations and pharmaceutical compound salts which utilize complexing agents as counterions. Such formulations and salts are useful for treating a variety of disease and disorders.

Core Innovation

The invention relates to pharmaceutical compositions comprising a pharmaceutical compound, not ketamine, having a protonated nitrogen atom, together with an acid-substituted cyclodextrin complexing agent having a plurality of acidic functional groups that act as a counterion for the protonated nitrogen atom. The compositions are formulated as aqueous formulations for subcutaneous or intramuscular administration having a pH of at least about 5.5.

A central feature is that the osmolality of the pharmaceutical composition is lower than the osmolality of a composition comprising an equivalent amount of a freebase form of the pharmaceutical compound encapsulated within a hydrophobic core of a salt of the complexing agent. The formulations specify a molar ratio of the pharmaceutical compound to the complexing agent of at least 1:1, and the complexing agent is a substituted cyclodextrin, including conjugate base forms that function as the counterion.

Additional embodiments define stoichiometric relationships between the basic nitrogen atoms of the pharmaceutical compound and the acidic functional groups of the cyclodextrin. In one form, the total number of basic nitrogen atoms of the pharmaceutical compound is equal to the number of acidic functional groups of the complexing agent, and the compositions are also described as providing desirable pH without extra buffers and storage as powders with redissolution capability.

Claims Coverage

The consolidated claim coverage includes three independent claim sets. Across them, the inventive features center on a non-ketamine pharmaceutical compound having a protonated or basic nitrogen atom and an acid-substituted cyclodextrin complexing agent, including its conjugate base form, acting as a counterion, together with aqueous subcutaneous or intramuscular formulation at pH at least about 5.5, a molar ratio of at least 1:1, and reduced osmolality versus an equivalent freebase comparator; one claim set additionally requires stoichiometric matching of basic nitrogen atoms to acidic functional groups.

The claims collectively protect aqueous subcutaneous or intramuscular pharmaceutical compositions excluding ketamine, in which an acid-substituted cyclodextrin or its conjugate base provides acidic functional groups as counterions for protonated or basic nitrogen atoms, with pH at least about 5.5, a compound-to-complexing-agent molar ratio of at least 1:1, and reduced osmolality versus the stated freebase comparator; one independent claim also requires stoichiometric equality between basic nitrogen atoms and acidic functional groups.

Stated Advantages

Documented Applications