Novel cocrystallization
AssigneeS.S.C.I., Inc.
InventorScott L. Childs
Life of this patent
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Abstract
The present disclosure relates to novel cocrystals and novel methods for cocrystallization. In particular, the disclosure includes cocrystals comprising a salt of an active agent, such as a chloride salt of an active pharmaceutical ingredient. The present disclosure also relates to methods of preparing cocrystals and methods for screening for solid state phases.
Claims68
A cocrystal comprising a salt and a neutral guest, wherein the salt comprises an active agent and a counterion, wherein the guest is a carboxylic acid having at least three carbon atoms, and the cocrystal is not a solvate.
A cocrystal comprising a salt and a neutral guest, wherein the salt comprises an active agent and a counterion, wherein the guest is a strong hydrogen bond donor and is selected from the guests set forth in Table 3.
A cocrystal comprising a salt and a neutral guest, wherein the salt comprises an active agent and a counterion, and wherein the counterion is not a chloride ion.
A cocrystal comprising a guest and an active agent, wherein the guest is an amine salt which provides a counterion, and the active agent is a carboxylic acid.
A method of generating a cocrystal comprising:
- adding aminor amount of an organic solvent separately to a solid active agent and a guest;
- melting the active agent to form a solution of the API and the organic solvent;
- melting the guest to form a solution of the guest and the organic solvent;
- forming a mixture of the two solutions;
- and
- solidifying the resulting mixture to form a cocrystal of the active agent and the guest.
A method of preparing a cocrystal of a salt of an active agent and a guest, said method comprising:
- selecting a salt of an active agent, wherein said salt comprises the active agent and a counterion;
- theorizing coordination of the counterion by hydrogen bond interactions within said crystal;
- selecting a guest to coordinate more strongly with the counterion than the coordination within said crystal;
- preparing a solution, melt or physical mixture comprising the active agent, the counterion, and the guest;
- subjecting the solution or melt to a crystallization process, or the physical mixture to grinding;
- forming a cocrystal comprising the salt of the active agent and the guest, wherein the counterion is coordinated with the guest through strong hydrogen bond interactions.
A method of modifying one or more physical properties of a drug formulation, the drug formulation comprising an API, said method comprising:
- forming cocrystals of the API with a plurality of guests;
- measuring at least one physical property of said cocrystals;
- assessing the effect of each guest on said at least one physical property;
- and
- preparing the drug formulation from one of said cocrystals having a desired physical property.
A method of preparing a cocrystalline pharmaceutical composition, said method comprising:
- obtaining a salt of an active pharmaceutical ingredient, wherein the salt has a negative counterion other than chloride;
- substituting chloride for the negative counterion in the obtained salt;
- and
- cocrystallizing the substituted salt with a suitable guest.
A method of preparing a cocrystal from a hydrate, wherein the cocrystal comprises a salt and a neutral guest, and wherein the salt comprises an active agent and a counterion, said method-comprising:
- providing a hydrate of the salt comprising water of hydration;
- selecting a guest to coordinate with the counterion;
- preparing a solution, melt or physical mixture comprising the hydrate and the guest;
- subjecting the solution or melt to a crystallization process or the physical mixture to grinding;
- and
- forming a cocrystal comprising the salt of the active agent and the guest.
A method of preparing a cocrystal from a solvate, wherein the cocrystal is not a solvate and comprise a salt and a neutral guest, and wherein the salt comprises an active agent and a counterion, said method comprising:
- providing a solvate of the salt comprising solvent molecules coordinated with the salt;
- selecting a guest to coordinate more strongly with the counterion than the solvent;
- preparing a solution, melt or physical mixture comprising the solvate and the guest;
- subjecting the solution or melt to a crystallization process or the physical mixture to grinding;
- and
- forming a cocrystal comprising the salt of the active agent and the guest.
Dependencies are inferred from the claim text.