Cocrystallization
View Patent ↗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.
1. A method of screening for a cocrystal of a hydrochloric acid salt of an active agent, comprising the steps of:
selecting a carboxylic acid having at least 4 carbons to coordinate via hydrogen bonding with the chloride anion of the hydrochloric acid salt of the active agent,
preparing a solution, melt, or physical mixture of the hydrochloric acid salt of the active agent and the carboxylic acid,
subjecting the solution or melt to a crystallization process, or the physical mixture to grinding, and
determining whether a cocrystal of the hydrochloric acid salt of the active agent and the carboxylic acid has formed.
2. The method of claim 1 wherein the carboxylic acid having at least 4 carbons is selected from benzoic acid, succinic acid, and fumaric acid.
3. The method of claim 1 wherein the active agent is an active pharmaceutical ingredient.
4. The method of claim 1 wherein the active agent is a nitrogen containing base.
5. The method of claim 4 wherein the nitrogen containing base is a tertiary amine.
6. The method of claim 4 wherein the nitrogen containing base is a secondary amine.
7. The method of claim 4 wherein the nitrogen containing base is a primary amine.
8. The method of claim 1 wherein x-ray diffraction is used to determine whether a cocrystal of the hydrochloric acid salt of the active agent and the carboxylic acid has formed.
9. The method of claim 1 wherein the preparing step comprises preparing a solution of the hydrochloric acid salt of the active agent and the carboxylic acid.
10. The method of claim 1 wherein the preparing step comprises preparing a melt of the hydrochloric acid salt of the active agent and the carboxylic acid.
11. The method of claim 1 wherein the preparing step comprises preparing a physical mixture of the hydrochloric acid salt of the active agent and the carboxylic acid.