Cocrystal and Salt Screening of Imipramine

EXAMPLE 12

Cocrystal and salt screening of imipramine hydrochloride is carried out using the following procedures. Solutions of imiprimine hydrochloride and various guests are prepared in acetonitrile, methanol, aqueous ethanol, and acetone in 1:1 molar ratios having a concentrations of about 10 mg/mL. The guests include benzoic acid, gallic acid, and 2,5-dihydroxybenzoic acid. Aliquots of 100 microliters of the solutions are placed in different wells of 96-well polypropylene plates that have thin walls. The plates are sonicated for 1 minute in a sonication bath after the volume of the solutions are reduced to the point where both components are supersaturated. This concentration is calculated based on the solubility of the individual components. The sonication is repeated every hour for 24 hours as the solutions continue to evaporate. A duplicate set of well plates is allowed to evaporate at room temperature without sonication.

Solids are present in most of the wells and are analyzed in situ, automatically by transmission x-ray powder diffraction through the well plates. It is expected that a number of cocrystals and/or salts are present in the sonicated plates and that different polymorphs, hydrates, solvates, desolvates, and dehydrates of the cocrystals and/or salts may also be present. It is expected that solids in the unsonicated plates will have a different variety of solid forms present compared to the sonicated samples and that there will not be as many cocrystals and/or salts formed.

All patents, test procedures, and other documents cited herein, including priority documents, are fully incorporated by reference to the extent such disclosure is not inconsistent with this invention and for all jurisdictions in which such incorporation is permitted.

While the present invention has been described and illustrated by reference to particular embodiments, it will be appreciated by those of ordinary skill in the art that the invention lends itself to many different variations not illustrated herein. For these reasons, then, reference should be made solely to the appended claims for purposes of determining the true scope of the present invention.

Although the appendant claims have single appendencies in accordance with U.S. patent practice, each of the features in any of the appendant dams can be combined with each of the features of other appendant claims or the main claim.