Active Pharmaceutical Ingredients (APIs) such as praziquantel, nitazoxanide, and other imidazol-related APIs are among the most widely prescribed compounds to treat diseases caused by protozoa and parasitic worms (helmints). These active molecules are also found among the so-called �brick dust� type due to their low intrinsic solubility, limitation that generally leads to the high-dose employed during their administration in oral formulations. Strategies to improve solubility and dissolution rates of pharmaceutical solids explore new polymorphs, solvates, or salts. Recently, cocrystals have found acceptance in both industry and academia as useful alternatives to overcome these limitations. Herein, we present the supramolecular design, screening and synthesis of several new cocrystals obtained from praziquantel (a potent anthelmintic that does not contain any salt-forming functional group), nitazoxanide (a nitro-imidazole) and other benzimidazol related APIs, in combination with carboxylic acid derivatives as cocrystal formers. These solid-state forms were synthesized mainly by three methodologies: crystallization from saturated solutions, solid-solid phase transformation, and grinding. Solids were characterized by means of X-ray diffraction (powder and single-crystal), solid state NMR (CP-MAS), FTIR and thermal analyses. Measurements of solubility and dissolution rates afforded from small (2x) to large (30x) increases in comparison to the parent reference compounds. Our studies demonstrate the variety of solid-state phases that can be obtained via cocrystallization, displaying in many instances a favorable biopharmaceutical performance.

From �brick dust� APIs to new solid phases: Biopharmaceutical improvement through cocrystallization

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.