Work

Polymorphism in Cannabinol Piperazine Cocrystals: Structural, Morphological, and Energetic Perspectives

Year: 2025

Type: article

Abstract: Polymorphism remains a major challenge in the development of pharmaceutical solid products as even small changes in the crystal arrangement can influence key properties such as stability and solubility. In this study, we mechanochemically prepared a novel cannabinol piperazine cocrystal, which exists in three polymorphic forms. The formation of these polymorphs was systematically investigated by varying the solvents, temperature, and milling time during the ball mill experiments. Interestingly, the phenomenon of disappearing polymorphs was observed under repeated milling. To get insights into the polymorphic behavior and assess the relative stability of the forms, we analyzed their crystal structures, morphologies, and hydrogen bond motifs and performed particle energy calculations using density functional theory. The theoretical results show good correlation with the experimental data and provide valuable and deep insights into the polymorphic behavior and the disappearance of the metastable form. Overall, this work highlights the importance of integrating structural analysis with energetic evaluations to rationalize and predict polymorph stability and transformations.

Source: Crystal Growth & Design

DOI: 10.1021/acs.cgd.5c01390

Authors: Adéla Koryt’áková, Argyro Chatziadi, Jan Rohlíček, Eliška Zmeškalová, Josef Beránek, Miroslav Šoóš

Institutions: University of Chemistry and Technology, Prague, Czech Academy of Sciences, FZU - Institute of Physics of the Czech Academy of Sciences

Language: English

Topic: Crystallization and Solubility Studies

Subfield: Materials Chemistry

Field: Materials Science

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funders: European Commission, Ministerstvo Školství, Mládeže a Tělovýchovy, Akademie Věd České Republiky, Agentura Pro Zdravotnický Výzkum České Republiky