May 18, 2021
Naír Rodriguez-Hornedo, PhD, professor of Pharmaceutical Sciences, and collaborators were recognized by the European Journal of Pharmaceutical Sciences.

See the original release on the European Journal of Pharmaceutical Sciences' website.

The European Journal of Pharmaceutical Sciences is delighted to announce the winner of the EJPS 2020 Best Paper Award. The winning paper has been selected by the EJPS award committee and will be presented at the next EUFEPS Annual Meeting

The role of pH and dose/solubility ratio on cocrystal dissolution, drug supersaturation and precipitation
Tatiane Cogo Machado, Gislaine Kuminek, Simone Gonçalves Cardoso, Naír Rodríguez-Hornedo
Volume 152, 1 September 2020

This article is freely available online for the next 6 months (until 30 November 2021).

This article explains how the integration of thermodynamic, kinetic, and biopharmaceutical properties of cocrystals provides a conceptual framework to understand cocrystal dissolution, drug supersaturation and precipitation (DSP) behavior. Cocrystal dissolution studies generally compare several cocrystals and their drug concentration-time profiles. However, the influence of drug dose and solubility has been scarcely reported. Unlike traditional supersaturating drug delivery systems, cocrystal stoichiometric composition provides unique control over cocrystal solubility and supersaturation with respect to drug. This article demonstrates that drug dose/solubility ratio (Do=Cdose/Sdrug) and cocrystal solubility advantage over drug (SA=Scocrystal/Sdrug) are essential parameters to classify cocrystals and interpret their dissolution profiles. This is shown to be critical when comparing cocrystal dissolution in different dissolution media and with different doses. Do varies with dose and drug solubility. It is a measure of the SA necessary to dissolve the dose. SA is proportional to the free energy for drug nucleation and its value represents the cocrystal potential for conversion to the less soluble drug. It is modulated by cocrystal and drug solubilities, ionization and solubilization by physiologically relevant surfactants. Drug release profiles for cocrystals of meloxicam show that maximum supersaturation (σmax=Cmax/Sdrug) and AUCdiss increase with increasing Do as pH decreases. When Do>>SA, the cocrystal solubility is not sufficient to dissolve the dose so that a dissolution-precipitation quasi-equilibrium state is able to sustain supersaturation. When Do<<SA, cocrystal solubility is more than adequate to dissolve the dose. Low σmax values near the value of Do were observed, where a large fraction of the cocrystal added is dissolved to reach σmax. The framework presented here provides a means to capitalize on the enhanced solubilities of cocrystals in the context of drug absorption properties.

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Tatiane Cogo Machado Gislaine Kuminek   Simone Gonçalves Cardoso Naír Rodríguez-Hornedo

Prof. Rodríguez-Hornedo’s research group at the University of Michigan, Department of Pharmaceutical Sciences, focuses on the underlying mechanisms and applications of pharmaceutical cocrystals, their design, synthesis, formulation, and performance. One of the main goals is to develop novel and efficient strategies to enhance the delivery of water insoluble drugs based on the solid and solution chemistry control that cocrystals provide. Pharmaceutical cocrystal engineering is a recent interdisciplinary field that applies concepts of supramolecular chemistry to design multiple component crystals via non-covalent interactions. However, as with other new technologies, there must be a conceptual framework to rationalize cocrystal properties and bio-performance, before one can confidently apply cocrystal technologies for drug delivery purposes. The central hypothesis of her research is that quantitative, mechanistic-based approaches can be developed to fine-tune cocrystal solid and solution properties, with huge implications for improving solubility, stability, and bio-performance.

In collaboration with Prof. Gonçalves Cardoso’s research group at the Universidade Federal de Santa Catarina, Brazil, Programa de Pós-Graduação em Fármacia, they have developed a conceptual framework for designing supersaturating cocrystal delivery systems where a target drug concentration can be achieved through the rational use of thermodynamic properties in combination with cocrystal dissolution/drug precipitation kinetics and oral absorption properties. With this foundation, the process of developing cocrystals, from solid form selection to engineered formulations, is expected to improve cocrystal dosage form performance and significantly increase the number of pharmaceutical products using this technology to address new therapies.

See the original release on the European Journal of Pharmaceutical Sciences' website.