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Recent Advances on the Biological Study of Pharmaceutical Cocrystals

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Abstract

As a low-risk, low-cost, but high-reward route, cocrystallization of drugs with appropriate coformers is applied to improve the physiochemical and biopharmaceutical properties of drugs. Currently, most researchers concentrate their efforts on the preparation, characterization, and improvement of physicochemical properties of pharmaceutical cocrystals. On the contrary, the biological study of pharmaceutical cocrystals has not attracted wide attention of researchers. In this review, we have focused on recent advances reporting the biological studies of pharmaceutical cocrystals. The covered areas consist of the solubility and permeability, the pharmacokinetics study, metabolism and distribution, pharmacodynamics research, and the toxicological evaluation of pharmaceutical cocrystals. Besides, discussions have been made on the in vivo–in vitro correlations for pharmaceutical cocrystals, the enhancement of efficiency and reduction of toxicity for pharmaceutical cocrystals, and the interaction between APIs and coformers in pharmaceutical cocrystals and marketed pharmaceutical cocrystals as well as their biological studies. At the same time, some problems such as the amount of animal samples, the number and distribution of blood sampling points, investigation on the pharmacokinetics of physical mixtures containing APIs and coformers, and the consideration of species differences should be taken into account. Although pharmaceutical cocrystals face some challenges in clarifying the characteristics of metabolism and distribution, revealing potential pharmacological mechanism, and evaluating safety, cocrystal engineering is still considered a green and promising approach to developing valuable new drugs.

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Funding

This work was financially supported by the CAMS Innovation Fund for Medical Sciences (CIFMS) (2021–1-I2M-029).

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Authors and Affiliations

  1. Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of China

    Zhipeng Wang, Mingchao Yu, Shiying Yang & Yang Lu

  2. Beijing City Key Laboratory of Drug Target and Screening Research, National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of China

    Yifei Xie & Guanhua Du

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  1. Zhipeng Wang
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  2. Yifei Xie
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  3. Mingchao Yu
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  4. Shiying Yang
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  5. Yang Lu
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  6. Guanhua Du
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Contributions

Conceptualization: Zhipeng Wang, Shiying Yang, Yang Lu, and Guanhua Du; writing—original draft preparation: Zhipeng Wang; literature review and collection: Yifei Xie and Mingchao Yu; review and editing: Shiying Yang, Yang Lu, and Guanhua Du. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Shiying Yang, Yang Lu or Guanhua Du.

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Wang, Z., Xie, Y., Yu, M. et al. Recent Advances on the Biological Study of Pharmaceutical Cocrystals. AAPS PharmSciTech 23, 303 (2022). https://doi.org/10.1208/s12249-022-02451-1

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