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Journal logoSTRUCTURAL
CHEMISTRY
ISSN: 2053-2296

Improving the solubility of berberine

aQuinta do Anjo, Portugal
*Correspondence e-mail: jafernandes1974@gmail.com

While a certain compound can be considered as an active pharmaceutical ingredient (API) in controlled situations, it may fail as a medicine due to problems related to its physical, chemical or biological properties. Moisture, heat or oxygen may jeopardize the chemical or physical stability of the compound, compromising its long-term storage. On the other hand, the form in which the compound is available may present poor solubility in water, preventing its absorption by the human body. The preparation of cocrystals is among the solutions that have been used to circumvent these kinds of problems. If one of the components of a cocrystal is an API, the crystal is classified as a pharmaceutical cocrystal. Conversely, the other component is called a coformer. It is the screening of the vast number of available coformers that allows the optimization of the target parameter (e.g. improving stability toward moisture).

In spite of berberine (BBR) being a water-soluble drug with a wide spectrum of medical applications, it presents poor intestine absorption via oral administration (Fratter & De Servi, 2014[Fratter, A. & De Servi, B. (2014). Int. J. Drug Deliv. Technol. 5, 33-42.]). Additionally, this API is highly hygroscopic and presents an extremely bitter taste. Cocrystals have been prepared in attempts to solve these problems (Lu et al., 2019[Lu, Q., Dun, J., Chen, J., Liu, S. & Sun, C. C. (2019). Int. J. Pharm. 554, 14-20.]; Wang et al., 2016[Wang, C., Perumalla, S. R., Lu, R., Fang, J. & Sun, C. C. (2016). Cryst. Growth Des. 16, 933-939.]).

Recently, in Acta Crystallographica Section C, Sun et al. (2019[Sun, W., Zuo, L., Zhao, T., Zhu, Z. & Shan, G. (2019). Acta Cryst. C75, 1644-1651.]) proposed a possible solution for improving the water solubility of BBR by the formation of multicomponent pharmaceutical salts (or ionic cocrystals in a wider definition; Kumar & Nanda, 2018[Kumar, S. & Nanda, A. (2018). Mol Cryst. Liq. Cryst. 667, 54-77.]) with diclofenac (DIC), another known API, as coformer. Thus, they managed to prepare DIC salts of BBR as a dihydrate (denoted I) and four other solvates [hemidi­chloro­methane dihydrate (II), ethanol (III) and methanol (IV and V, mono- and disolvates, respectively)]. These salts were readily prepared by slow evaporation of mixtures containing the corresponding solvents.

All crystals show an N—H⋯O hydrogen-bond inter­action between the amino group of DIC and the carboxyl­ate group of BBR comprising an S(7) graph-set motif. Additionally, O—H⋯O hydrogen-bond inter­actions are also present in I, II and V, comprising rings with R44(12) and R46(12) graph-set motifs in I, a one-dimensional chain in II and an isolated hydrogen bond in V. Additionally, ππ interactions are also present in all the compounds, except for II.

Sun et al. (2019[Sun, W., Zuo, L., Zhao, T., Zhu, Z. & Shan, G. (2019). Acta Cryst. C75, 1644-1651.]) have contributed to the library extension of berberine presentations. Further studies may result in the use of the prepared compounds for new formulations of berberine with improved properties.

References

First citationFratter, A. & De Servi, B. (2014). Int. J. Drug Deliv. Technol. 5, 33–42.  Google Scholar
First citationKumar, S. & Nanda, A. (2018). Mol Cryst. Liq. Cryst. 667, 54–77.  CrossRef CAS Google Scholar
First citationLu, Q., Dun, J., Chen, J., Liu, S. & Sun, C. C. (2019). Int. J. Pharm. 554, 14–20.  CSD CrossRef CAS PubMed Google Scholar
First citationSun, W., Zuo, L., Zhao, T., Zhu, Z. & Shan, G. (2019). Acta Cryst. C75, 1644–1651.  CSD CrossRef IUCr Journals Google Scholar
First citationWang, C., Perumalla, S. R., Lu, R., Fang, J. & Sun, C. C. (2016). Cryst. Growth Des. 16, 933–939.  Web of Science CSD CrossRef CAS Google Scholar

© International Union of Crystallography. Prior permission is not required to reproduce short quotations, tables and figures from this article, provided the original authors and source are cited. For more information, click here.

Journal logoSTRUCTURAL
CHEMISTRY
ISSN: 2053-2296
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