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Dissolution Profiles of Carbamazepine Cocrystals with Cis–Trans Isomeric Coformers

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Abstract

Purpose

The purpose of the present study was to investigate the dissolution profiles of cocrystals with cis–trans isomeric coformers. Previously, the carbamazepine (CBZ) cocrystals with even-carbon dicarboxylic acids showed higher supersaturation than those with odd-carbon ones, attributed to particle surface solution-mediated phase transformation (PS-SMPT) to CBZ dihydrate (CBZ DH). However, it has been unknown whether this odd–even pattern holds for cis–trans isomeric coformers.

Method

CBZ cocrystals with maleic acid (MLE) and fumaric acid (FUM) (CBZ-FUM anhydrate (CBZ-FUM AH) and monohydrate (CBZ-FUM H2O)) were employed as model cocrystals. Hydroxypropyl　methylcellulose (HPMC), polyvinylpyrrolidone, and polyethylene glycol 6000 (PEG) were used as precipitation inhibitors. Dissolution tests were performed under a non-sink condition. Residual particles were analyzed by powder X-ray diffraction, differential scanning calorimetry, polarized light microscope, and scanning electron microscope.

Results

All cocrystals showed little supersaturation in the absence of a polymer. In 0.1% HPMC, CBZ-FUM AH showed significant supersaturation, whereas CBZ-MLE and CBZ-FUM H2O did not for the first two hours. HPMC reduced the initial dissolution rate of CBZ-MLE and CBZ-FUM H2O while inducing the highest supersaturation among the polymers after 96 h. The particle surface changed from a smooth plane to a striped pattern, but little or no CBZ DH was detected.

Conclusion

The cocrystals with cis–trans isomeric coformers showed different dissolution profiles. HPMC increased the dissolution rate of CBZ-FUM AH by inhibiting PS-SMPT but reduced the dissolution rate of CBZ-MLE and CBZ-FUM H2O without inducing PS-SMPT. The striped pattern was suggested to be due to surface etching rather than PS-SMPT.

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Data Availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Acknowledgements and Disclosures

The Author(s) declare(s) that they have no conflicts of interest to disclose.

Funding

This research was partly supported by AMED (Grant Number: JP17ak0101074).

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Authors and Affiliations

  1. Molecular Pharmaceutics Lab, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1, Noji-higashi, Kusatsu, Shiga, 525-8577, Japan

    Maaya Omori, Hibiki Yamamoto, Fumiya Matsui & Kiyohiko Sugano

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  1. Maaya Omori
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  2. Hibiki Yamamoto
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  3. Fumiya Matsui
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  4. Kiyohiko Sugano
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Contributions

Maaya Omori: Data acquisition, Data curation, Study design, Writing.

Hibiki Yamamoto: Data acquisition, Data curation.

Fumiya Matsui: Data acquisition, Data curation.

Kiyohiko Sugano: Study design, Supervision, Funding acquisition, Writing.

Corresponding author

Correspondence to Kiyohiko Sugano.

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Omori, M., Yamamoto, H., Matsui, F. et al. Dissolution Profiles of Carbamazepine Cocrystals with Cis–Trans Isomeric Coformers. Pharm Res 40, 579–591 (2023). https://doi.org/10.1007/s11095-022-03209-x

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  • DOI: https://doi.org/10.1007/s11095-022-03209-x

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