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Brexpiprazole-Catechol Cocrystal: Structure Elucidation, Excipient Compatibility and Stability


Brexpiprazole (BREX) is a well known drug used in the treatment of atypical psychotic disorder. BREX is known to exhibit photo instability on granulation with the most commonly used binder, Polyvinylpyrrolidone (PVP), in wet granulation. The present study reports the cocrystal of BREX with catechol (CAT), its structure elucidation using single crystal X-ray diffraction and its processability. Brexpiprazole catechol cocrystal (BRC) crystallizes in P21/c space group. Structural analysis of BRC shows R22(8) between BREX and CAT through weak C−H•••O and strong O−H•••O hydrogen bond interactions. BREX is marketed in tablet dosage form. Compatibility of generated cocrystal in the presence of several excipients was evaluated using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Cocrystal remained stable, with no signs of incompatibility during excipient compatibility study. Additionally, cocrystal and plain BREX granulated with PVP as a binder and chemical stability of the granules was investigated. Plain BREX showed oxidative degradation and formation of n-oxide degradation product under stability conditions within 7 days. More importantly, BRC displayed superior stability against stability conditions because the reactive site in piperazine ring of BREX moiety was blocked in BRC due to hydrogen bond between drug and co-former.

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Publication details

The article was received on 30 Jul 2019, accepted on 03 Oct 2019 and first published on 07 Oct 2019

Article type: Communication
DOI: 10.1039/C9CE01182J
CrystEngComm, 2019, Accepted Manuscript

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    Brexpiprazole-Catechol Cocrystal: Structure Elucidation, Excipient Compatibility and Stability

    M. R. Arabiani, K. Bal Raju, S. Bhunia, P. K. Teja, A. Lodagekar, R. B. Chavan, N. R. Shastri, C. M. Reddy, P. Shelat and D. Dave, CrystEngComm, 2019, Accepted Manuscript , DOI: 10.1039/C9CE01182J

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