TY - JOUR
T1 - Crystal structural analysis of dl-mandelate salt of carvedilol and its correlation with physicochemical properties
AU - Hata, Nanami
AU - Furuishi, Takayuki
AU - Tamboli, Majid I.
AU - Ishizaki, Momiji
AU - Umeda, Daiki
AU - Fukuzawa, Kaori
AU - Yonemochi, Etsuo
N1 - Funding Information:
Author Contributions: Conceptualization, N.H. and T.F.; formal analysis, N.H. and D.U.; investigation, N.H., EM.Y.I.;. vanisdu aDli.zUa.t;iwonr,itNin.gH o.,fTo.Fri.g, iMna.Il. Td.raanftdpDre.pUa.r;astuiopne,rvNis.Hio.n, ,TK.F..F,.aanndd ME..YI..T; .p; rworjeitcitnagd omf irneivsiterwat iaonnd, Te.dF.itainngd, ET..YF..;, K.F. and E.Y.; visualization, N.H., T.F., M.I.T. and D.U.; supervision, K.F. and E.Y.; project administration, T.F. the manuscript. and E.Y.; N.H. and T.F. contributed equally to this article. Funding: This study was supported by Hoshi University Grant-in-Aid for Leading Research Project grants in Funding: This study was supported by Hoshi University Grant-in-Aid for Leading Research Project grants in 2017 and 2018, and by the OTC Self-Medication Promotion Foundation 2018 (to T.F.). Acknowledgments: The authors thank Nao Kobayashi for the technical assistance provided in the eAxcpkenriomwelnetdagl mwoenrktss:. The authors thank Ms. Nao Kobayashi for the technical assistance provided in the
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/1/20
Y1 - 2020/1/20
N2 - A 1:1 salt of carvedilol (CVD), an anti-hypertensive drug, with DL-mandelic acid (DL-MA) was crystallized from ethanol and the structure was characterized by X-ray single-crystal diffraction, revealing salt formation by transfer of an acidic proton from the COOH group of MA to the aliphatic (acyclic) secondary amino NH group of CVD. The crystal structure is triclinic, with a P-1 space group and unit cell parameters a = 9.8416(5) Å, b = 11.4689(5) Å, c = 14.0746(7) Å, α = 108.595(8), β = 95.182(7), γ = 107.323(8), V = 1406.95(15) Å3, and Z = 2. The asymmetric unit contained one protonated CVD and one MA anion, linked via an N+ –H···O¯ strong hydrogen bond and a ratio of 1:1. As previously reported, the thermal, spectroscopic, and powder X-ray diffraction properties of the salt of CVD with DL-MA (CVD_DL-MA) differed from CVD alone. The intrinsic dissolution rate of CVD_DL-MA was about 10.7 times faster than CVD alone in a pH 6.8 buffer.
AB - A 1:1 salt of carvedilol (CVD), an anti-hypertensive drug, with DL-mandelic acid (DL-MA) was crystallized from ethanol and the structure was characterized by X-ray single-crystal diffraction, revealing salt formation by transfer of an acidic proton from the COOH group of MA to the aliphatic (acyclic) secondary amino NH group of CVD. The crystal structure is triclinic, with a P-1 space group and unit cell parameters a = 9.8416(5) Å, b = 11.4689(5) Å, c = 14.0746(7) Å, α = 108.595(8), β = 95.182(7), γ = 107.323(8), V = 1406.95(15) Å3, and Z = 2. The asymmetric unit contained one protonated CVD and one MA anion, linked via an N+ –H···O¯ strong hydrogen bond and a ratio of 1:1. As previously reported, the thermal, spectroscopic, and powder X-ray diffraction properties of the salt of CVD with DL-MA (CVD_DL-MA) differed from CVD alone. The intrinsic dissolution rate of CVD_DL-MA was about 10.7 times faster than CVD alone in a pH 6.8 buffer.
KW - Carvedilol
KW - Crystal structure
KW - DL-mandelic acid
KW - Salt
KW - Solubility
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U2 - 10.3390/cryst10010053
DO - 10.3390/cryst10010053
M3 - Article
AN - SCOPUS:85084729566
SN - 2073-4352
VL - 10
JO - Crystals
JF - Crystals
IS - 1
M1 - 53
ER -