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Zwitterionic cocrystal of diclofenac and L-proline: Structure determination, solubility, kinetics of cocrystallization, and stability study
Nugrahani I.a, Utami D.a,c, Ibrahim S.a, Nugraha Y.P.b, Uekusa H.b
a School of Pharmacy, Bandung Institute of Technology, Bandung, 40132, Indonesia
b Department of Chemistry, School of Science, Tokyo Institute of Technology, Tokyo, 152-8550, Japan
c Faculty of Pharmacy, Ahmad Dahlan University, Yogyakarta, 55166, Indonesia
[vc_row][vc_column][vc_row_inner][vc_column_inner][vc_separator css=”.vc_custom_1624529070653{padding-top: 30px !important;padding-bottom: 30px !important;}”][/vc_column_inner][/vc_row_inner][vc_row_inner layout=”boxed”][vc_column_inner width=”3/4″ css=”.vc_custom_1624695412187{border-right-width: 1px !important;border-right-color: #dddddd !important;border-right-style: solid !important;border-radius: 1px !important;}”][vc_empty_space][megatron_heading title=”Abstract” size=”size-sm” text_align=”text-left”][vc_column_text]© 2018 Elsevier B.V.In recent decades, the design of cocrystals has developed significantly due to the unique characteristics and advantages of cocrystals, which help to improve the physicochemical properties of drugs, especially solubility. Zwitterions are attractive and interesting co-formers. However, the physicochemical properties of cocrystals with zwitterionic co-formers, i.e. zwitterionic cocrystals, have not been adequately evaluated. In this study, solid-state characterization of a newly developed zwitterionic cocrystal of diclofenac (DFA), a non-steroidal anti-inflammatory drug, and the amino acid L-proline (PRO) was performed using Fourier-transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction (PXRD) analyses. In addition, the crystal structure of the cocrystal (DFA-PRO) was determined by single-crystal X-ray diffraction analysis, after which the zwitterionic structure was confirmed. The cocrystallization during co-grinding, which was investigated by PXRD, followed first-order kinetics. Furthermore, the solubility of the zwitterionic cocrystals was 7.5-times higher than that of the DFA crystals. The results indicate that the cocrystal is stable under ambient conditions; however, it hydrates and transforms into a mixture of L-proline monohydrate crystals and DFA crystals under conditions of high humidity.[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Author keywords” size=”size-sm” text_align=”text-left”][vc_column_text]Anti-Inflammatory Agents, Non-Steroidal,Calorimetry, Differential Scanning,Crystallization,Diclofenac,Drug Stability,Kinetics,Molecular Structure,Powder Diffraction,Proline,Solubility,Spectroscopy, Fourier Transform Infrared,X-Ray Diffraction[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Indexed keywords” size=”size-sm” text_align=”text-left”][vc_column_text]Co-grinding,Cocrystal,Diclofenac,L-Proline,Solubility,Stability[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Funding details” size=”size-sm” text_align=”text-left”][vc_column_text]This research was supported by World Class University Program: International Research Collaboration between LPPM-ITB (Jawa Barat, Indonesia) with Department of Chemistry and Material Science, Tokyo Institute of Technology , Japan (grant number: 007/WCU-ITB/LL/III/2017 ).[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”DOI” size=”size-sm” text_align=”text-left”][vc_column_text]https://doi.org/10.1016/j.ejps.2018.02.020[/vc_column_text][/vc_column_inner][vc_column_inner width=”1/4″][vc_column_text]Widget Plumx[/vc_column_text][/vc_column_inner][/vc_row_inner][/vc_column][/vc_row][vc_row][vc_column][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][/vc_column][/vc_row]