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Salt cocrystal of diclofenac sodium-l-proline: Structural, pseudopolymorphism, and pharmaceutics performance study
Nugrahani I.a, Kumalasari R.A.a, Auli W.N.a, Horikawa A.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, 152-8551, Japan
[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]© 2020 by the authors. Licensee MDPI, Basel, Switzerland.Previously, we have reported on a zwitterionic cocrystal of diclofenac acid and L-proline. However, the solubility of this multicomponent crystal was still lower than that of diclofenac sodium salt. Therefore, this study aimed to observe whether a multicomponent crystal could be produced from diclofenac sodium hydrate with the same coformer, L-proline, which was expected to improve the pharmaceutics performance. Methods involved screening, solid phase characterization, structure determination, stability, and in vitro pharmaceutical performance tests. First, a phase diagram screen was carried out to identify the molar ratio of the multicomponent crystal formation. Next, the single crystals were prepared by slow evaporation under two conditions, which yielded two forms: one was a rod-shape and the second was a flat-square form. The characterization by infrared spectroscopy, thermal analysis, and diffractometry confirmed the formation of the new phases. Finally, structural determination using single crystal X-ray diffraction analysis solved the new salt cocrystals as a stable diclofenac–sodium–proline–water (1:1:1:4) named NDPT (natrium diclofenac proline tetrahydrate), and unstable diclofenac–sodium–proline–water (1:1:1:1), named NDPM (natrium diclofenac proline monohydrate). The solubility and dissolution rate of these multicomponent crystals were superior to those of diclofenac sodium alone. The experimental results that this salt cocrystal is suitable for further development.[/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][/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]Diclofenac sodium,Dissolution,L-proline,Monohydrate,Multicomponent crystal,Salt cocrystal,Solubility,Stability,Tetrahydrate[/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][{‘$’: ‘Acknowledgments: This research was funded by High Educational Directorate of Indonesia Education Ministry of Republic Indonesia—Research and Society Service Institution of Bandung Institute of Technology, Number 2/E1/KP.PTNBH/2020 (IN). A part of this study was performed in Tokyo Institute of Technology, Japan, and was supported by JSPS KAKENHI Grant Number JP18H04504 and 20H04661 (HU).’}, {‘$’: ‘Funding: This research was funded by High Educational Directorate of Indonesia Education Ministry of Republic Indonesia—Research and Society Service Institution of Bandung Institute of Technology, Number 2/E1/KP.PTNBH/2020 (IN). A part of this study was performed in Tokyo Institute of Technology, Japan, and was supported by JSPS KAKENHI Grant Number JP17K05745 and JP18H04504 (HU).’}, {‘$’: ‘This research was funded by High Educational Directorate of Indonesia Education Ministry of Republic Indonesia?Research and Society Service Institution of Bandung Institute of Technology, Number 2/E1/KP.PTNBH/2020 (IN). A part of this study was performed in Tokyo Institute of Technology, Japan, and was supported by JSPS KAKENHI Grant Number JP17K05745 and JP18H04504 (HU). This research was funded by High Educational Directorate of Indonesia Education Ministry of Republic Indonesia?Research and Society Service Institution of Bandung Institute of Technology, Number 2/E1/KP.PTNBH/2020 (IN). A part of this study was performed in Tokyo Institute of Technology, Japan, and was supported by JSPS KAKENHI Grant Number JP18H04504 and 20H04661 (HU).’}][/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/10.3390/pharmaceutics12070690[/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]