Determination of Equilibrium Solubility and Octanol-Water Partition Coefficient of α-asaronol

Yitong Gong; Qunzheng Zhang; Yuhao Zhou; Yajun Bai; Xiaohui Zheng

doi:10.54691/5af4js53

Authors

Yitong Gong
Qunzheng Zhang
Yuhao Zhou
Yajun Bai
Xiaohui Zheng

DOI:

https://doi.org/10.54691/5af4js53

Keywords:

α-asaronol; High Performance Liquid Chromatography Method; uv Spectrophotometry; Equilibrium Solubility; Octanol-water Partition Coefficient.

Abstract

Objective: The objective of this study was to ascertain the equilibrium solubility and oil-water partition coefficient (lgP) of α-fine-octanol in disparate media, thereby establishing a theoretical foundation for the examination of α-fine-octanol formulations and pharmaceuticals. Methods: The equilibrium solubility and oil-water partition coefficient of α-asaronol were measured using UV spectrophotometry and high-performance liquid chromatography (HPLC). The lgP of α-asaronol was determined using the shake flask method. Results: The equilibrium solubility of α-fine-octanol at 37°C in four aqueous media, namely, distilled water, saline, phosphate buffer solution (pH 6.8 PBS), and pH 7.4 PBS, was 6090.3, 5361.8, 6300.7, and 5260.3 μg/mL, respectively. The equilibrium solubility of α-fine-octanol in the oil-phase medium, soybean oil, was found to be 8225.4 μg/mL, which is greater than the equilibrium solubility of α-fine-octanol in the oil-phase medium, soybean oil, and the equilibrium solubility of α-fine-octanol in the oil-phase medium, soybean oil. Additionally, the octanol-water partition coefficient (lgP) of α-asaronol in these four aqueous media at 37°C ranged from 1 to 2. Conclusion: α-asaronol exhibits slight solubility in distilled water, physiological saline, pH 6.8 PBS, pH 7.4 PBS and soybean oil. It is a fat-soluble API with adequate water solubility and is classified as a highly transmissible drug. This characteristic renders it suitable for the development and utilization in the formulation of dosage forms intended for oral and rectal administration.

Downloads

Download data is not yet available.

References

[1] Feng Mingnan. Research on the Quality Standard and Stability of Anti-Epileptic Candidate Drug 93S (0/1) [D]. Xi'an: Xi'an University of Petroleum, 2022.

[2] Zheng Xiaohui, Bai Yajun, Qin Fanggang, et al., α-asaronol and its preparation method and application. 10692696.9 [P]. 2014-11-26.

[3] Cartus A T, Dieter S. Metabolism of the carcinogen alpha-asarone in liver microsomes[J]. Food and Chemical Toxicology, 2015, 87(9): 103~112.

[4] Zhao Shizheng. Animal experiments on the anti-micro-pain effect of α-asaronol and exploration of its mechanism [J]. Journal of Integrated Traditional and Western Medicine, 1984, 4(8): 490-490.

[5] Hu Jinguan, Gu Jian, Wang Zhiwang. Experimental study on the effects of Acorus tatarinowii and its active components on the central nervous system [J]. Pharmacology and Clinical of Chinese Materia Medica, 1999, 15(3): 19-21.

[6] Zhou Daxing, Bao Zuxiao, Wu Xiongsheng. Anticonvulsant effect of the ethanol extract of Acorus tatarinowii [J]. Chinese Journal of Modern Applied Pharmacy, 1999, 16(5): 641-642.

[7] Zeng Min. Metabolism of the anti-epileptic active substance α-asaronol in normal and epileptic model rats [D]. Xi'an: Northwest University, 2017.

[8] Qin Fanggang. Design, synthesis, and anti-epileptic activity study of α-asaronol and its derivatives [D]. Xi'an: Northwest University, 2015.

[9] Benjamin D, Dickson. Synthesis of 2,3-syn-diarylpent-4-enamides via acyl-Claisen rearrangements of substituted cinnamyl morpholines: application to the synthesis of magnosalicin[J]. Tetrahedron Letters, 2012, 53(33):4464~4468.

[10] Zheng Xiaohui, Bai Yajun, Qin Fanggang, et al. α-asaronol and its preparation method and application [P]. CN: 104529724 A, 2015.04.22.

[11] Zhang Qunzheng, Wang Shichang, Ke Congyu, et al. Synthesis method of α-asaronol acetate and α-asaronol [P]. CN: 113387804 A, 2021.09.14.

[12] Han Yan, Chen Boying, Su Na, et al. Determination of the equilibrium solubility and apparent oil-water partition coefficient of Ambroxol Hydrochloride [J]. Journal of Drug Evaluation, 2016, 39(4): 615.

[13] Zhou Yuhao. Research on the formulation process and quality standard of α-asaronol preparations [D]. Xi'an: Xi'an University of Petroleum, 2023.

[14] FALLER B, ERTL P. Computational approaches to determine drug solubility[J]. Advanced Drug Delivery Reviews, 2007, 59(07): 533~545.

[15] New R R C, Kirby C J. Solubilisation of hydrophilic drugs in oily formulations[J]. Advanced Drug Delivery Reviews, 1997, 25: 59~69.

[16] Tamilvanan S. Oil-in-water lipid emulsions: implications for parenteral and ocular delivering systems[J]. Progress in Lipid Research, 2004, 43: 489~533.

[17] Wang Xue, Chen Hua, Yin Jie, et al. Determination of the equilibrium solubility and oil-water partition coefficient of Codeine Phosphate [J]. Journal of Pharmaceutical Analysis, 2019, 39(4): 749-754.

[18] Qian Guiying, Geng Liuqing, Shan Jinjun, et al. Determination of the physicochemical constants of total coumarins from Zishimai [J]. Journal of Information on Traditional Chinese Medicine, 2006, 13(10): 52-53.

[19] Zhang Minmin, Liu Chong, Chen Wen, et al. Determination of the equilibrium solubility, oil-water partition coefficient, and dissociation constant of Acacetin [J]. Shijizhen National Medicine and Pharmacy, 2020, 31(5): 1087.

[20] Zhu Rongyue, Chang Daoxiao, Sui Hong, et al. Determination of the equilibrium solubility and apparent oil-water partition coefficient of Lutein by HPLC [J]. Journal of Pharmaceutical Research, 2018, 37(7): 388.

[21] Zhang Huihui, Shi Yang, Zhang Xiaoxia, et al. Determination of the equilibrium solubility and oil-water partition coefficient of Punicalagin [J]. Journal of Xinjiang Medical University, 2018, 41(2): 225.