OBJECTIVE To prepare a novel naringenin co-crystal to improve the poor water solubility of the compound. METHODS Solvent volatilization method was used to prepare naringenin nicotinamide co-crystal, with ethyl acetate as solvent. It is characterized by the technology of infrared spectroscopy (IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), scanning electron microscopy (SEM) and other techniques. RESULTS By measuring the equilibrium solubility of different pH solutions, it was found that the naringenin nicotinamide co-crystal has a significantly improved equilibrium solubility compared with naringenin. CONCLUSION This method can improve the solubility of naringenin, which is simple and easy, and lays the foundation for further study of naringenin co-crystal.
XU Dan, LI Tong, ZHANG Ting-ting, JIN Bo, MA Chen.
Preparation and Characterization of Naringenin Nicotinamide Co-crystal[J]. Chinese Pharmaceutical Journal, 2019, 54(4): 291-296 https://doi.org/10.11669/cpj.2019.04.007
[1] PARK M, KIM K, LEE Y M, et al. Naringenin stimulates cholecystokinin secretion in STC-1 cells. Nutr Res Pract, 2014, 8(2):146-150. [2] CAVIA-SAIZ M, BUSTO M D, PILAR-IZQUIERDO M C, et al. Antioxidant properties, radical scavenging activity and biomolecule protection capacity of flavonoid naringenin and its glycoside naringin: a comparative study . J Sci Food Agric, 2010, 90(7):1238-1244. [3] LIM W, PARK S, BAZER F W, et al. Naringenin-induced apoptotic cell death in prostate cancer cells is mediated via the PI3K/AKT and MAPK signaling pathways . J Cell Biochem, 2017, 118(5):1118-1131. [4] PARK H J, CHOI Y J, LEE J H, et al. Naringenin causes ASK1-induced apoptosis via reactive oxygen species in human pancreatic cancer cells. Food Chem Toxicol, 2017, 99:1-8. [5] ANDERSON W, BARROWS M, LOPEZ F, et al. Investigation of the anxiolytic effects of naringenin, a component of mentha aquatica, in the male Sprague-Dawley rat. Holist Nurs Pract, 2012, 26(1):52-57. [6] MANCHOPE M F, CASAGRANDE R, VERRI W A J R. Naringenin: an analgesic and anti-inflammatory citrus flavanone. Oncotarget, 2017, 8(3):3766-3767. [7] JIN L, ZENG W, ZHANG F, et al. Naringenin ameliorates acute inflammation by regulating intracellular cytokine degradation. J Immunol, 2017, 199(10):3466-3477. [8] NYANE N A, TLAILA T B, MALEFANE T G, et al. Metformin-like antidiabetic, cardio-protective and non-glycemic effects of naringenin: molecular and pharmacological insights. Eur J Pharmacol, 2017, 803:103-111. [9] SANDEEP M S, NANDINI C D. Influence of quercetin, naringenin and berberine on glucose transporters and insulin signalling molecules in brain of streptozotocin-induced diabetic rats. Biomed Pharmacother, 2017, 94:605-611. [10] ZHANG T T, MA C. Determination of plasma concentration of naringenin and glucuronic acid conjugate in rat plasma by high performance liquid chromatography-tandem mass spectrometry. Chin Pharm J(中国药学杂志), 2014, 49(10):864-868. [11] MA Y, LIN B Q, LI W Z, et al. Study on the absorption kinetics of naringenin in the intestine. Chin Tradit Patent Med(中成药), 2012, 34(8):1487-1491. [12] HSIU S L, HUANG T Y, HOU Y C, et al. Comparison of metabolic pharmacokinetics of naringin and naringenin in rabbits. Life Sci,2002, 70 (13):1481-1489. [13] KHAN A W, KOTTA S, ANSARI S H, et al. Enhanced dissolution and bioavailability of grapefruit flavonoid naringenin by solid dispersion utilizing fourth generation carrier. Drug Dev Ind Pharm, 2015, 41(5):772-779. [14] SINGH M K, POOJA D, RAVURI H G, et al. Fabrication of surfactant-stabilized nanosuspension of naringenin to surpass its poor physiochemical properties and low oral bioavailability. Phytomedicine, 2018, 40:48-54. [15] GERA S, TALLURI S, RANGARAJ N, et al. Formulation and evaluation of naringenin nanosuspensions for bioavailability enhancement. AAPS Pharm Sci Tech, 2017, 18(8):3151-3162. [16] JI P, ZHAO W M. Preparation of naringenin liposome and pharmacokinetic study of rat lung administration. Chin Tradit Pat Med(中成药), 2015,37(8):1699-1704. [17] JI P, ZHAO W M. Preparation and pharmacodynamic evaluation of naringenin liposome freeze-dried powder. Acta Acad Med Sin(中国医学科学院学报), 2015,37(2):208-214. [18] GAO Y, ZU H, ZHANG J J. Pharmaceutical cocrystals. Prog Chem(化学进展), 2010, 22(5):829-835. [19] YADAV A V, SHETE A S, DABKE A P, et al. Co-crystals: a novel approach to modify physicochemical properties of active pharmaceutical ingredients . Indian J Pharm Sci, 2009,71(4):359-370. [20] MIROSHNYK I, MIRZA S, SANDLER N. Pharmaceutical co-crystals-an opportunity for drug product enhancement . Expert Opin Drug Deliv, 2009, 6(4):333-341. [21] YI H, YIN Y M, ZHAO X L, et al. Preparation and characterization of itraconazole eutectic. J Shenyang Pharm Univ(沈阳药科大学学报), 2014,31(3):161-168. [22] XU H, ZHANG F K, CHI Z L, et al. Preparation of curcumin lysine eutectic and comparison of solubility of different crystal forms. Chin Pharm(中国药师),2017,20(2):208-212. [23] LIANG S J, ZHOU S Y, YANG S T, et al. Thermodynamic study on the formation of naringenin-isonicotinamide eutectic. Acta Pharm Sin(药学学报), 2017,52(4):625-633. [24] LIANG W D, LUO C, ZAHNG H L, et al. Characterization and properties of isoniazid-naringenin eutectic. J Wuhan Univ Sci Technol(武汉科技大学学报), 2018, 41(3):190-194. [25] HUANG T, LIN X R. Progress in the application of nicotinamide in dermatology. Int J Dermatol Venereol(国际皮肤性病学杂志), 2009,35(2):76-79. [26] FDA. Guidance for industry: Regulatory classification of pharmaceutical co-crystals . FDA,[2011-12-01] [2013]. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. [27] JOVANOVIC S V, STEENKEN S, TOSIC M, et al. Flavonoids as antioxidants. J Am Chem Soc,1994, 116(11):4846-4851. [28] SHI Y, FRITZ J S. New electrolyte systems for the determination of metal cations by capillary zone electrophoresis. J Chromatogr A, 1994, 671(1-2):429-435. [29] JEON S H, CHUN W, CHOI Y J, et al. Cytotoxic constituents from the bark of Salix Hulteni. Arch Pharm Res, 2008, 31(8):978-982.