title: Physicochemical characterization and an injection formulation study of water insoluble ZCVI₄-2, a novel NO-donor anticancer compound.
abstract: ZCVI(4)-2 was a novel nitric oxide-releasing glycosyl derivative of oleanolic acid that displayed strong cytotoxicity selectively against human hepatocellular carcinoma in vitro and in vivo. In this study, ZCVI(4)-2 was characterized by FT-IR spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, Raman spectroscopy, hygroscopicity and stability. A high performance liquid chromatography method was also established for the quantitative determination of solubility and additional stability profile of ZCVI(4)-2. ZCVI(4)-2 was found to be an amorphous and stable solid with low solubility of less than 10 μg/mL. Based on the solubilization tests that included methods of cosolvency and micellization, the solution mixture of 5% Solutol HS-15, 5% 1, 2-propylene glycol and 5% anhydrous ethanol was determined to be the system for the preparation of the ZCVI(4)-2 early injection solution. The effect of pH, temperature, light and injectable isotonic glucose or NaCl solution on ZCVI(4)-2 injection was also investigated. Good stability was observed at all testing conditions. Under the conditions studied, the NO-releasing rate and amount of ZCVI(4)-2 from the early injection solution in rat plasma demonstrated a promising therapeutic efficacy while maintaining a good safety profile.
authors.affiliation: School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Su
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Gong
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Lai
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D000431:Ethanol / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007267:Injections; D007552:Isotonic Solutions; D008027:Light; D008297:Male; D008956:Models, Chemical; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry*; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D033362:Powder Diffraction; D011409:Propylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013229:Stearic Acids / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D014867:Water / Q000737:chemistry*; D017155:Wettability
chemical_list: D000970:Antineoplastic Agents; D007552:Isotonic Solutions; D020030:Nitric Oxide Donors; D011108:Polymers; D011409:Propylene Glycols; D012997:Solvents; D013229:Stearic Acids; C561136:ZCVI4-2; D014867:Water; C012504:polypropylene glycol; D000431:Ethanol; D011092:Polyethylene Glycols; D012965:Sodium Chloride; C067028:Solutol HS 15; D009828:Oleanolic Acid; D005947:Glucose