title: The delivery of arbidol by salt engineering: synthesis, physicochemical properties and pharmacokinetics.
abstract: The aim of the present study was to evaluate the feasibility of using the methanesulfonic salt of arbidol in order to improve its aqueous solubility and thus oral bioavailability. Arbidol mesylate (AM) was synthesized and then characterized using nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), and its apparent solubility and octanol-water partition coefficient were also studied. The results of NMR, IR, PXRD, SEM and DSC tests confirmed the salt formation. The apparent solubility of AM in water was 32-fold higher than that of the commercial product. A superior pH-dependent profile and an improved dissolution rate of AM were obtained in a variety of solutions with different pH values. In addition, AM exhibited a relatively higher peak plasma concentration (1460 versus 1297 ng/mL) and an increased AUC0-t(2475 versus 1277 ng/mL × h) when comparing with the commercial product, indicating the improved bioavailability of the drug. This study suggests that AM may be able to improve the therapeutic efficacy of arbidol, which rendering it to be a promising candidate for further development.
authors.affiliation: a Department of Pharmaceutical Analysis, School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Li
authors.affiliation: a Department of Pharmaceutical Analysis, School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Department of Pharmaceutical Analysis, School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Qikun
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: b Clinical Medical College of China Medical University , Shenyang , China.
authors.forename: Fangda
authors.initials: F
authors.lastname: Chi
authors.affiliation: a Department of Pharmaceutical Analysis, School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: a Department of Pharmaceutical Analysis, School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002616:Chemical Engineering / Q000379:methods*; D055598:Chemical Phenomena; D016503:Drug Delivery Systems / Q000379:methods*; D007211:Indoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D008297:Male; D008698:Mesylates / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014961:X-Ray Diffraction; D013440:Sulfides
chemical_list: D007211:Indoles; D008698:Mesylates; C086979:umifenovir; D013440:Sulfides
keywords: Arbidol mesylate; arbidol hydrochloride monohydrate; dissolution; pharmacokinetics; physicochemical properties; salt engineering