title: [Preparation and evaluation of intra-articular injectable sinomenine hydrochloride-loaded in situ liquid crystals].
abstract: Phytantriol (PT), ethanol (ET) and water were used to prepare in situ cubic liquid crystal (ISV2). The pseudo-ternary phase diagram of PT-ET-water was constructed and isotropic solution formulations were chosen for further optimization. The physicochemical properties of isotropic solution formulations were evaluated to optimize the composition of ISV2. In situ hexagonal liquid crystals (ISH2) were prepared based on the composition of ISV2 with the addition of vitamin E acetate (VitEA) and the amount of VitEA was optimized by in vitro release behavior. The phase structures of liquid crystalline gels formed by ISV2 and ISH2 in excess water were confirmed by crossed polarized light microscopy and small angle X-ray scattering, respectively. Rheological properties of ISV2 and ISH2 were studied by a DHR-2 rheometer. In vitro drug release studies were conducted by using a dialysis membrane diffusion method. Pharmacokinetics was investigated by determination of sinomenine hydrochloride (SMH) concentration in synovial membrane after intra-articular injection of SMH-loaded ISH2 in adjuvant-induced arthritis rats. The optimal ISV2 (PT/ET/water, 64 : 16 : 20, w/w/w) loaded with 6 mg x g(-1) of SMH showed a suitable pH, injectable and formed a cubic liquid crystalline gel in situ with minimum water absorption in the shortest time. The optimal ISV2 was able to sustain the drug release for 144 h. The optimal ISH2 system was prepared by addition of 5% VitEA into PT in the optimal ISV2 system. This ISH2 (PT/VitEA/ET/water, 60.8 : 3.2 : 16 : 20, w/w/w/w) was an injectable isotropic solution with suitable pH. The new ISH2 was able to sustain the drug release for more than 240 h. Local pharmacokinetics study indicated that the retention time and AUC(0-∞) of ISH2 group were increased significantly compared with that of SMH solution group and the AUC(0-∞) of ISH2 group was 6.01 times higher than that of SMH solution group. The developed ISH2 was suitable for intra-articular injection that may apply to patients in the treatment of rheumatoid arthritis.
authors.forename: Yu-lin
authors.initials: YL
authors.lastname: Chen
authors.forename: Shuang-ying
authors.initials: SY
authors.lastname: Gui
authors.forename: Xin
authors.initials: X
authors.lastname: Liang
authors.forename: Sheng-mei
authors.initials: SM
authors.lastname: Wang
authors.forename: Xiao-jing
authors.initials: XJ
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D000431:Ethanol; D005233:Fatty Alcohols; D005782:Gels; D007270:Injections, Intra-Articular; D050866:Liquid Crystals; D009019:Morphinans / Q000008:administration & dosage* / Q000737:chemistry*; D051381:Rats; D012212:Rheology; D014867:Water; D024502:alpha-Tocopherol
chemical_list: D005233:Fatty Alcohols; D005782:Gels; D009019:Morphinans; D014867:Water; D000431:Ethanol; C009271:sinomenine; C508873:3,7,11,15-tetramethyl-1,2,3-hexadecanetriol; D024502:alpha-Tocopherol