Song Yanqing, Gao Huan, Zhang Sixi, Zhang Yue, Jin Xiangqun, Sun Jingmeng
Department of Pharmaceutics, School of Pharmaceutical Sciences, Jilin University.
Department of Pharmacy, The First Hospital of Jilin University.
Biol Pharm Bull. 2017 Dec 1;40(12):2081-2087. doi: 10.1248/bpb.b17-00162. Epub 2017 Sep 23.
The purpose of this study is to develop a new method of preparing salvianolic acid extracts (SAE) water-in-oil-in-water (W/O/W) multiple emulsion (ME). SAE injection is used in the treatment of brain infarct and promotion of blood circulation in China. However, the injection is not convenient, and the oral preparation has poor bioavailability. Hence, a new preparation that is convenient and stable with good biological availability is required. SAE ME was prepared by two-step emulsification method. Combined with single-factor investigation and orthogonal test, the embedding rate and centrifugal retention rate were taken as the comprehensive indexes to optimize the formulation of SAE ME. The ME size was tested by laser particle size analyzer. The pharmacokinetic studies were conducted in Sprague-Dawley rats with HPLC-MS/MS method. The blood coagulation and hemorheology tests were conducted to assess the effect of preparation in rats. The best preparation technique for SAE ME is by the use of trospium chloride; SAE represent 12% of water in the phase, lipophilic emulsifier hydrophilic lipophilic balance value=4.3, lipophilic emulsifier is 20% of the oil phase. The median diameter of particle is (0.608±0.05) µm and the C of ME is 3-fold higher compared to C of free drug. The oral biavailability of ME is 26.71-fold higher than that of free drug with good effect on blood circulation. SAE ME is stable hence, improves the biological availability and slows down drug release.
本研究旨在开发一种制备丹酚酸提取物(SAE)水包油包水(W/O/W)多重乳液(ME)的新方法。在中国,SAE注射液用于治疗脑梗死和促进血液循环。然而,该注射液使用不便,口服制剂的生物利用度较差。因此,需要一种方便、稳定且具有良好生物利用度的新制剂。SAE多重乳液采用两步乳化法制备。结合单因素考察和正交试验,以包封率和离心保留率作为综合指标来优化SAE多重乳液的处方。通过激光粒度分析仪测定多重乳液的粒径。采用HPLC-MS/MS法在Sprague-Dawley大鼠中进行药代动力学研究。进行凝血和血液流变学试验以评估该制剂在大鼠中的效果。SAE多重乳液的最佳制备工艺是使用氯化托烷司琼;SAE在水相中占12%,亲脂性乳化剂的亲水亲油平衡值=4.3,亲脂性乳化剂占油相的20%。颗粒的中位直径为(0.608±0.05)µm,多重乳液的C值比游离药物的C值高3倍。多重乳液的口服生物利用度比游离药物高26.71倍,对血液循环有良好效果。SAE多重乳液稳定,因此提高了生物利用度并减缓了药物释放。