Zhang Xitong, Zhang Yue, Han Han, Yang Jun, Xu Benliang, Wang Bing, Zhang Tong
Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine.
Shanghai Xiangshan Hospital of Traditional Chinese Medicine.
Chem Pharm Bull (Tokyo). 2017 Aug 1;65(8):706-713. doi: 10.1248/cpb.c16-00993. Epub 2017 May 19.
This study aims to develop a gastroretentive sustained-release drug delivery system of paeonol using floating properties and to investigate its therapeutic effects in rat models. The gastric retention tablets of paeonol (GRT-Ps) were prepared by a direct compression method, and the Box-Behnken design was used to optimize its formulation. The optimized formulation containing 15% NaHCO and a 2 : 1 ratio of paeonol and HPMC-K4M floated within 1 min and remained afloat for more than 8 h in the simulated gastric fluid (200 mL, pH=1.2) and simultaneously showed the desired sustained drug release. Moreover, small tablets (3 mm) were prepared according to the same formulation and the process technology of big tablets (8 mm). A similar drug release behavior was observed between two kinds of tablets (f=52), and then the evaluations of efficacy and retention capacity in vivo were conducted with small tablets. In vivo retention studies showed that the T (2 h) of GRT-P in rat stomachs was significantly extended compared with the T (0.5 h) of normal reference preparation. Compared with the model group, low and high doses of GRT-P could significantly inhibit the increase of malondialdehyde (MDA) in serum. Studies showed that the higher MDA content in inflammation tissue increases the inflammatory response. The ulcer inhibition rates of GRT-P in the high-dose group were 59.0 and 64.1% in the ranitidine group. Results indicated that GRT-Ps had the potential for a sustained drug release and an enhanced gastric residence time with relatively high drug concentrations in the tissue distribution.
本研究旨在利用漂浮特性开发丹皮酚胃滞留缓释给药系统，并在大鼠模型中研究其治疗效果。采用直接压片法制备丹皮酚胃滞留片（GRT-Ps），并采用Box-Behnken设计优化其处方。优化后的处方含有15%的碳酸氢钠，丹皮酚与羟丙甲纤维素K4M的比例为2:1，在模拟胃液（200 mL，pH = 1.2）中1分钟内漂浮，并在8小时以上保持漂浮状态，同时呈现出理想的药物缓释效果。此外，按照相同的处方和大片剂（8 mm）的工艺技术制备了小片剂（3 mm）。两种片剂之间观察到相似的药物释放行为（f = 52），然后用小片剂进行体内疗效和滞留能力评估。体内滞留研究表明，与正常参比制剂的T（0.5小时）相比，GRT-P在大鼠胃中的T（2小时）显著延长。与模型组相比，低剂量和高剂量的GRT-P均可显著抑制血清中丙二醛（MDA）的升高。研究表明，炎症组织中较高的MDA含量会增加炎症反应。GRT-P高剂量组的溃疡抑制率在雷尼替丁组中分别为59.0%和64.1%。结果表明，GRT-Ps具有药物缓释和延长胃内滞留时间的潜力，在组织分布中具有相对较高的药物浓度。
