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新型罗望子多糖-海藻酸钠黏膜粘附微球用于口服格列齐特给药:体内外评价。

Novel tamarind seed polysaccharide-alginate mucoadhesive microspheres for oral gliclazide delivery: in vitro-in vivo evaluation.

机构信息

Faculty of Pharmacy, The University of Sydney, NSW, Australia.

出版信息

Drug Deliv. 2012 Apr;19(3):123-31. doi: 10.3109/10717544.2012.657717. Epub 2012 Feb 22.

DOI:10.3109/10717544.2012.657717
PMID:22352984
Abstract

Novel tamarind seed polysaccharide (TSP)-alginate mucoadhesive microspheres were prepared using TSP and alginate as blend in different ratios with different calcium chloride (CaCl(2)) concentration as a cross linker by ionotropic gelation. The prepared microspheres were of spherical shape having rough surfaces, and average particle sizes within the range of 752.12 ± 6.42 to 948.49 ± 20.92 µm. The drug entrapment efficiency of these microspheres were within the range between 58.12 ± 2.42 to 82.78 ± 3.43% w/w. Fourier transform infrared (FTIR) studies indicated that there were no reactions between gliclazide, and polymers (TSP, and sodium alginate) used. Different formulations of gliclazide loaded TSP-alginate microspheres showed prolonged in vitro release profiles of gliclazide over 12 hours in both stomach pH (pH 1.2), and intestinal pH (pH 7.4). It was found that the gliclazide release in gastric pH was comparatively slow and sustained than intestinal pH. These TSP-alginate microspheres also exhibited good mucoadhesivity. The in vivo studies on alloxan-induced diabetic rats (Animal Ethical Committee registration number: IFTM/837ac/0160) demonstrated the significant hypoglycemic effect of selected formulation of TSP-alginate mucoadhesive microspheres containing gliclazide on oral administration. This developed gliclazide loaded new TSP-alginate mucoadhesive microspheres may be very much useful for prolonged systemic absorption of gliclazide for proper maintaining blood glucose level and advanced patient compliance.

摘要

新型罗望子多糖(TSP)-海藻酸钠黏膜粘附微球是通过离子凝胶作用,以不同比例的 TSP 和海藻酸钠作为共混物,并以不同浓度的氯化钙(CaCl 2 )作为交联剂制备而成。所制备的微球呈球形,表面粗糙,平均粒径在 752.12±6.42 至 948.49±20.92μm 范围内。这些微球的药物包封效率在 58.12±2.42 至 82.78±3.43%w/w 之间。傅里叶变换红外(FTIR)研究表明,格列齐特与所使用的聚合物(TSP 和海藻酸钠)之间没有发生反应。不同配方的格列齐特负载 TSP-海藻酸钠微球在胃 pH(pH 1.2)和肠 pH(pH 7.4)中均表现出超过 12 小时的格列齐特延长体外释放曲线。研究发现,格列齐特在胃 pH 中的释放速度较慢且持续时间较长,与肠 pH 相比。这些 TSP-海藻酸钠微球还表现出良好的黏膜粘附性。在链脲佐菌素诱导的糖尿病大鼠(动物伦理委员会注册编号:IFTM/837ac/0160)的体内研究表明,所选的含有格列齐特的 TSP-海藻酸钠黏膜粘附微球制剂具有显著的降血糖作用,可通过口服给药。这种新开发的格列齐特负载 TSP-海藻酸钠黏膜粘附微球可能非常有助于格列齐特的延长全身吸收,以适当维持血糖水平并提高患者的顺应性。

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