Department of Pharmaceutical Technology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt.
Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Sci Rep. 2024 Oct 18;14(1):24499. doi: 10.1038/s41598-024-74986-1.
The objective was to investigate the effect of co-administration of hydrochlorothiazide and lisinopril as fixed dose combination on their intestinal absorption. The scope was extended to enhance intestinal absorption of both drugs. In situ rabbit intestinal absorption through the duodenum and jejuno-ileum was used to monitor membrane permeability of both drugs when perfused alone or in combination. Niosomes containing glycerols (glyceroniosomes) were loaded with both drugs. Glyceroniosomes comprised Span 60 or Tween 40 in combination with cholesterol and glycerol were prepared by bath sonication. Glyceroniosomes were characterized with respect to vesicle size, drug entrapment efficiency and were examined using transmission electron microscope (TEM). The prepared vesicles were nanosized spherical vesicles with average size of 202.4 nm and 108.8 nm for span free and span containing glyceroniosomes, respectively. The recorded Zeta potential values suggested good stability of the prepared formulations. Intestinal absorption studies reflected incomplete absorption of hydrocholothiazide and lisinopril correlating with their categorization as class IV and III drugs, respectively. Co-perfusion of both drugs reduced the intestinal absorption of lisinopril. Simultaneous encapsulation in glyceroniosomes enhanced the intestinal absorption of both drugs. Tween based systems were more efficient. The study introduced glyceroniosomes as carriers of simultaneous delivery of hydrochlorothiazide and lisinopril.
目的是研究氢氯噻嗪和赖诺普利固定剂量组合给药对其肠道吸收的影响。范围扩大到增强两种药物的肠道吸收。通过十二指肠和空肠-回肠原位兔肠吸收，监测单独或联合给药时两种药物的膜通透性。含有甘油的尼奥斯omes（甘油尼奥斯omes）负载两种药物。甘油尼奥斯omes 由 Span 60 或 Tween 40 与胆固醇和甘油组成，通过浴超声处理制备。甘油尼奥斯omes 对囊泡大小、药物包封效率进行了特征化，并使用透射电子显微镜（TEM）进行了检查。制备的囊泡为纳米级球形囊泡，无 Span 的囊泡平均粒径为 202.4nm，含 Span 的囊泡平均粒径为 108.8nm。记录的 Zeta 电位值表明制备的制剂具有良好的稳定性。肠道吸收研究反映了氢氯噻嗪和赖诺普利不完全吸收，这与它们分别归类为第四类和第三类药物有关。两种药物的同时灌注减少了赖诺普利的肠道吸收。同时包封在甘油尼奥斯omes 中增强了两种药物的肠道吸收。基于吐温的系统更有效。该研究介绍了甘油尼奥斯omes 作为氢氯噻嗪和赖诺普利同时传递的载体。
