Glyceroniosomes for enhanced intestinal absorption of hydrochlorothiazide and lisinopril in their fixed dose combination

• Published in: Scientific reports 2024-10, Vol.14 (1), p.24499-14, Article 24499
• Main Authors: Elbasuony, Aya R., Abdelaziz, Abdelaziz E., Mazyed, Eman A., El Maghraby, Gamal M.
• Format: Article
• Language: English
• Subjects: 631/154/433; 639/925/352/152; Absorption; Animals; Cholesterol; Drug Combinations; Drug delivery; Drug dosages; Drugs; Duodenum; Fixed dose combination; Glycerol - chemistry; Glyceroniosome; Humanities and Social Sciences; Hydrochlorothiazide; Hydrochlorothiazide - administration & dosage; Hydrochlorothiazide - chemistry; Hydrochlorothiazide - pharmacokinetics; Ileum; In situ intestinal perfusion; Intestinal absorption; Intestinal Absorption - drug effects; Intestine; Liposomes; Lisinopril; Lisinopril - administration & dosage; Lisinopril - pharmacokinetics; Male; Membrane permeability; multidisciplinary; Rabbits; Science; Science (multidisciplinary); Sonication; Vesicles; Zeta potential
• ISSN: 2045-2322; 2045-2322
• 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.