Abstract
This research investigates the interaction between fosinopril sodium (FOS) and beta-cyclodextrin (β-CD) in aqueous solution and in solid state, in order to prove the formation of an inclusion complex between the two components. The stoichiometry of the inclusion complex was found as 1 : 1 by employing continuous variation method in UV. The formation constant was calculated as 278.93 M−1using Benesi-Hildebrand equation. The kneaded product (KP) and the physical mixture (PM) were further experimentally examined, using FTIR, powder X-ray diffractometry, and thermal analysis. The results confirm that the physicochemical properties of the FOS/β-CD KP are different from FOS and that the kneading method leads to formation of solid state inclusion complex between FOS andβ-CD. Structural studies of the FOS/β-CD were carried out using molecular modeling techniques, in order to explain the complexation mechanism and the host-guest geometry.
Highlights
Cyclodextrins are cyclic oligosaccharides that have the ability to form inclusion complexes with small molecules or with hydrophobic moiety of larger molecules [1]. β-CD is the heptacyclic oligomer of glucose, having the smallest water solubility at 25∘C from all natural cyclodextrins
Taking into account the deduced interactions between βCD and fosinopril sodium (FOS), involving distant parts of FOS and the results presented in Section 3.7, it cannot be excluded that complexes with favorable energies and different geometries are present in the kneaded product
The experimental results indicated that a real inclusion complex was formed between FOS and β-CD when the kneading preparation method was applied, with a 1 : 1 stoichiometry, as determined by Job’s technique
Summary
Cyclodextrins are cyclic oligosaccharides that have the ability to form inclusion complexes with small molecules or with hydrophobic moiety of larger molecules [1]. β-CD is the heptacyclic oligomer of glucose, having the smallest water solubility at 25∘C from all natural cyclodextrins. Β-CD is the heptacyclic oligomer of glucose, having the smallest water solubility at 25∘C from all natural cyclodextrins. Β-CD is the most used natural cyclodextrin in pharmaceutical applications, due to its properties which allow for increasing the drug solubility in aqueous solution, improving the bioavailability, masking the inappropriate organoleptic properties such as odor or taste, protecting the included substance from oxidation, and losing through volatilization. Fosinopril sodium, chemically named sodium (2S,4S)4-cyclohexyl-1-(2-{[2-methyl-1-(propanoyloxy)propoxy](4phenylbutyl)phosphoryl}acetyl)pyrrolidine-2-carboxylate (presented in Figure 1(a)), is the only phosphinic acid derivative among the angiotensin converting enzyme (ACE) inhibitors class. It is used for the treatment of essential hypertension, congestive heart failure, diabetic nephropathy, and postmyocardial infarction [5].
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