Physicochemical characterization of zofenopril inclusion complex with hydroxypropyl-β-cyclodextrin

Abstract

Zofenopril calcium (ZOF) is one of the newest angiotensin-converting enzyme (ACE) inhibitors, highly lipophilic and with low water solubility. This research investigates the interaction between ZOF and a chemically modified derivative of β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin (HPBCD), in order to prove the formation of an inclusion complex with an enhanced water solubility profile of ZOF. In this research, for the first time, the physicochemical characterization and the solubility profile of an inclusion complex between ZOF and HPBCD are reported. Different spectroscopic techniques (UV absorption spectrometry, powder X-ray diffraction, attenuated total reflectance Fourier transform IR spectroscopy) were applied in order to prove the formation of the ZOF/HPBCD inclusion complex, both in water and in the solid state, backed by thermal analysis (TGA/DTG/HF). The obtained results confirmed that the physicochemical properties of the ZOF/HPBCD binary system, prepared using the kneading method, are different in comparison to both with the parent substances and the corresponding physical mixture, thus suggesting that an inclusion complex was formed. After the formation of the inclusion complex with HPBCD, the solubility test indicated that the water solubility of ZOF was increased 5-fold.

Solubility Enhancement of Myricetin by Inclusion Complexation with Heptakis-O-(2-Hydroxypropyl)-β-Cyclodextrin: A Joint Experimental and Theoretical Study

“…The difference in melting point indicated a decrease of thermal stability of the HP-β-CD: myricetin complex, which was the consequence of the guest amorphization through the formation of the inclusion complex [23]. Similar results were also reported for the inclusion process of other substances [24,25]. The HP-β-CD: myricetin inclusion complex showed a maximum mass loss rate at 302.65 • C lower than that of the physical mixture at 317.83 • C. The difference in melting point indicated a decrease of thermal stability of the HP-β-CD: myricetin complex, which was the consequence of the guest amorphization through the formation of the inclusion complex [23].…”

“…The difference in melting point indicated a decrease of thermal stability of the HP-β-CD: myricetin complex, which was the consequence of the guest amorphization through the formation of the inclusion complex [23]. Similar results were also reported for the inclusion process of other substances [24,25].…”

Inclusion complexes of cefuroxime axetil with β-cyclodextrin: Physicochemical characterization, molecular modeling and effect of l-arginine on complexation

“…Cyclodextrins (CDs) are cyclic oligosaccharides with hydrophobic central cavity and hydrophilic exterior, rendering them as powerful complexing and solubilizing agents [6] , [7] , [8] . They are classified into α-, β- and γ-CDs consisting of (α−1, 4)-linked six, seven and eight α- d -glucopyranose units , respectively [9] . The inclusion complexation of drug (guest) molecules with CDs (host) is an industrially feasible technique used to improve the physicochemical properties of the drug, such as solubility, dissolution rate, and bioavailability [10] , [11] , [12] .…”

“…Unfortunately, due to lower complexation efficiency (CE) of CDs, solubility enhancement via cyclodextrin (CD) complexation is limited to certain extent [13] . Several papers have reported enhancement in CE of CDs with the addition of small amounts of hydrophilic polymers [14] , [15] , hydroxyl acids [16] , [17] and/or amino acids [9] , [18] , [19] , [20] , [21] as ternary components to the complexation media resulting in the formation of ternary complexes. The basic amino acid, l -arginine (ARG), was proved to be a better choice as an auxiliary substance to increase the solubilizing capacity of CDs through electrostatic interaction and salt formation during the multi-component complex formation of weekly acidic drugs [21] , [22] .…”

Physicochemical Characterization of Febuxostat Microcomplexes with Parent and Modified Cyclodextrins

“…1,2 The inclusion phenomena of drug (guest) into the cyclodextrin (host) is the most extensively used and industrially applicable technique exploited to enhance the physicochemical properties of the guest. 3,4 CDs have been promisingly established to be the modifiable and flexible carriers in the pharmaceutical research. On the contrary, the natural parent β-cyclodextrin (βCD) have constrained the solubility and the complexation with the hydrophobic active moieties.…”