Enhanced solubility of guanosine by inclusion complexes with cyclodextrin derivatives: Preparation, characterization, and evaluation

Mohandoss, Sonaimuthu; Atchudan, Raji; Edison, Thomas Nesakumar Jebakumar Immanuel; Mandal, Tapas K.; Palanisamy, Subramanian; You, SangGuan; Napoleon, Ayyakannu Arumugam; Shim, Jae‐Jin; Lee, Yong Rok

doi:10.1016/j.carbpol.2019.115166

Cited by 56 publications

(21 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pure Frax ( Figure 3(E,a) ) appeared as rod-like particles, while β-CD exhibited in a larger form ( Figure 3(E,b) ). Consistent with previous studies, pure HP-β-CD, G 2 -β-CD, and SBE-β-CD were spherical with cavity-containing structures ( Figure 3(E,c–e) ) (Mohandoss et al., 2019 ). The morphology of Frax changed when it formed CDs-Frax complexes.…”

Section: Resultssupporting

confidence: 91%

Rational formulation engineering of fraxinellone utilizing 6-O-α-D-maltosyl-β-cyclodextrin for enhanced oral bioavailability and hepatic fibrosis therapy

Feng

Yang

et al. 2021

Drug Delivery

View full text Add to dashboard Cite

Although Fraxinellone (Frax) isolated from Dictamnus albus L. possessed excellent anti-hepatic fibrosis activity, oral administration of Frax suffered from the inefficient therapeutic outcome in vivo due to negligible oral absorption. At present, the oral formulation of Frax is rarely exploited. For rational formulation design, we evaluated preabsorption risks of Frax and found that Frax was rather stable while poorly dissolved in the gastrointestinal tract (78.88 μg/mL), which predominantly limited its oral absorption. Further solubility test revealed the outstanding capacity of cyclodextrin derivatives (CDs) to solubilize Frax (6.8–12.8 mg/mL). This led us to study the inclusion complexes of Frax with a series of CDs and holistically explore their drug delivery performance. Characterization techniques involving 1 H-NMR, FT-IR, DSC, PXRD, and molecular docking confirmed the most stable binding interactions when Frax complexed with 6-O-α-D-maltosyl-β-cyclodextrin (G 2 -β-CD-Frax). Notably, G 2 -β-CD-Frax exhibited the highest solubilizing capacity, fast dissolution rate, and superior Caco-2 cell internalization with no obvious toxicity. Pharmacokinetic studies demonstrated markedly higher oral bioavailability of G 2 -β-CD-Frax (5.8-fold that of free drug) than other Frax-CDs. Further, long-term administration of G 2 -β-CD-Frax (5 mg/kg) efficiently inhibited CCl 4 -induced hepatic fibrosis in the mouse without inducing any toxicity. Our results will inspire the continued advancement of optimal oral Frax formulations for anti-fibrotic therapy.

show abstract

Section: Resultssupporting

confidence: 91%

Rational formulation engineering of fraxinellone utilizing 6-O-α-D-maltosyl-β-cyclodextrin for enhanced oral bioavailability and hepatic fibrosis therapy

Feng

Yang

et al. 2021

Drug Delivery

View full text Add to dashboard Cite

show abstract

“…The β-CD showed two endothermic events between 63.80–142.16 °C, and 308.71–343.18 °C. The first endothermic event is related to the loss of water and the second event is related to its melting peak [ 19 ], similar to results obtained by other studies [ 18 , 22 , 23 , 24 ].…”

Section: Resultssupporting

confidence: 81%

“…Only with the use of β-CD it was possible to observe an increase in the percentage of ICaf dissolved in the medium in relation to pure ICaf, reaching approximately 70% of release in the initial 5 min. The passage of the drug from the crystalline form to the amorphous state is a factor that generally makes the systems more soluble, presenting a higher dissolution rate [ 24 ]. The change in the morphology of ICaf when complexed ICaf:β-CD (1:1) was already evidenced in the SEM micrographs discussed above.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

β-Cyclodextrin/Isopentyl Caffeate Inclusion Complex: Synthesis, Characterization and Antileishmanial Activity

et al. 2020

View full text Add to dashboard Cite

Isopentyl caffeate (ICaf) is a bioactive ester widely distributed in nature. Our patented work has shown promising results of this molecule against Leishmania. However, ICaf shows poor solubility, which limits its usage in clinical settings. In this work, we have proposed the development of an inclusion complex of ICaf in β-cyclodextrin (β-CD), with the aim to improve the drug solubility, and thus, its bioavailability. The inclusion complex (ICaf:β-CD) was developed applying three distinct methods, i.e., physical mixture (PM), kneading (KN) or co-evaporation (CO) in different molar proportions (0.25:1, 1:1 and 2:1). Characterization of the complexes was carried out by thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and molecular docking. The ICaf:β-CD complex in a molar ratio of 1:1 obtained by CO showed the best complexation and, therefore, was selected for further analysis. Solubility assay showed a marked improvement in the ICaf:β-CD (CO, 1:1) solubility profile when compared to the pure ICaf compound. Cell proliferation assay using ICaf:β-CD complex showed an IC50 of 3.8 and 2.7 µg/mL against L. amazonesis and L. chagasi promastigotes, respectively. These results demonstrate the great potential of the inclusion complex to improve the treatment options for visceral and cutaneous leishmaniases.

show abstract

“…At present, most widely used drugs, natural products, and drug candidates are insoluble in water, and increasing the solubility of poorly soluble drugs is an important problem for many drug molecules [1][2][3]. Several strategies have been studied to overcome this problem, such as salt formation [4][5][6], nanoparticles [7][8][9][10], inclusion complexes [11], liposomes [12,13], and amorphous solid dispersions [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Mechanism and Improved Dissolution of Glycyrrhetinic Acid Solid Dispersion by Alkalizers

et al. 2020

View full text Add to dashboard Cite

The purpose of this study was to increase the dissolution of glycyrrhetinic acid (GA) by preparing ternary solid dispersion (TSD) systems containing alkalizers, and to explore the modulating mechanism of alkalizers in solid dispersion systems. GA TSDs were prepared by hot melt extrusion (HME) with Kollidon® VA64 as the carrier and L-arginine/meglumine as the alkalizers. The in vitro release of the TSD was investigated with a dissolution test, and the dissociation constant (pKa) was used to describe the ionization degree of the drug in different pH buffers. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier Transform Infrared Spectroscopy (FTIR), Raman spectra, X-ray photoelectron spectroscopy (XPS), and a molecular model were used for solid-state characterizations and to study the dissolution mechanism of the TSDs. It was evident that the dissolution of GA significantly increased as a result of the TSD compared to the pure drug and binary solid dispersion. SEM, DSC, and XPRD data showed that GA transformed into an amorphous form in TSD. As illustrated by FTIR, Raman, XPS, and molecular docking, high binding energy ion-pair complexes formed between GA and the alkalizers during the process of HME. These can destroy the H-bond between GA molecules. Further, intermolecular H-bonds formed between the alkalizers and Kollidon® VA64, which can increase the wettability of the drug. Our results will significantly improve the solubility and dissolution of GA. In addition, the lower pKa value of TSD indicates that higher ionization is beneficial to the dissolution of the drug. This study should facilitate further developments of TSDs containing alkalizers to improve the dissolution of weakly acidic drugs and gain a richer understanding of the mechanism of dissolution.

show abstract

Enhanced solubility of guanosine by inclusion complexes with cyclodextrin derivatives: Preparation, characterization, and evaluation

Cited by 56 publications

References 52 publications

Rational formulation engineering of fraxinellone utilizing 6-O-α-D-maltosyl-β-cyclodextrin for enhanced oral bioavailability and hepatic fibrosis therapy

Rational formulation engineering of fraxinellone utilizing 6-O-α-D-maltosyl-β-cyclodextrin for enhanced oral bioavailability and hepatic fibrosis therapy

β-Cyclodextrin/Isopentyl Caffeate Inclusion Complex: Synthesis, Characterization and Antileishmanial Activity

Mechanism and Improved Dissolution of Glycyrrhetinic Acid Solid Dispersion by Alkalizers

Contact Info

Product

Resources

About