α-Mangostin/γ-Cyclodextrin Inclusion Complex: Formation and Thermodynamic Study

Ine Suharyani,Khaled M Elamin,Ahmed Fouad Abdelwahab Mohammed,Muchtaridi Muchtaridi,Nasrul Wathoni,Marline Abdassah

doi:10.3390/polym13172890

Ine Suharyani, Khaled M Elamin + Show 4 more

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https://doi.org/10.3390/polym13172890

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Abstract

α-Mangostin (α-M) has various biological activities, such as anti-cancer, antibacterial, anti-fungal, anti-tyrosin, anti-tuberculosis, anti-inflammatory, and antioxidant. However, it has very low solubility in water. The formulation of this compound requires high amounts of solubilizers, which limits its clinical application. In addition, its low solubility in water is a barrier to the distribution of this drug, thus affecting its potency. Cyclodextrin (CD) is widely used as a solubility enhancer of poorly soluble drugs. This study aimed to increase the solubility of α-M in water through complex formation with CD. The complex of α-Mangostin and γ-Cyclodextrin (α-M/γ-CD CX) was prepared by the solubilization method, resulting in a solubility improvement of α-M in water. Characterization of α-M/γ-CD CX by using FTIR-Spectrometry, XRD, H-, C-, and HMBC-NMR showed that α-M was able to form an inclusion complex with γ-CD. The complex yielded an entrapment efficiency of 84.25 and the thermodynamic study showed that the α-M/γ-CD CX was formed spontaneously, based on the negative values of Gibbs energy and ΔH. Interestingly, the solubility of α-M/γ-CD CX significantly increased by 31.74-fold compared with α-M. These results suggest that α-M/γ-CD CX has the potential in the formulation of water-based preparation for clinical applications.

Highlights

Introduction αMangostin [1, 3, 6-trihydroxy-7-methoxy-2, 8-bis (3-methylbut-2-enyl) -9H-xanthen-9-one] (α-M) is a major compound in Garcinia mangostana pericarp extract (Figure 1) [1]. α-M is widely used for anti-cancer, antibacterial, anti-fungal, anti-tyrosin, anti-tuberculosis, anti-inflammatory, and antioxidant [2,3,4,5,6]
The phase solubility study was implemented to display the solubility enhancement of α-M in several concentrations of γ-CD and a Job plot predict the molar ratio of the complex formation
A phase solubility study was undertaken to analyze the molar ratio of α-M and γCD in the complex α-M/γ-CD CX was prepared by the solubilization method: α-M was dissolved in ethanol, while γ-CD was dissolved in water

Summary

Introduction

Introduction αMangostin [1, 3, 6-trihydroxy-7-methoxy-2, 8-bis (3-methylbut-2-enyl) -9H-xanthen-9-one] (α-M) is a major compound in Garcinia mangostana pericarp extract (Figure 1) [1]. α-M is widely used for anti-cancer, antibacterial, anti-fungal, anti-tyrosin, anti-tuberculosis, anti-inflammatory, and antioxidant [2,3,4,5,6]. Several studies have been undertaken to increase α-M solubility in water, with the solubility enhancement of α-M being performed by complex formation, co-solvent, or nanomicelle formation [1,7,8,9]. Α-M nanomicelles were found to increase the solubility from 0.2 ± 2 μg/mL to about 2743 ± 11 μg/mL [7]; α-M/β-CD was made with the addition of ethanol as a co-solvent, which increased the affinity of α-M to the β-CD molecule [9]; another study simulated the permeation enhancement of the α−M/β-CD and α−M/2,6-dimethyl-β-CD complex [10]. The inclusion complexes of α-M and γ-CD were prepared by solubilization method to improve the solubility of α-M in water. The termodynamic studies were implemented to study the complex formation process. α-M could be more widely used both in foαr-mMu/lγa-tCioDn, awnhdicshevhearsatlhpehsamrmallaecsotl∆ogGic[a1l];ahpopwliecvateiro, nesxpdeuriemtoentthael dinactarewasheidchsuosluebγi-liCtyDoafs αa-Mhoisnt ftohreαin-Mcluhsaiovne cnoomt ypeltexb.een reported

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