<p>Soluplus-Mediated Diosgenin Amorphous Solid Dispersion with High Solubility and High Stability: Development, Characterization and Oral Bioavailability</p>

Abstract

Background and Purpose The traditional Chinese medicine, diosgenin (Dio), has attracted increasing attention because it possesses various therapeutic effects, including anti-tumor, anti-infective and anti-allergic properties. However, the commercial application of Dio is limited by its extremely low aqueous solubility and inferior bioavailability in vivo. Soluplus, a novel excipient, has great solubilization and capacity of crystallization inhibition. The purpose of this study was to prepare Soluplus-mediated Dio amorphous solid dispersions (ASDs) to improve its solubility, bioavailability and stability. Methods The crystallization inhibition studies were firstly carried out to select excipients using a solvent shift method. According to solubility and dissolution results, the preparation methods and the ratios of drug to excipient were further optimized. The interaction between Dio and Soluplus was characterized by differential scanning calorimetry (DSC), fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), powder X-ray diffraction (PXRD) and molecular docking. The pharmacokinetic study was conducted to explore the potential of Dio ASDs for oral administration. Furthermore, the long-term stability of Dio ASDs was also investigated. Results Soluplus was preliminarily selected from various excipients because of its potential to improve solubility and stability. The optimized ASDs significantly improved the aqueous solubility of Dio due to its amorphization and the molecular interactions between Dio and Soluplus, as evidenced by dissolution test in vitro, DSC, FT-IR spectroscopy, SEM, PXRD and molecular docking technique. Furthermore, pharmacokinetic studies in rats revealed that the bioavailability of Dio from ASDs was improved about 5 times. In addition, Dio ASDs were stable when stored at 40°C and 75% humidity for 6 months. Conclusion These results indicated that Dio ASDs, with its high solubility, high bioavailability and high stability, would open a promising way in pharmaceutical applications.

Glibenclamide-Loaded Polyvinylpyrrolidone (PVP) Nanoparticles and Glibenclamide-Loaded Soluplus® Nanomicelles Intended for Parenteral Administration: Effect of Solvents Mixtures on the Electrosprayed Nanoparticles and In vitro Characterization

“…GB peaks at 1089.82 (shifted to 1091-6) and 1529 (shifted to 1531-2) cm and the polymer interaction was an extra advantage for the nanomicelles. Not only inhibit the crystallization of the drug but improved the solid solubility of the drug into the hydrophilic matrix [33]. The results were consistent with the drug release results.…”

“…Observed peaks at 1159.26, 1184.33 cm -1 and distinct sharp peaks at 1305.85, 1344.43 cm -1 are correlated with the asymmetric and symmetric stretching vibration of SO 2 [22]. The urea N-H stretching vibrations are found at 1274.99, 1620. , and C-O-C stretching at 1471.74 cm -1 [33,34]. The FTIR spectra of physical mixtures were similar to the pure GB and the individual polymer spectra, which strongly void the chemical interaction.…”

The Effects of Diosgenin on Hypolipidemia and Its Underlying Mechanism: A Review

“…Due to the poor water solubility and strong hydrophobicity of diosgenin, its oral bioavailability is not ideal, and numerous diosgenin formulation strategies have been applied to overcome these issues, including liquid crystalline (LCs) and b-cyclodextrin (b-CD) complexes, nanocrystals, and soluplus-mediated diosgenin Amorphous Solid Dispersion (ASD) technology. 103 , 104 In recent decades, ASDs have been the subject of increased research interest, as they can increase the oral bioavailability of poorly soluble drugs. 105 The aqueous solubility of optimized ASDs was significantly improved due to the amorphization of diosgenin and the molecular interactions between diosgenin and soluplus.…”

“…Hence, diosgenin ASDs, with their high solubility, high bioavailability, and high stability, represent a promising route toward pharmaceutical applications. 104 Simultaneously, although numerous preclinical studies have demonstrated that diosgenin has reliable lipid metabolism regulation function, clinical research data remain limited. Therefore, it will be necessary to verify the therapeutic effects of diosgenin on human hyperlipidemia via additional clinical trials in the future.…”

Amorphous solid dispersions of ritonavir by melt-quenching

“…Positive effect of factor A was fond on solubility, as solubility enhanced with the increase in concentration of Soluplus, which may be designated to hydrophilic nature of compound. Enhanced concentration of this carrier may impart more hydrophilicity and reduced crystallinity of the drug there by enhancing solubility of Ritonavir (Liu et al, 2020). Factor B also exerted positive effect on the initial solubility, S0.…”