Preparation and Evaluation of Diosgenin Nanocrystals to Improve Oral Bioavailability

Abstract

Diosgenin (DSG), a well-known steroid sapogenin derived from Dioscorea nipponica Makino and Dioscorea zingiberensis Wright, has a variety of bioactivities. However, it shows low oral bioavailability due to poor aqueous solubility and strong hydrophobicity. The present study aimed to develop DSG nanocrystals to increase the dissolution and then improve the oral bioavailability and biopharmaceutical properties of DSG. DSG nanocrystals were prepared by the media milling method using a combination of pluronic F127 and sodium dodecyl sulfate as surface stabilizers. The physicochemical properties of the optimal DSG nanocrystals were characterized using their particle size distribution, morphology, differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy data, and solubility and dissolution test results. Pharmacokinetic studies of the DSG coarse suspension and its nanocrystals were performed in rats. The particle size and polydispersity index of DSG nanocrystals were 229.0 ± 3.7 nm and 0.163 ± 0.064, respectively. DSG retained its original crystalline state during the manufacturing process, and its chemical structure was not compromised by the nanonizing process. The dissolution rate of the freeze-dried DSG nanocrystals was significantly improved in comparison with the original DSG. The pharmacokinetic studies showed that the AUC and C of DSG nanocrystals increased markedly (p< 0.01) in comparison with the DSG coarse suspension by about 2.55- and 2.01-fold, respectively. The use of optimized nanocrystals is a good and efficient strategy for oral administration of DSG due to the increased dissolution rate and oral bioavailability of DSG nanocrystals.

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

“…The samples were taken orally at a single intragastric dose of Dio (100 mg/kg body weight). The dosage was determined according to literature 20 and through preliminary experiments. Heparinized plasma samples (0.4 mL) were collected from the ophthalmic veins using sterile capillary tube before administration and at 0.083, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 h post-administration.…”

Spice-Derived Bioactive Ingredients: Potential Agents or Food Adjuvant in the Management of Diabetes Mellitus

“…Interestingly, some methods are available to improve the bioavailability of diosgenin, although not directly investigated in any diabetic model. The use of diosgenin and β-cyclodextrin inclusion complex, deglycosylation of diosgenin and diosgenin nanocrystals are receiving much attention in the recent years (Gao et al, 2012 ; Okawara et al, 2013 , 2014 ; Liu et al, 2016 ). For instance, the use of diosgenin and β-cyclodextrin inclusion complexes improved the bioavailability of diosgenin by 45% in rats (Okawara et al, 2013 ).…”

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

“…In addition, the bioavailability of DG has been further improved by combining β-CD and liquid crystal DG to enhance the bioavailability of poorly water-soluble drugs [34]. Recently, DG nanocrystals have been prepared via a media-milling method using a combination of pluronic F127 and sodium dodecyl sulfate as surface stabilizers, resulting in a significant improvement in the dissolution rate and pharmacokinetic profile compared to DG alone as well as increased bioavailability of DG [60]. An eight-arm-PEG-DG conjugate has been prepared for hydrophobic drug delivery via self-assembly to nanoparticles [61].…”